Short-term cost-effectiveness of one-stage implant-based breast reconstruction with an acellular dermal matrix versus two-stage expander-implant reconstruction from a multicentre randomized clinical trial.

BACKGROUND: Implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure and its economic impact is significant. This study aimed to analyse whether a direct one-stage IBBR with use of an acellular dermal matrix (ADM) is more cost-effective than two-stage (expander-implant) breast reconstruction. METHODS: The BRIOS (Breast Reconstruction In One Stage) study was an open-label multicentre RCT in which women scheduled for skin-sparing mastectomy and immediate IBBR were randomized between one-stage IBBR with ADM or two-stage IBBR. Duration of surgery and hospital stay, and visits for the primary surgery, unplanned and cosmetic procedures were recorded. Costs were estimated at an institutional level. Health status was assessed by means of the EuroQol Five Dimensions 5L questionnaire. RESULTS: Fifty-nine patients (91 breasts) underwent one-stage IBBR with ADM and 62 patients (92 breasts) two-stage IBBR. The mean(s.d.) duration of surgery in the one-stage group was significantly longer than that for two-stage IBBR for unilateral (2·52(0·55) versus 2·02(0·35) h; P < 0·001) and bilateral (4·03(1·00) versus 3·25(0·58) h; P = 0·017) reconstructions. Costs were higher for one-stage compared with two-stage IBBR for both unilateral (€12 448 (95 per cent c.i. 10 722 to 14 387) versus €9871 (9373 to 10 445) respectively; P = 0·025) and bilateral (€16 939 (14 887 to 19 360) versus €13 383 (12 414 to 14 669); P = 0·002) reconstructions. This was partly related to the use of relatively expensive ADM. There was no difference in postoperative health status between the groups. CONCLUSION: One-stage IBBR with ADM was associated with higher costs, but similar health status, compared with conventional two-stage IBBR. Registration number: NTR5446 ( http://www.trialregister.nl).

Toll-Like Receptors (TLRs) Expression in Contracted Capsules Compared to Uncontracted Capsules.

INTRODUCTION: The etiology of capsular contracture after surgical implantation of breast implants remains unclear, but an important role is seen for the immune system. Toll-like receptors are immune receptors recognizing both pathogen-associated molecular patterns and damage-associated molecular patterns. The former are present on bacteria such as Staphylococcus epidermidis (bacteria earlier associated with capsular contracture), and the latter are released after (mechanical) stress. The aim of this study was to investigate the expression of TLRs 1-10 in relation to capsular contracture. MATERIALS AND METHODS: Fifty consecutive breast capsules were collected during implant removal or replacement. The extent of capsular contracture was scored according to the Baker score. A sample specimen (0.5 cm3) was obtained from all tissues. cDNA was synthesized from isolated mRNA from the collected specimens. PCR analyses were conducted to test for cDNA presence and to quantify concentration. TLR1-10 expression was measured for each of the Baker scores separately and compared to all Baker scores. RESULTS: Expression of all TLRs in all Baker scores was seen. TLR2 and TLR6 were more often present in contracted samples (Baker 3 or 4) compared to uncontracted samples (Baker 1 or 2) [Baker 2 vs. 3 (p = 0.034) and Baker 2 vs. 3 (p = 0.003), respectively]. None of the TLRs displayed a significantly higher expression in contracted capsules compared to uncontracted capsules. CONCLUSION: This study shows that TLR2 and TLR6 are more often expressed in contracted capsules compared to non-contracted capsules however not in higher concentrations. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Predictors of complications after direct-to-implant breast reconstruction with an acellular dermal matrix from a multicentre randomized clinical trial.

