Frailty predicts mortality in all emergency surgical admissions regardless of age. An observational study.

BACKGROUND: frail patients in any age group are more likely to die than those that are not frail. We aimed to evaluate the impact of frailty on clinical mortality, readmission rate and length of stay for emergency surgical patients of all ages. METHODS: a multi-centre prospective cohort study was conducted on adult admissions to acute surgical units. Every patient presenting as a surgical emergency to secondary care, regardless of whether they ultimately underwent a surgical procedure was included. The study was carried out during 2015 and 2016.Frailty was defined using the 7-point Clinical Frailty Scale. The primary outcome was mortality at Day 90. Secondary outcomes included: mortality at Day 30, length of stay and readmission within a Day 30 period. RESULTS: the cohort included 2,279 patients (median age 54 years [IQR 36-72]; 56% female). Frailty was documented in patients of all ages: 1% in the under 40's to 45% of those aged 80+. We found that each incremental step of worsening frailty was associated with an 80% increase in mortality at Day 90 (OR 1.80, 95% CI: 1.61-2.01) supporting a linear dose-response relationship. In addition, the most frail patients were increasingly likely to stay in hospital longer, be readmitted within 30 days, and die within 30 days. CONCLUSIONS: worsening frailty at any age is associated with significantly poorer patient outcomes, including mortality in unselected acute surgical admissions. Assessment of frailty should be integrated into emergency surgical practice to allow prognostication and implementation of strategies to improve outcomes.

Rare T-Cell Subtypes.

There are a number of rare T-cell lymphoma subtypes that may be encountered in clinical practice. In recent years, improved immunohistochemical techniques and molecular tumor profiling have permitted refinement of some of the diagnostic categories in this group, as well as the recognition of distinct conditions not previously well elucidated. In this chapter, we cover the diagnostic and clinical features of some of the more common of these conditions, including subcutaneous panniculitis-like T-cell lymphoma, cutaneous gamma-delta T-cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, CD4-positive small/medium T-cell lymphoproliferative disorder, and acral CD8-positive T-cell lymphoma. Given the rarity of these conditions, optimal treatments approaches are not always well established, not least as data from large-scale clinical trials are lacking. In this chapter, we aim to provide a summation of current thinking around best treatment, as well as highlighting some controversies in the management of these diagnoses.

Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma.

Background: As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance. Patients and methods: From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were carried out of imaging outcomes. Results: One hundred and seventy patients (stage 3A: 34; 3B: 93; 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of individual scans were 56%-83%. Negative scans had predictive values of 89%-96% for true non-recurrence [negative predictive values (NPV)] until the next scan. A negative PET at 18 months had NPVs of 80%-84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median). Conclusions: Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium.

BACKGROUND: Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. PATIENTS AND METHODS: This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). RESULTS: Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. CONCLUSION: This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

Modelling the role of groundwater hydro-refugia in East African hominin evolution and dispersal.

Water is a fundamental resource, yet its spatiotemporal availability in East Africa is poorly understood. This is the area where most hominin first occurrences are located, and consequently the potential role of water in hominin evolution and dispersal remains unresolved. Here, we show that hundreds of springs currently distributed across East Africa could function as persistent groundwater hydro-refugia through orbital-scale climate cycles. Groundwater buffers climate variability according to spatially variable groundwater response times determined by geology and topography. Using an agent-based model, grounded on the present day landscape, we show that groundwater availability would have been critical to supporting isolated networks of hydro-refugia during dry periods when potable surface water was scarce. This may have facilitated unexpected variations in isolation and dispersal of hominin populations in the past. Our results therefore provide a new environmental framework in which to understand how patterns of taxonomic diversity in hominins may have developed.

High HIV incidence in men who have sex with men attending for postexposure prophylaxis: a service evaluation.

