Leg Lymphoedema After Inguinal and Ilio-Inguinal Lymphadenectomy for Melanoma: Results from a Prospective, Randomised Trial.

BACKGROUND: The Evaluation of Groin Lymphadenectomy Extent for Melanoma (EAGLE FM) study sought to address the question of whether to perform inguinal (IL) or ilio-inguinal lymphadenectomy (I-IL) for patients with inguinal nodal metastatic melanoma who have no clinical or imaging evidence of pelvic disease. Primary outcome measure was disease-free survival at 5 years, and secondary endpoints included lymphoedema. METHODS: EAGLE FM was designed to recruit 634 patients but closed with 88 patients randomised because of slow recruitment and changes in melanoma management. Lymphoedema assessments occurred preoperatively and at 6, 12, 18, and 24 months postoperatively. Lymphoedema was defined as Inter-Limb Volume Difference (ILVD) > 10%, Lymphoedema Index (L-Dex®) > 10 or change of L-Dex® > 10 from baseline. RESULTS: Prevalence of leg lymphoedema between the two groups was similar but numerically higher for I-IL at all time points in the first 24 months of follow-up; highest at 6 months (45.9% IL [CI 29.9-62.0%], 54.1% I-IL [CI 38.0-70.1%]) and lowest at 18 months (18.8% IL [CI 5.2-32.3%], 41.4% I-IL [CI 23.5-59.3%]). Median ILVD at 24 months for those affected by lymphoedema was 14.5% (IQR 10.6-18.7%) and L-Dex® was 12.6 (IQR 9.0-17.2). There was not enough statistical evidence to support associations between lymphoedema and extent of surgery, radiotherapy, or wound infection. CONCLUSIONS: Despite a trend for patients who had I-IL to have greater lymphoedema prevalence than IL in the first 24 months after surgery, our study's small sample did not have the statistical evidence to support an overall difference between the surgical groups.

Cell-free culture supernatant of Lactobacillus curvatus Wikim38 inhibits RANKL-induced osteoclast differentiation and ameliorates bone loss in ovariectomized mice.

This study was conducted to investigate the inhibitory effects of the cell-free culture supernatant of Lactobacillus curvatus Wikim 38 (LC38-CS) on RANKL-induced osteoclast differentiation and bone loss in a mice model of ovariectomy-induced post-menopausal osteoporosis. LC38-CS inhibited the RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by LC38-CS treatment of RANKL-treated BMDMs. In addition, LC38-CS decreased the RANKL-induced activation of the TRAF6/NF-κB/MAPKs axis at the early stage and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. PRMT1 and ADMA levels, new biomarkers for osteoclastogenesis, were decreased by LC38-CS treatment. The administration of LC38-CS increased bone volume and bone mineral density in ovariectomized mice in µ-CT analysis. These findings suggest that LC38-CS inhibited RANKL-induced osteoclast differentiation by the downregulation of molecular mechanisms and exerted anti-osteoporotic effects.

Heterogeneous health profiles and healthcare utilization of the middle-aged and elderly with multiple health insurance schemes in China.

OBJECTIVES: China is facing an escalating demand of healthcare services from the middle-aged and elderly. Compared with the traditional view of health on symptoms and diseases, this study aimed to assess the heterogeneous health profiles of middle-aged and elderly Chinese by a person-centered approach. Furthermore, this study examined the effects of health profiles and associated factors on healthcare utilization within the context of China's multiple health insurance schemes. STUDY DESIGN: The study used the 2015 data of China Health and Retirement Longitudinal Study, a nationwide population-based sample of people aged 45 years and older. METHODS: Latent class analysis (LCA) was adopted to identify the heterogeneous health profiles. Two-part models were adopted to assess the effects of associated factors on healthcare utilization. RESULTS: Among 15,250 Chinese aged 45 years and older, six heterogeneous health profiles were identified and labeled as 'Quite Healthy', 'Relatively Healthy', 'Comprehensive Comorbidities', 'Functional Impairment', 'Severe Disability', and 'Relatively Frail'. The Relatively Frail profile was the heaviest healthcare user. The Severe Disability profile took the least use of outpatient services but had relatively high utilization of inpatient services and outpatient expenditure. The Comprehensive Comorbidities profile tended to have the smallest effect on the frequency of visits for both inpatient and outpatient services, but its effect on outpatient expenditure was high. After controlling for health profiles, the significant effects of different health insurance programs on healthcare utilization were discussed. CONCLUSIONS: Introducing health profiles by the person-centered approach of LCA has provided a holistic understanding of complex healthcare demands for middle-aged and elderly Chinese. It is valuable for policy makers to improve healthcare resource allocation targeted for the middle-aged and elderly.