BACKGROUND: In the multicentre randomized trial BRIOS (Breast Reconstruction In One Stage), direct-to-implant (DTI) breast reconstruction with an acellular dermal matrix (ADM) was associated with a markedly higher postoperative complication rate compared with two-stage tissue expander/implant breast reconstruction. This study aimed to identify factors that contribute to the occurrence of complications after DTI ADM-assisted breast reconstruction. METHODS: Data were obtained from the BRIOS study, including all patients treated with DTI ADM-assisted breast reconstruction. Logistic regression analyses were performed to identify factors predictive of postoperative complications. RESULTS: Fifty-nine patients (91 breasts) were included, of whom 27 (35 breasts) developed a surgical complication. Reoperations were performed in 29 breasts (32 per cent), with prosthesis removal in 22 (24 per cent). In multivariable analyses, mastectomy weight was associated with complications (odds ratio (OR) 1·94, 95 per cent c.i. 1·33 to 2·83), reoperations (OR 1·70, 1·12 to 2·59) and removal of the implant (OR 1·55, 1·11 to 2·17). Younger patients (OR 1·07, 1·01 to 1·13) and those who received adjuvant chemotherapy (OR 4·83, 1·15 to 20·24) more frequently required reoperation. In univariable analyses, adjuvant radiotherapy showed a trend towards more complications (OR 7·23, 0·75 to 69·95) and removal of the implant (OR 5·12, 0·76 to 34·44), without reaching statistical significance. CONCLUSION: Breast size appeared to be the most significant predictor of complications in DTI ADM-assisted breast reconstruction. The technique should preferably be performed in patients with small to moderate sized breasts. Registration number: NTR5446 ( http://www.trialregister.nl).

The Histological Composition of Capsular Contracture Focussed on the Inner Layer of the Capsule: An Intra-Donor Baker-I Versus Baker-IV Comparison.

BACKGROUND: Capsular contracture remains one of the major complications after breast implantation surgery. The extent of capsular contraction is scored using the Baker scale. The aim of this study was to compare intra-individual Baker-I with Baker-IV capsules, and in particular the prevalence and histological properties of the inner capsule layer. METHODS: Twenty capsules from ten patients were included after bilateral explantation surgery due to unilateral capsular contracture (Baker-IV) after cosmetic augmentation with textured implants. All capsules underwent (immune-)histochemical analysis: haematoxylin-eosin (morphology), CD68 (macrophages), cytokeratin (epithelial cells) and vimentin (fibroblasts), and were visually scored for cell density and the presence of an inner layer and measured for thickness. RESULTS: Baker-IV (n = 10) capsules were significantly thicker compared to Baker-I (n = 10) capsules (P = 0.004). An inner layer was present in 8 Baker-I capsules. All Baker-I capsules were vimentin and CD68-positive and cytokeratin-negative. Positive vimentin was seen throughout the inner layer, and CD-68 staining was observed adjacent to the intermediate capsule layer. In contrast, only 2 Baker-IV capsules had an inner layer, of which only 1 showed the same profile as Baker-I capsules (P = 0.016). No cytokeratin positivity was seen in any capsule. In Baker-IV capsules, outer layers showed more positivity for both vimentin and CD68. CONCLUSION: The inner layer is morphologically consistent with synovial metaplasia and is more prevalent in healthy, uncontracted Baker-I capsules. This inverse relation between the presence of the inner layer and higher Baker classification or pathological contracture could indicate a protective role of the inner layer against capsular contracture formation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluation of the nutritional status of older hospitalised geriatric patients: a comparative analysis of a Mini Nutritional Assessment (MNA) version and the Nutritional Risk Screening (NRS 2002).