BACKGROUND/AIMS: There are limited outcome data for men who have sex with men (MSM) who have received HIV postexposure prophylaxis (PEP). The objective of this service evaluation was to determine HIV incidence and repeat PEP use among MSM PEP recipients in London, UK. METHODS: Retrospective electronic case-note review of all MSM who were prescribed PEP between January and April 2013 at a central London sexual health service. RESULTS: 530 MSM received PEP between 1 January and 30 June 2013. Of these, 449 had more than 30 days subsequent follow-up at our service. Median age was 31 years. PEP indication was unprotected anal intercourse, 98% (receptive 88% and insertive 10%) and other, 2%. Up to 1 November 2015, total follow-up was 756 person-years. 183 users received repeat PEP. The total number of repeat PEP courses was 442. 57 MSM newly acquired HIV: the HIV incidence was 7.6 per 100 person-years. CONCLUSIONS: PEP was associated with a high risk of subsequent HIV seroconversion in this cohort; this group may be appropriate candidates for pre-exposure prophylaxis.

Preoperative endoscopy may reduce the need for revisional surgery for gastro-oesophageal reflux disease following laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy is a safe and effective bariatric operation, but postoperative reflux symptoms can sometimes necessitate revisional surgery. Roux-en-Y gastric bypass is the preferred operation in morbidly obese patients with gastro-oesophageal reflux disease. In 2011, we introduced preoperative endoscopy to assess for hiatus hernia or evidence of oesophagitis in conjunction with an assessment of gastro-oesophageal reflux symptoms for all patients undergoing bariatric surgery with a view to avoid sleeve gastrectomy for these patients. A prospectively maintained database was used to identify patients who underwent sleeve gastrectomy before and after we changed the unit policy. The need for revisional surgery in patients with troublesome gastro-oesophageal reflux disease was examined. Prior to 2011, 130 patients underwent sleeve gastrectomy, and 11 (8.5%) of them required conversion to Roux-en-Y gastric bypass for symptomatic reflux disease. Following the policy change, 284 patients underwent sleeve gastrectomy, and to date, only five (1.8%) have required revisional surgery (p = 0.001). Baseline demographics were comparable between the groups, and average follow-up period was 47 and 33 months, respectively, for each group. Preoperative endoscopy and a detailed clinical history regarding gastro-oesophageal reflux symptoms may improve patient selection for sleeve gastrectomy. Avoiding sleeve gastrectomy in patients with reflux disease and/or hiatus hernia may reduce the incidence of revisional surgery.

Localized melanoma in older patients, the impact of increasing age and comorbid medical conditions.

BACKGROUND: Elderly patients experience a different spectrum of disease and poorer outcomes than younger patients. This study investigated the impact of age and medical comorbidities on the management and outcome of patients ≥65 years. METHODS: A retrospective review of all patients ≥65 years (481 patients with 525 primary melanomas) presenting with AJCC clinical stage I-II melanoma to an Australian cancer centre between 2000 and 2008. RESULT: The median age was 74 years (65-94) with a male predominance (313 males, 65.0%) and median tumour thickness of 1.90 mm (IQR = 0.40-2.90, T1 = 33%, T2 = 20%, T3 = 24%, T4 = 23%). Inadequate surgical margins of excision (<10 mm) were common in older patients independent of site, thickness and ulceration (OR = 1.04, 95%CI = 1.00-1.07, p = 0.038). Inadequate excision margins were strongly associated with time to local recurrence, independent of age, thickness, ulceration and mitotic rate (HR = 3.00, 95%CI = 1.49-6.03, p = 0.0021), but not time to progression (p = 0.10) or disease specific survival (DSS, p = 0.27). Overall survival (OS) was strongly related to increasing age (HR = 1.04, 95%CI = 1.01-1.07, p = 0.015) and comorbid medical conditions (HR = 1.26, 95%CI = 1.12-1.42, p < 0.001), as assessed by the Charlson comorbidity index (CCI). DSS was significantly related to CCI (HR = 1.20, 95%CI = 1.01-1.42, p = 0.041) and not age (p = 0.46), when adjusting for thickness, ulceration and mitotic rate on multivariate analysis. CONCLUSION: Older patients present with poor prognosis melanomas yet are less likely to receive adequate surgical excision margins resulting in higher rates of local recurrence. In melanoma patients ≥65 years, the increasing number of medical comorbidities explains much of the age related variations in OS and DSS and should be considered when planning treatment.