Comparison of two stroke volume variation-based goal-directed fluid therapies for supratentorial brain tumour resection: a randomized controlled trial.

Background: The optimal volume status for neurosurgery has yet to be determined. We compared two fluid protocols based on different stroke volume variation (SVV) cut-offs for goal-directed fluid therapy (GDFT) during supratentorial brain tumour resection. Methods: A randomized, single-blind, open-label trial was conducted. Eighty adult patients undergoing elective supratentorial brain tumour resection were randomly divided into a low SVV and a high SVV group. The SVV cut-offs were used to determine when to initiate colloid infusion. Clinical outcomes and perioperative changes in serum neuronal biomarkers, including S100ß, neurone-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), were compared. Results: Patients in the low SVV group received a higher volume of colloid [869 (SD 404) vs 569 (453) ml; P=0.0025], had a higher urine output [3.4 (2.4) vs 2.5 (1.7) ml kg-1 h-1; P=0.0416] and a higher average cardiac index [3.2 (0.7) vs 2.8 (0.6) litres min-1 m-2; P=0.0204]. Patients in the low SVV group also had a shorter intensive care unit stay [1.4 (0.7) vs 2.6 (3.3) days, P=0.0326], fewer postoperative neurological events (17.5 vs 40%, P=0.0469), attenuated changes in the NSE and GFAP levels, lower intraoperative serum lactate and a higher Barthel index at discharge (all P<0.05). Conclusions: During GDFT for supratentorial brain tumour resection, fluid boluses targeting a lower SVV are more beneficial than a restrictive protocol. Clinical trial registration: NCT02113358.

Intermediate-risk grouping of cervical cancer patients treated with radical hysterectomy: a Korean Gynecologic Oncology Group study.

BACKGROUND: In this study, we sought to identify a criterion for the intermediate-risk grouping of patients with cervical cancer who exhibit any intermediate-risk factor after radical hysterectomy. METHODS: In total, 2158 patients with pathologically proven stage IB-IIA cervical cancer with any intermediate-risk factor after radical hysterectomy were randomly assigned to two groups, a development group and a validation group, at a ratio of 3 : 1 (1620 patients:538 patients). To predict recurrence, multivariate models were developed using the development group. The ability of the models to discriminate between groups was validated using the log-rank test and receiver operating characteristic (ROC) analysis. RESULTS: Four factors (histology, tumour size, deep stromal invasion (DSI), and lymphovascular space involvement (LVSI)) were significantly associated with disease recurrence and included in the models. Among the nine possible combinations of the four variables, models consisting of any two of the four intermediate-risk factors (tumour size ≥3 cm, DSI of the outer third of the cervix, LVSI, and adenocarcinoma or adenosquamous carcinoma histology) demonstrated the best performance for predicting recurrence. CONCLUSION: This study identified a 'four-factor model' in which the presence of any two factors may be useful for predicting recurrence in patients with cervical cancer treated with radical hysterectomy.

Development of microsatellite primers for Jatropha curcas (Euphorbiaceae) and transferability to congeners.

PREMISE OF THE STUDY: Microsatellite primers were developed for Jatropha curcas (Euphorbiaceae), a tree species with large potential for biofuel production, to investigate its natural genetic diversity and mating system to facilitate the establishment of tree improvement and conservation programs. METHODS AND RESULTS: Using a protocol for genomic library enrichment, 104 clones containing 195 repeat motifs were identified. Primer pairs were developed for 40 microsatellite loci and validated in 41 accessions of J. curcas from six provenances. Nine loci were polymorphic revealing from two to eight alleles per locus, and six primers were able to amplify alleles in the congeners J. podagrica, J. pohliana, and J. gossypifolia, but not in other Euphorbiaceae species, such as Hevea brasiliensis, Manihot esculenta, or Ricinus communis. CONCLUSIONS: The primers developed here revealed polymorphic loci that are suitable for genetic diversity and structure, mating system, and gene flow studies in J. curcas, and some congeners.

Does targeted pre-load optimisation by stroke volume variation attenuate a reduction in cardiac output in the prone position.