BACKGROUND: The present study aimed to evaluate a short-form (MNA-SF) version of the Mini Nutritional Assessment (MNA), in which some of the items were operationalised, based on scores from tools used for a comprehensive geriatric assessment, as a method for analysing the nutritional status of hospitalised geriatric patients. We compared this MNA-SF version with the corresponding MNA long-form (MNA-LF) and Nutritional Risk Screening 2002 (NRS 2002) in terms of completion rate, prevalence and agreement regarding malnutrition and/or the risk of this. METHODS: In total, 201 patients aged ≥65 years who were hospitalised in geriatric wards were included in this analysis. RESULTS: The MNA-SF, MNA-LF and NRS 2002 were completed in 98.0%, 95.5% and 99.5% of patients (P = 0.06), respectively. The MNA-SF, MNA-LF and NRS 2002 categorised 93.4%, 91.1% and 66.0% of patients as being malnourished or at risk of being malnourished (P < 0.001). Agreement between the MNA-SF and MNA-LF was substantial (κ = 0.70, P < 0.001). No agreement between the MNA-SF and NRS 2002 was found (κ = -0.12, P < 0.001). Interestingly, NRS 2002 part 1 (prescreening) revealed a false negative rate of 21.0% (only in patients aged ≥70 years who showed moderate disease severity) in relation to the NRS 2002 part 2. CONCLUSIONS: The MNA-SF version emerged as a useful tool for evaluating the nutritional status of hospitalised geriatric patients. The NRS 2002 part 1 showed limited value as a prescreening aid in relation to the NRS 2002 part 2 in the same group of patients.

Revealing the impact of local access-site complications and upper extremity dysfunction post transradial percutaneous coronary procedures.

OBJECTIVES: Little is known about local access-site complications and upper extremity dysfunction after transradial percutaneous coronary procedures (TR-PCP). This systematic review study aimed to summarise the current knowledge on the incidences of access-site complications and upper extremity dysfunction after TR-PCP. METHODS: Two independent, trained investigators searched MEDLINE, EMBASE and CENTRAL for eligible studies published before 1 January 2015. Also, they hand-searched the conference proceedings of the annual scientific sessions of the American College of Cardiology, the American Heart Association, European Society of Cardiology, and the Trans-catheter Cardiovascular Therapeutics. Inclusion criteria were cohort studies and clinical trials discussing the incidence of access-site complications and upper extremity function after transradial percutaneous coronary intervention (TR-PCI) and/or transradial coronary angiography (TR-CAG) as endpoints. RESULTS: 176 articles described access-site complications. The incidence is up to 9.6 %. Fourteen articles described upper extremity dysfunction, with an incidence of up to 1.7 %. Upper extremity dysfunction was rarely investigated, hardly ever as primary endpoint, and if investigated not thoroughly enough. CONCLUSION: Upper extremity dysfunction in TR-PCP has never been properly investigated and is therefore underestimated. Further studies are needed to investigate the magnitude, prevention and best treatment of upper extremity dysfunction. Optimising TR-PCP might be achieved by using slender techniques, detection of upper extremity dysfunction and early referral to a hand rehabilitation centre.

MRI screening for silicone breast implant rupture: accuracy, inter- and intraobserver variability using explantation results as reference standard.

OBJECTIVES: The recall of Poly Implant Prothèse (PIP) silicone breast implants in 2010 resulted in large numbers of asymptomatic women with implants who underwent magnetic resonance imaging (MRI) screening. This study's aim was to assess the accuracy and interobserver variability of MRI screening in the detection of rupture and extracapsular silicone leakage. METHODS: A prospective study included 107 women with 214 PIP implants who underwent explantation preceded by MRI. In 2013, two radiologists blinded for previous MRI findings or outcome at surgery, independently re-evaluated all MRI examinations. A structured protocol described the MRI findings. The ex vivo findings served as reference standard. RESULTS: In 208 of the 214 explanted prostheses, radiologists agreed independently about the condition of the implants. In five of the six cases they disagreed (2.6 %), but subsequently reached consensus. A sensitivity of 93 %, specificity of 93 %, positive predictive value of 77 % and negative predictive value of 98 % was found. The interobserver agreement was excellent (kappa value of 0.92). CONCLUSIONS: MRI has a high accuracy in diagnosing rupture in silicone breast implants. Considering the high kappa value of interobserver agreement, MRI appears to be a consistent diagnostic test. A simple, uniform classification, may improve communication between radiologist and plastic surgeon. KEY POINTS: MRI has a high accuracy in diagnosing rupture in silicone breast implants. MRI appears to be a consistent diagnostic test with excellent interobserver agreement. A simple, uniform classification system, improves communication between radiologist and plastic surgeon. The interobserver agreement on implant rupture is higher than on extracapsular leakage.