Neuropsychological and social cognitive function in young people at genetic risk of bipolar disorder.

BACKGROUND: Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives. METHOD: Neurocognitive and social cognitive ability was examined in 99 young people (age range 16-30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD. RESULTS: Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs. CONCLUSIONS: Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.

Randomised trial of cervical cerclage, with and without occlusion, for the prevention of preterm birth in women suspected for cervical insufficiency.

OBJECTIVE: To evaluate the effect of cerclage, with and without cervical occlusion. DESIGN: Multicentre, stratified, randomised controlled trial. SETTING: Hospital-based multicentre study with 18 tertiary centres from nine countries. POPULATION: Women with a history of cervical insufficiency (prophylactic trial) and women with a short cervix (therapeutic trial) were recruited from August 2006 to August 2011. METHODS: A centralised telephone randomisation service with a computer system was used to randomise women to cervical cerclage with or without cervical occlusion. Only the analyst performing the interim analyses was blinded. MAIN OUTCOME MEASURES: The take-home baby rate (number of infants discharged alive from the hospital), gestational age at delivery, and the number of days in the neonatal intensive care unit (NICU). RESULTS: Women (n = 309) were stratified into the prophylactic trial (n = 213) or the therapeutic trial (n = 96). The trial stopped early due to slow recruitment and an interim analysis showing no benefit of occlusion. Final analysis comprised 197 women in the prophylactic trial and 87 women in the therapeutic trial. No added effect of cervical occlusion was found in terms of the take-home baby rate in the prophylactic trial (92 versus 90%, RR 1.03, 95% CI 0.94-1.12) or in the therapeutic trial (81 versus 85%, RR 0.96, 95% CI 0.79-1.16). No effect of cervical occlusion was found in terms of gestational age at delivery and number of days the neonate spent in the NICU. Cervical occlusion was associated with no harm. CONCLUSIONS: Cervical occlusion with cerclage had no significant additional effect.

The effect of improving the thermal quality of cold housing on blood pressure and general health: a research note.

OBJECTIVE: To examine the effect of improving the thermal quality of housing on blood pressure (BP) and general health. DESIGN: A before and after study comparing the changes of the intervention with controls. SETTING: Four blocks of flats in the Easthall area of Easterhouse in Glasgow. PARTICIPANTS: Residents of the four blocks who agreed to participate. INTERVENTION: Two blocks of flats were upgraded from being cold, damp and mouldy to being comfortably warm, dry and mould free throughout. MAIN OUTCOME MEASURES: Changes in BP, general health and financial status. RESULTS: In the intervention subjects, systolic and diastolic blood pressures fell very significantly (p<0.000). There was also an improvement in general health as reported subjectively, and as indicated by a reduction in the use of medication and in hospital admissions. In addition, there was a markedly reduced expenditure on heating costs and other previous expenses. There were no changes in the control subjects in any of these measures. CONCLUSION: Improving the thermal quality of housing to eliminate damp and mould and produce a comfortable temperature throughout the house has a major impact on the health of the residents. There are also financial benefits for the residents, and indirectly for the NHS.

Cervical occlusion in women with cervical insufficiency: protocol for a randomised, controlled trial with cerclage, with and without cervical occlusion.