The prone position can reduce cardiac output by up to 25% due to reduced preload. We hypothesised that preload optimisation targeted to stroke volume variation before turning prone might alleviate this. A supine threshold stroke volume variation of 14% in a preliminary study identified patients whose cardiac outputs would decline when turned prone. In 45 patients, cardiac output declined only in the group whose supine stroke volume variation was high (mean (SD) 5.1 (2.0) to 3.9 (1.9) l.min(-1) ; p < 0.001), but not in patients in whom it was low, or in those in whom stroke volume variation was high, but who received volume preload (p = 0.525 and 0.941, respectively). We conclude that targeted preload optimisation using a supine stroke volume variation value < 14% is effective in preventing falls in cardiac output induced by the prone position.

Nutritional Status and Risks of Cognitive Decline and Incident Neurocognitive Disorders: Singapore Longitudinal Ageing Studies.

BACKGROUND: Studies suggest that nutritional interventions using the whole diet approach such as the Mediterranean diet may delay cognitive decline and dementia onset. However, substantial numbers of older adults are non-adherent to any ideally healthy dietary pattern and are at risk of malnutrition. OBJECTIVE: The present study investigated the relationship between global malnutrition risk and onsets of cognitive decline and neurocognitive disorders (NCD), including mild cognitive impairment (MCI) or dementia in community-dwelling older adults. METHODS: Participants aged ≥ 55 years in the Singapore Longitudinal Ageing Studies (SLAS) were assessed at baseline using the Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA) and followed up 3-5 years subsequently on cognitive decline (MMSE drop ≥ 2) among 3128 dementia-free individuals, and incident neurocognitive disorders (NCD) among 2640 cognitive normal individuals. RESULTS: Individuals at high nutritional risk score (≥ 3) were more likely to develop cognitive decline (OR=1.42, 95%CI=1.01-1.99) and incident MCI-or-dementia (OR=1.64, 95%CI=1.03-2.59), controlling for age, sex, ethnicity, low education, APOE-e4, hearing loss, physical, social, and mental activities, depressive symptoms, smoking, alcohol, central obesity, hypertension, diabetes, low HDL, high triglyceride, cardiac disease, and stroke. Among ENIGMA component indicators, low albumin at baseline was associated with cognitive decline and incident NCD, and 5 or more drugs used, few fruits/vegetables/milk products daily, and low total cholesterol were associated with incident NCD. CONCLUSION: The ENIGMA measure of global malnutrition risk predicts cognitive decline and incident neurocognitive disorders, suggesting the feasibility of identifying vulnerable subpopulations of older adults for correction of malnutrition risk to prevent neurocognitive disorders.

Development, Validation and Field Evaluation of the Singapore Longitudinal Ageing Study (SLAS) Risk Index for Prediction of Mild Cognitive Impairment and Dementia.

BACKGROUND: Mild cognitive impairment (MCI) is a critical pre-dementia target for preventive interventions. There are few brief screening tools based on self-reported personal lifestyle and health-related information for predicting MCI that have been validated for their generalizability and utility in primary care and community settings. OBJECTIVE: To develop and validate a MCI risk prediction index, and evaluate its field application in a pilot community intervention trial project. DESIGN: Two independent population-based cohorts in the Singapore Longitudinal Ageing Study (SLAS). We used SLAS1 as a development cohort to construct the risk assessment instrument, and SLA2 as a validation cohort to verify its generalizability. SETTING: community-based screening and lifestyle intervention Participants: (1) SLAS1 cognitively normal (CN) aged ≥55 years with average 3 years (N=1601); (2) SLAS2 cohort (N=3051) with average 4 years of follow up. (3) 437 participants in a pilot community intervention project. MEASUREMENTS: The risk index indicators included age, female sex, years of schooling, hearing loss, depression, life satisfaction, number of cardio-metabolic risk factors (wide waist circumference, pre-diabetes or diabetes, hypertension, dyslipidemia). Weighted summed scores predicted probabilities of MCI or dementia. A self-administered questionnaire field version of the risk index was deployed in the pilot community project and evaluated using pre-intervention baseline cognitive function of participants. RESULTS: Risk scores were associated with increasing probabilities of progression to MCI-or-dementia in the development cohort (AUC=0.73) and with increased prevalence and incidence of MCI-or-dementia in the validation cohort (AUC=0.74). The field questionnaire risk index identified high risk individuals with strong correlation with RBANS cognitive scores in the community program (p<0.001). CONCLUSIONS: The SLAS risk index is accurate and replicable in predicting MCI, and is applicable in community interventions for dementia prevention.