Change in augmentation index during NOS inhibition, an index of basal NO production, is an independent determinant of large-artery function.

BACKGROUND/AIMS: Arterial wave reflection, measured as augmentation index (AIx), and central pulse pressure (PP) closely predict cardiovascular events. We hypothesized that basal nitric oxide (NO) production would be a determinant of AIx and central PP. METHODS: AIx and central PP were assessed at baseline by pulse wave analysis in 86 male subjects across a wide range of age, blood pressure and lipid values. The basal NO production in the cardiovascular system was then determined as change in AIx during NO synthase blockade with N(G)-monomethyl-L-arginine (L-NMMA, 3.25 mg/kg). RESULTS: AIx increased from 17.5 ± 14.6 to 23.1 ± 14.2 during L-NMMA infusion (p < 0.001). The increase in AIx during NO synthase blockade, an index of basal NO production, was inversely related to baseline central AIx and PP, and positively to PP amplification. Multiple linear regression analyses disclosed that in addition to age and mean blood pressure, change of AIx to L-NMMA is a strong and independent determinant of baseline central AIx, central PP and PP amplification. CONCLUSION: Greater change of AIx to L-NMMA, an index of basal NO production, is associated with better large-artery function. Therefore, therapeutic interventions which increase the basal NO production might be particularly effective in reducing cardiovascular risk.

The Influence of Body Contouring Surgery on Weight Control and Comorbidities in Patients After Bariatric Surgery.

INTRODUCTION: A considerable number of patients experience some long-term weight regain after bariatric surgery. Body contouring surgery (BCS) is thought to strengthen post-bariatric surgery patients in their weight control and maintenance of achieved improvements in comorbidities. OBJECTIVES: To examine the impact of BCS on long-term weight control and comorbidities after bariatric surgery. METHODS: We performed a retrospective study in a prospective database. All patients who underwent primary Roux-en-Y gastric bypass (RYGB) and presented for preoperative consultation of BCS in the same hospital were included in the study. Linear and logistic mixed-effect model analyses were used to evaluate the longitudinal relationships between patients who were accepted or rejected for BCS and their weight loss outcomes or changes in comorbidities. RESULTS: Of the 1150 patients who underwent primary RYGB between January 2010 and December 2014, 258 patients (22.4%) presented for preoperative consultation of BCS. Of these patients, 126 patients eventually underwent BCS (48.8%). Patients who were accepted for BCS demonstrated significant better ∆body mass index (BMI) on average over time (- 1.31 kg/m2/year, 95% confidence interval (CI) -2.52 - -0.10, p = 0.034) and percent total weight loss (%TWL) was significantly different at 36 months (5.79, 95%CI 1.22 - 10.37, p = 0.013) and 48 months (6.78, 95%CI 0.93 - 12.63, p = 0.023) after body contouring consultation. Patients who were accepted or rejected did not differ significantly in the maintenance of achieved improvements in comorbidities. CONCLUSION: BCS could not be associated with the maintenance of achieved improvements in comorbidities after bariatric surgery, whereas it could be associated with improved weight loss maintenance at 36 and 48 months after body contouring consultation. This association should be further explored in a large longitudinal study.

Long-Term Results of Universal 2 Total Wrist Arthroplasty.