OBJECTIVE: To evaluate the effect of double cerclage compared with a single cerclage. DESIGN: Randomised, controlled multicentre trial. SETTING: Ten different countries are participating with both secondary and tertiary centres. The countries participating are Denmark, Sweden, Germany, United Kingdom, Spain, South Africa, Australia and India. This gives both a broad spectrum of diversity global and local. We expect a total of 242 women enrolled per year. POPULATION: Prophylactic study: 1. History of cervical incompetence/insufficiency. (Delivery 15 to <36 weeks.) 2. Congenital short cervix (secondary to maternal administration of diethyl stilbestrol) or traumatic/surgical damage rendering the vaginal approach difficult (e.g. conisation). 3. Cervical suture applied in previous pregnancy, successful outcome. 4. Previous failed cerclage. Therapeutic study: 5. Secondary cerclage: Short cervix, without the membranes being exposed to the vagina. 6. Tertiary cerclage: Short cervix, membranes exposed to the vagina. Observational study: Eligible women who refuse to be randomised will participate in an observational study. 7. Repeat/requested cervical occlusion. METHODS: The women will be randomised between a single (vaginal or abdominal) and a double cerclage. The cervical cerclage (McDonald or Shirodkar) as well as the abdominal suture will be performed with the same material and technique normally used by the participating department. Those randomised to the double cerclage will have their external os closed with a continuous nylon 2-0/3-0 suture, in addition to the standard single cerclage. Local guidelines concerning antibiotics, Heparin, bed rest, tocolytics etc. are followed and recorded in the follow-up form. MAIN OUTCOME MEASURES: Primary endpoint is take home baby rate. The secondary endpoints are gestational age at delivery, incidence of preterm birth (<34+0 days) and number of days in neonatal unit.

Rituximab in the adjuvant treatment of pemphigus vulgaris: a prospective open-label pilot study in five patients.

BACKGROUND: Rituximab is a monoclonal antibody directed against the CD20 antigen expressed on B lymphocytes. There are reports of its efficacy in the treatment of autoimmune diseases, including pemphigus. OBJECTIVES: Prospectively to evaluate the efficacy of rituximab as adjuvant treatment for pemphigus vulgaris (PV). METHODS: Patients with PV were treated with intravenous rituximab (375 mg m(-2)) weekly for 4 weeks in this prospective open-label pilot study. Other concurrent immunosuppression was continued. RESULTS: Of five patients, one achieved complete remission and was able to cease all medication, while two achieved clearance of clinical lesions but continued on systemic therapy. Two patients had progressive disease. Time to response was 2-8 months, with a 13- to 18-month response duration. Response was associated with reduction in serum antiepithelial antibodies. Two patients had significant infectious complications (one developed community-acquired pneumonia associated with delayed-onset neutropenia and the other developed cytomegalovirus infection). CONCLUSIONS: Rituximab has shown efficacy in the treatment of PV. Patients on multiple immunosuppressives should be closely monitored for infectious complications.

Long-term clearance of patch-stage mycosis fungoides with the 308-nm laser.

In order to investigate the effectiveness of the 308-nm xenon chloride laser in the treatment of patch-stage mycosis fungoides that is refractory to topical steroids, we conducted a prospective, histologically controlled, open-label pilot study. Eight patients with stage 1A or 1B cutaneous T-cell lymphoma that was unresponsive to application of potent topical steroids received 20 treatments with the laser over 10 weeks and were then followed up for a minimum of 30 months. Three patients had a complete clinical and histological response and remained free of disease after 30 months A further three patients had complete clinical and histological clearance of disease, but experienced relapse within the 30 months follow-up period. One patient withdrew from the study and one had a partial response. Further research to establish the role of the 308-nm laser in the treatment of MF appears justified.

Lack of apoptosis of Sézary cells in the circulation following oral bexarotene therapy.

BACKGROUND: Apoptosis of malignant cells has been suggested as an important mechanism of the action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL). OBJECTIVES: Our purpose was to examine the in vivo and in vitro responses of patients with Sézary syndrome treated with oral bexarotene and assess them for apoptosis of the Sézary cells. METHODS: Six patients with CTCL with circulating Sézary cells, participating in a clinical trial of oral bexarotene (300 mg m(-2) daily) were included in the study. Peripheral blood from the patients was analysed for in vivo and in vitro apoptosis. RESULTS: None of the six patients demonstrated in vivo apoptosis. In vitro apoptosis of Sézary cells was demonstrated in one patient following exogenous bexarotene. CONCLUSIONS: Apoptosis is not detectable in the circulation of patients with Sézary syndrome treated with bexarotene.