Disentangling the dynamical origin of P11 nucleon resonances.

We show that two almost degenerate poles near the piDelta threshold and the next higher mass pole in the P11 partial wave of piN scattering evolve from a single bare state through its coupling with piN, etaN, and pipiN reaction channels. This finding provides new information on understanding the dynamical origins of the Roper N{*}(1440) and N{*}(1710) resonances listed by Particle Data Group. Our results for the resonance poles in other piN partial waves are also presented.

Elucidating therapeutic effects on patients with hepatocellular carcinoma and main portal vein thrombosis.

BACKGROUND/AIMS: The survival duration for patients diagnosed with hepatocellular carcinoma (HCC) with main portal vein thrombosis (MPVT) was usually less than 3 months. The aim of this study is to elucidate whether treatment can prolong the survival for such patients. METHODOLOGY: Retrospectively we analyzed the clinical features and outcomes of 63 patients with HCC and MPVT over a 7-year period. Three therapeutic modalities--transcatheter arterial chemotherapy (TAC) with or without radiotherapy (RT), and systemic chemotherapy--were applied. RESULTS: The patients were divided into two groups: 34 (54%) patients were treated, while the remaining 29 (46%) were not. Multivariate analysis revealed that Child-Pugh class, Okuda stage for HCC and the presence of treatment were the principal factors to predict survival. The survival was significantly longer in treated patients than those untreated both in the Child-Pugh class A or B patients. Significantly longer survival is evident in patients treated by TAC combing RT compared to those underwent TAC alone, systemic chemotherapy or no treatment. CONCLUSIONS: The survival of Child-Pugh class A or B patients can be extended by the use of an appropriate therapeutic modality. TAC combined with RT did the best benefit to prolong survival in such patients.

The effect of vertebral material description during vertebroplasty.

Vertebroplasty has attracted much attention as a medical treatment for the collapse of the spine by strengthening the vertebral body, correcting deformities, and relieving pain in patients through the injection of bone cement. The finite element method has become popular for analysing vertebroplasty. The numerical modelling of vertebrae under loading, as in many other cases of representing a composite bone with anatomically scattered properties through a simplified material model, entails difficulties in material assignment for analysis. The aim of this study is to compare and contrast material-assignment methods in the course of modelling through a tetrahedral meshing algorithm. In particular, the study seeks to contrast the element-wise material model with a uniform material assignment for trabecular bone and the bone-poly(methyl methacrylate) (PMMA) composite. The geometries of the vertebral body are constructed from computed tomography image data, which are obtained through scanning at intervals of 1 mm. The finite element models are constructed through a tetrahedral meshing algorithm. Various types of material assignment, which encompass the case of normal persons as well as the case of patients following vertebroplastic surgery, are analysed. The results clearly show that the oversimplification of the trabecular bone and the bone-PMMA composite body may lead to significant deviations in the assessment of the effectiveness of vertebroplastic surgery.

Helical rim advancement - A technique to avoid keloid recurrence.

INTRODUCTION: Helical rim keloids occur commonly following ear piercings, trauma and previous surgeries and can be disfiguring. Many techniques have been developed to treated these disfiguring lesions with varying successes, however, individuals prone to developing keloids inadvertently recur despite best efforts. OBJECTIVE: To determine whether helical rim advancement flap reconstruction following helical rim keloid excision can reduce recurrences. DESIGN: Case series followed up to 2 years. SETTING: Single Centre Tertiary Hospital Facial Plastics Service. PARTICIPANTS: All patients who consented to helical rim advancement reconstruction after keloid excision. RESULTS: The authors report a series of 7 patients with helical rim keloids ranging from 1.2 cm to 5 cm in widest diameter treated with keloid excision and reconstruction with helical rim advancement flap technique. There were no recurrences within a mean of about 19 months post-operatively. Most patients report satisfaction with the cosmetic end-result. DISCUSSION: From the authors' experience, helical rim advancement reconstruction following excision of keloids about 2.5 cm in widest diameter is an excellent tension-free option to avoid recurrence of helical rim keloids. Wound tension is a key risk factor for keloid formation. We hypothesise that the reason why there was no recurrence is because in helical rim advancement flap reconstruction, the underlying helical rim takes all the tension of closure off the dermis, resulting in tension-free skin closure. CONCLUSION: Helical rim advancement flap reconstruction is a viable technique to avoid recurrence and minimise cosmetic deformities of the pinna for selected helical rim keloids.