Background The Universal 2 is a widely used total wrist implant that aims to maintain function of the wrist. Purpose Promising mid-term results of the Universal 2 total wrist implant are described in the literature. This study evaluates the long-term results in terms of implant survival and patient satisfaction. Patients and Methods Patients who received a Universal 2 implant between 2004 and 2009 were retrospectively identified through a database search. Clinical outcome and complications of the implant were assessed by examination of the patient's medical records, X-rays, and a questionnaire, consisting of the Patient-Rated Wrist and Hand Evaluation questionnaire (PRWHE) and Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaires and additional questions. Results Twenty-five patients (26 wrists) were included in this study. Twenty-one (81%) Universal 2 implants remained in situ after a mean follow-up of 11 years. Moderate PRWHE (44) and QuickDASH (41) scores were found in these cases. Five Universal 2 implants failed and were converted to a total wrist arthrodesis after a mean period of 9.2 years due to distal component loosening ( n = 3), recurrent luxation ( n = 1), or recurrent synovitis ( n = 1). Twenty-three (92%) patients were (very) satisfied with the Universal 2 implant. Conclusion The Universal 2 demonstrates a high (81%) implant survival with a high patient satisfaction after a mean follow-up of 11 years. Prospective studies of the Universal 2 implant are necessary to objectify improvement in wrist function and to provide a better comparison to other fourth generation wrist implants.

Poly Implant Prothèse silicone breast implants: implant dynamics and capsular contracture.

BACKGROUND: The Poly Implant Prothèse (PIP) implants were withdrawn from the market in 2010 due to the use of low-grade silicone, causing a high risk for implant rupture. The aim of this study was to investigate the implant dynamics of PIP breast implants, as well as to determine the rate and predictors of implant gel bleeding, rupture, and capsular contracture in PIP implants. METHODS: Eighty women with a total of 152 PIP implants who underwent a reoperation in 2012 were enrolled in this study. Physical investigation included assessing the Baker score and demographics were retrospectively traced in medical records. The pre- and post-operative volumes of the implants were calculated and their state was determined intraoperatively by the surgeon. RESULTS: The implants were removed after a mean implant duration of 11 ± 2.1 years. Gel bleed and implant rupture occurred in respectively 42 and 25% of the implants. Intact implants had post-operative volume increase as well as decrease. There was a correlation between gel bleeding and more post-operative implant volume increase (P ≤ 0.05). Capsular contracture had a protective effect against post-operative implant volume increase (P ≤ 0.05), while a post-operative implant volume increase provided a protective influence in developing capsular contracture (P ≤ 0.05). Additionally, implant rupture led to a higher risk of capsular contracture (P ≤ 0.05). CONCLUSIONS: We managed to illustrate that PIP implant shells were too permeable and that there is a correlation between gel bleeding and the increase of the post-operative implant volume. Implant rupture led to a higher risk for developing capsular contracture.Level of evidence: Level III, risk / prognostic study.

High-Technology Based Gait Assessment in Frail People: Associations between Spatio-Temporal and Three-Dimensional Gait Characteristics with Frailty Status across Four Different Frailty Measures.

OBJECTIVE: We analyzed associations between a battery of gait characteristics and frailty status across four different frailty instruments in old patients. DESIGN: Cross-sectional study. SETTING: Geriatric wards of a general hospital. PARTICIPANTS: 123 hospitalized patients aged ≥65 years. MEASUREMENTS: Spatio-temporal and three-dimensional gait characteristics were assessed by an electronic walkway and a shoe-mounted, inertial sensor-based mobile gait analysis system. Frailty status was assessed by the frailty phenotype (FP), Clinical Frailty Scale (CFS), frailty index (FI), and frailty index based on a comprehensive geriatric assessment (FI-CGA). RESULTS: A reduction in walking speed (FP, FI, FI-CGA), stride length (FP, FI, FI-CGA), maximum toe clearance (FP, CFS, FI, FI-CGA), toe off angle (FP, CFS, FI, FI-CGA), heal strike angle (FI-CGA) and greater stride length variability (FP, CFS, FI, FI-CGA), stride time variability (FP, FI), double support time (FP, FI), and stride width (CFA, FI-CGA) were associated with frailty status across the four frailty instruments (all P < 0.05, respectively). Walking speed (FP, CFS, FI, FI-CGA), stride length (FP, CFS, FI, FI-CGA), maximum toe clearance (FP, CFS, FI, FI-CGA), toe off angle (FP, CFS, FI, FI-CGA), heal strike angle (FP, FI), stride length variability (CFS, FI, FI-CGA), stride time variability (FI), double support time (FP), and stride width (FP, CFS, FI) were related with frailty severity across the four frailty instruments independent of age and sex (all P adjusted < 0.05, respectively). CONCLUSIONS: Gait changes in frail patients include more than solely a reduction in walking speed.