Case report of a type III endoleak presenting only decades after endovascular aortic repair.

INTRODUCTION: Type III endoleaks are a rare but potentially life-threatening complication post endovascular aortic aneurysm repair (EVAR). CASE REPORT: A 91-year-old Chinese female, presented to our accident and emergency department for severe back and abdominal pain. She had previously undergone an EVAR procedure twenty years ago for a 6.5 cm diameter infra-renal abdominal aortic aneurysm. A CT aortogram revealed a type III endoleak, with the contralateral limb found to be disconnected from the main graft body. She was successfully treated by relining the graft using an endovascular technique. DISCUSSION: The case highlights the need for life-long stent-graft surveillance. We discuss early generation stent-grafts, type III endoleak treatment options and the current long-term data for late EVAR-related complications. CONCLUSION: For patients who had undergone EVAR, type III endoleaks can present only decades later and pose a significant risk of aneurysmal rupture.

Hereditary neuropathy with liability to pressure palsies: description of seven patients without known family history.

OBJECTIVES: Hereditary neuropathy with liability to pressure palsies (HNPP) is an inherited disorder resulting in a polyneuropathy with particular involvement at sites of entrapment, and is often underdiagnosed or misdiagnosed. We report findings on seven patients referred for evaluation of focal mononeuropathies or polyneuropathies of undetermined etiology, in whom we established a diagnosis of HNPP. MATERIALS AND METHODS: We retrospectively reviewed clinical, electrophysiological and laboratory data for patients diagnosed with HNPP over a 4-year period at our institution. RESULTS: All patients had transient or recurrent neurological symptoms, some with residual deficits. No patients had a family history of any neuropathy. Electrodiagnostic studies revealed abnormal conduction findings at symptomatic and asymptomatic sites. Testing for the Peripheral Myelin Protein (PMP22) deletion was positive in all patients. CONCLUSIONS: A high index of clinical suspicion and thorough electrodiagnostic evaluation can lead to correct diagnosis of HNPP, despite the absence of a positive family history.

Traction suture modification to tongue-in-groove caudal septoplasty.

Caudal septal deviation leads to unfavorable esthetic as well as functional effects on the nasal airway. A modification to the tongue-in-groove (TIG) technique to correct these caudal septal deformities is described. With placement of a temporary suspension suture to the caudal septum, manual traction is applied, assuring that the caudal septum remains in the midline position while it is being secured with multiple through-and-through, trans-columellar and trans-septal sutures. From 2003 to 2016, 148 patients underwent endonasal septoplasty using this modified technique, with excellent functional and cosmetic outcomes and a revision rate of 1.4%. This modified TIG technique replaces the periosteal suture that secures the caudal septum to the midline nasal crest in the original TIG technique. This simplifies the procedure and minimizes the risk of securing the caudal septum off-midline when used in endonasal septoplasty.

Differential regulation of protein kinase C and (Na,K)-adenosine triphosphatase activities by elevated glucose levels in retinal capillary endothelial cells.

Elevated cellular sorbitol levels resulting from conversion of increased glucose by aldose reductase might deplete cellular myoinositol content, which could then lower inositol phosphates (InsPs) and diacylglycerol levels, key regulators of protein kinase C (PKC). Secondary to altered PKC activity, other cellular enzymes such as (Na,K)-ATPase could be affected. To test this hypothesis we examined the association between PKC activity, (Na,K)-ATPase activity, and sorbitol, myoinositol, and InsP levels in cultured bovine retinal capillary endothelial cells, a cell type prominently involved in diabetic retinopathy. Elevating glucose concentration in culture media from 100 to 400 mg/dl led to a 100% increase in sorbitol levels, which could be inhibited completely by sorbinil, an aldose reductase inhibitor. In contrast, no changes were observed in myoinositol or InsP levels. Subfractionated PKC activities showed a 100% increase in the membranous pool with a parallel decrease in the cytosolic fraction. Adding sorbinil did not affect PKC activity, whereas the PKC agonist, phorbol myristate acetate (PMA), stimulated translocation of PKC. Ouabain-inhibitable (Na,K)-ATPase activity was decreased 70% by elevated glucose levels. This decrease could be prevented by adding either PMA or sorbinil. Thus, in retinal capillary endothelial cells elevated glucose concentration can affect PKC and (Na,K)-ATPase activities, probably via different mechanisms.