Prediction of one-year mortality by five different frailty instruments: A comparative study in hospitalized geriatric patients.

BACKGROUND: Data comparing the ability of different major frailty instruments for predicting mortality in hospitalized geriatric patients are scare. MATERIAL AND METHODS: 307 patients ≥65years who were hospitalized on geriatric wards were included in this prospective analysis. A fifty-item frailty index (FI), a ten-domain+co-morbidity frailty index based on a standardized comprehensive geriatric assessment (FI-CGA), the nine category Clinical Frailty Scale (CFS-9), the CSHA rules-based frailty definition (CSHA-RBFD), and the frailty phenotype (FP) were assessed during the patients' hospital stays. Patients were followed up over a one-year period. RESULTS: Follow-up data after one year could be obtained from 305 out of the 307 participants. Sixty two participants (20.3%) had died after that time. The FI, FI-CGA, CFS-9, CSHA-RBFD, and FP could all discriminate between patients who died and those who survived during follow-up (areas under the ROC curves: 0.805, 0.808, 0.852, 0.703 and 0.757, all P<0.001, respectively). The CFS-9 showed a better discriminative ability for one-year mortality compared to the FI, FI-CGA, CSHA-RBFD, and FP (all P<0.05, respectively). The FI and the FI-CGA did not differ in their discriminative ability for one-year mortality (P=0.440). The CSHA-RBFD and the FP demonstrated a comparable discriminative ability (P=0.241) and, when compared to the CFS-9, FI, and FI-CGA, an inferior discriminative ability for one-year mortality (all P<0.05, respectively). CONCLUSION: Among those frailty instruments that were evaluated, the CFS-9 emerged as the most powerful for prediction of one-year mortality.

Management of lunotriquetral instability: a review of the literature.

UNLABELLED: Lunotriquetral ligament injury is a relatively common cause of ulnar-sided wrist pain. Injury ranges from partial stable ligament tears to extensive perilunate instability. Clinical decision-making largely depends on the chronicity, instability and cause of the ligament injury. Conservative treatment is generally regarded as first choice of treatment of mild lunotriquetral instability; however, outcome studies on conservative treatment are lacking. Temporary arthroscopic pinning and/or debridement are minimally invasive procedures of preference. In the case of more dissociative injury, surgical interventions may be performed. The literature suggests that soft tissue reconstruction is an effective procedure in this group. Arthrodesis of the lunotriquetral joint is associated with high rates of non-union (up to 57%) and the indications for surgery should therefore be very clear. Methodological issues make it hard to draw firm conclusions from the data. Studies on the effectiveness of conservative management and prospective comparative studies will further improve clinical decision-making in lunotriquetral instability. LEVEL OF EVIDENCE: N/A.

A comparison of Frailty Indexes Based on a Comprehensive Geriatric Assessment for the Prediction of Adverse Outcomes.

OBJECTIVE: To compare the ability of different frailty indexes based on a standardized comprehensive geriatric assessment (FI-CGAs) for predicting adverse outcomes. DESIGN AND SETTING: Prospective cohort study. Geriatric wards of a general hospital. PARTICIPANTS: 307 hospitalized patients ≥ 65 years. MEASUREMENTS: The FI-CGA-10D (potential health deficits in ten functional domains), the FI-CGA-10D+CM (aforementioned potential health deficits and co-morbidity burden) and the FI-CGA-MIHD (multiple, individual potential health deficits, including functional deficits, co-morbid diseases, amongst others) were assessed at baseline during the patients` hospital stay. The FI-CGAs were analyzed as categorical (according to a FI-CGA score < and ≥ 0.25) and continuous variables. Patients were followed up over 6 months. RESULTS: The FI-CGA-10D, FI-CGA-10+CM and the FI-CGA-MIHD predicted 6-month mortality when expressed as categorical (area under the receiver operating characteristic curve (AUC): AUC = 0.611, AUC = 0.637, AUC = 0.616, all p < 0.050, respectively) or continuous variables (AUC = 0.769, AUC = 0.837, AUC = 0.834, all p < 0.001, respectively). AUC comparisons showed that all three FI-CGAs exhibited a comparable ability to predict 6-month mortality when the FI-CGAs were expressed as categorical variables (all p > 0.200) and the FI-CGA-10D+CM and the FI-CGA-MIHD showed a better ability to predict 6-month mortality than the FI-CGA-10D, when the FI-CGAs were expressed as continuous variables (p < 0.001 and p = 0.007, respectively). None of the FI-CGAs predicted any of the other outcomes, i.e., unplanned re-admission to hospital and a fall during follow-up, irrespective of whether the FI-CGAs were expressed as categorical or continuous variables (all p ≥ 0.050). CONCLUSIONS: The more complex FI-CGAs, i.e., the FI-CGA-10D+CM and the FI-CGA-MIHD, revealed better ability to predict 6 month mortality than the more simple FI-CGA, i.e., the FI-CGA-10D.

Analysis of Rockwood et Al's Clinical Frailty Scale and Fried et Al's Frailty Phenotype as Predictors of Mortality and Other Clinical Outcomes in Older Patients Who Were Admitted to a Geriatric Ward.

OBJECTIVES: There are few data regarding the accuracy of short frailty tools as predictors of mortality and other clinical outcomes of older patients admitted to a geriatric ward. We therefore analyzed the accuracy of Rockwood et al's Clinical Frailty Scale and an easy and quick to perform operationalization of Fried et al's frailty phenotype, as predictors of mortality and other clinical outcomes in our cohort of patients. DESIGN: Prospective analysis with a follow-up period of 6 months. SETTING AND PARTICIPANTS: 307 patients who were 65 years of age or older were included in the study. The patients were assessed in terms of the two frailty measures during their stay in a geriatric ward. RESULTS: The Clinical Frailty Scale and the frailty phenotype were both suitable for differentiating between patients who died due to any cause from those who survived during follow-up (primary outcome) (area under the ROC curves (AUC) values 0.867 (95% CI 0.807-0.926), p<0.001 and 0.754 (95% CI 0.688-0.821), p<0.001, respectively). Regarding the secondary outcomes: 1. unplanned admission to hospital and 2. a fall during follow-up, the Clinical Frailty Scale discriminated or tended to discriminate between patients to whom these criteria applied and those to whom they did not (AUC=0.569 (95% CI 0.502-0.636), p=0.046 and AUC=0.574 (95% CI 0.501-0.647), p=0.071, respectively). The frailty phenotype did not show such a differentiation when applied to secondary outcomes (AUC=0.500 (95% CI 0.432-0.568), p=0.994 and AUC=0.518 (95% CI 0.439-0.598), p=0.658, respectively). CONCLUSIONS: Both short frailty instruments are suitable predictors of mortality in older patients who were admitted to a geriatric ward. The Clinical Frailty Scale, but not the frailty phenotype, predicted at least some of the secondary outcomes, i.e., the outcome unplanned admission to hospital during follow-up.

Sustained nuclear localization of p21/WAF-1 upon growth arrest induced by contact inhibition.

We assessed the expression and distribution of p21/Waf-1 in TLM1 melanoma cells that exhibit contact inhibition and require serum for growth. The growth stage of cells stimulated to enter the mitotic cell cycle synchronously and grow to confluence was characterized by distinct, yet consistent levels and patterns of distribution of p21/Waf-1. Significantly, sustained accumulation of p21/Waf-1 in the nuclear compartment was seen only after 4 days in culture when cell-to-cell contacts were established, leading to a diminished rate of cell growth. Overexpression of wild-type waf-1 in melanoma cells reduced growth of subconfluent cells, decreased Cdk4 activity with a concomitant increase in hypophosphorylated Rb, and promoted cell death by apoptosis. The data support the premise that cell-to-cell contacts provide signals that mediate sustained nuclear localization of p21/Waf-1 leading to cell growth arrest; furthermore, an elevation in the activity of this protein can lead to apoptosis.

Growth arrest of melanoma cells is differentially regulated by contact inhibition and serum deprivation.

Both growth-factor deprivation and contact inhibition suppress cell growth; however, the mechanisms by which they inhibit cell proliferation may not be identical. The function of antiproliferative genes and the induction of programmed cell death are among the potential differences between these growth-arrest mechanisms. Specifically, an inverse relation between the expression of cyclin-dependent kinase inhibitors (CDKIs) and the susceptibility to apoptosis has been reported. To test this relation, we examined the features of growth arrest in a canine melanoma cell line, TLM1. Both contact inhibition and serum deprivation halted cell-cycle progression of TLM1 cells in the G1 phase. Prolonged growth arrest of the cells without restimulation resulted in apoptosis; conversely, the cells reentered the cell cycle after release from contact inhibition or on restimulation with serum. Cell-to-cell contact, but not serum deprivation, led to the expression of p53 and p21/Waf-1. The expression of p21/Waf-1 did not prevent apoptosis. Moreover, the ectopic overexpression of CDKIs increased apoptosis. These results support the premise that growth arrest induced by contact inhibition and serum deprivation are mediated through distinct mechanisms. Furthermore, CDKIs are not universal inhibitors of apoptosis, and in some cases, they may initiate or enhance the apoptotic program.

Normal kinematics of carpal bones: a three-dimensional analysis of carpal bone motion relative to the radius.

Normal carpal kinematics were studied in 22 cadaver specimens using a biplanar radiography method. The kinematics of the trapezium, capitate, hamate, scaphoid, lunate, and triquetrum were determined during wrist motion in sagittal and coronal planes. The results were expressed using the concept of the screw displacement axis and converted to describe the magnitude of rotation about and translation along three axes (X-axis: pronation-supination axis, Y-axis: flexion-extension axis, and Z-axis: radial-ulnar deviation axis) commonly used for the wrist. The orientation of these axes is expressed relative to the radius. Within the proximal carpal row, considerable differences of carpal behavior around the Y-axis were observed during sagittal plane motion of the wrist. The scaphoid exhibited the greatest magnitude of rotation, and the lunate the least. The magnitude of rotation of the carpal bones around the X-axis during sagittal plane motion of the wrist was small. The proximal carpal bones exhibited some ulnar deviation in 60 degrees of wrist flexion. During coronal plane motion of the wrist, the magnitude of radial-ulnar deviation of the distal carpal bones was mutually similar and generally of a greater magnitude than that of the proximal carpal bones. The proximal carpal bones experienced some flexion during radial deviation of the wrist and extension during ulnar deviation of the wrist. Translation was generally minimal in all carpal bones throughout wrist motion. This study reports results from the largest cadaver wrist kinematics study completed to date. The accuracy of the current method was improved when compared to previous studies. A sufficient number of specimens to allow statistical comparison was used and minimal interspecimen variability was noted. This study enabled a precise description of quantitative analyses of normal carpal kinematics relative to the radius.

Axial loading induces rotation of the proximal carpal row bones around unique screw-displacement axes.

The changes in carpal bone alignment secondary to the application of an axial compressive load through the major wrist motor tendons while the wrist is kept in neutral position (isometric loading) have been investigated on 13 fresh cadaver specimens using a biplanar radiographic method of kinematic analysis. The scaphoid, lunate and triquetrum rotate an average of 5.1, 4.2, and 3.8 degrees, respectively, around different screw displacement axes, all implying flexion, radial deviation and supination. Based on these findings, a new interpretation of the mechanism by which the wrist remains stable under physiologic loads is provided.