Nutritional care pathways in cancer patients with malignant bowel obstruction: A retrospective multi-centre study.

INTRODUCTION: Variation in access to parenteral nutrition (PN) in patients with intestinal failure secondary to malignant bowel obstruction (MBO) exists due to differing practice, beliefs and resource access. We aimed to examine differences in nutritional care pathways and outcomes, by referral to nutrition team for PN in patients with MBO. METHODS: This is a retrospective cohort study of MBO adults admitted to eight UK hospitals within a year and 1 year follow-up. Demographic, nutritional and medical data were analysed by comparing patients referred (R) or not referred (NR) for PN. Differences between groups were tested by Kruskal-Wallis, Chi-Squared tests and multi-level regression and survival using Cox regression. RESULTS: 232 patients with 347 MBO admissions [median 66yr, (IQR: 55-74yrs), 67 % female], 79/232 patients were referred for PN (R group). Underlying primary malignancies of gynaecological and gastrointestinal origin predominated (71 %) and 78 % with metastases. Those in the NR group were found to be older, weigh more on admission, and more likely to be treated conservatively compared to those in the R group. For 123 (35 %) admissions, patients were referred to a nutrition team, and for 204 (59 %) admissions, patients were reviewed by a dietician. Multi-disciplinary team discussion and dietetic contact were more likely to occur in the R group-123/347 admissions (R vs NR group: 27 % vs. 7 %, P = 0.001; 95 % vs 39 %, P < 0.0001). Median admission weight loss was 8 % (IQR: 0 to 14). 43/123 R group admissions received inpatient PN only, with 32 patients discharged or already established on home parenteral nutrition. Overall survival was 150 days (126-232) with no difference between R/NR groups. CONCLUSION: In this multi-centre study evaluating nutritional care management of patients with malignant bowel obstruction, only 1 in 3 admissions resulted in a referral to the nutrition team for PN, and just over half were reviewed by a dietician. Further prospective research is required to evaluate possible consequences of these differential care pathways on clinical outcomes and quality of life.

COVID-19 community assessment hubs in Ireland: A study of staff and patient perceptions of their value.

BACKGROUND: Critical care bed capacity per capita in Ireland is among the lowest in Europe. The COVID-19 pandemic has put additional strain on an over-stretched healthcare system. COVID-19 community assessment hubs (CAHs) were established to prevent unnecessary admission to acute hospitals and to reduce infection spread. OBJECTIVE: The aim of this study was to assess the effectiveness and acceptability of CAHs and identify how the service might be improved or adapted for possible future use. DESIGN: This was a mixed methods study, incorporating co-design with clinical stakeholders. Data collection was via an online survey and semistructured telephone interviews with staff and patients conducted between January and May 2021. SETTING AND PARTICIPANTS: Thirty-one patients completed the survey and nine were interviewed. Twenty interviews were conducted with staff. RESULTS: The findings suggest that the CAH model was successful in providing a dedicated pathway for assessing patients with COVID-19 symptoms, whilst mitigating the risk of infection. Patients were particularly positive about the timely, comprehensive and holistic care they received, as well as the accessibility of the clinics and the friendly attitudes of the staff. Staff welcomed the training and clinical protocols which contributed to their feelings of safety and competency in delivering care to this cohort of patients. They also highlighted the benefits of working in a multidisciplinary environment. Both staff and patients felt that the hubs could be repurposed for alternative use, including the treatment of chronic diseases. DISCUSSION: This study describes staff and patients' experiences of these hubs. An unexpected outcome of this study is its demonstration of the true value of effective multidisciplinary working, not only for the staff who were deployed to this service but also for the patients in receipt of care in these hubs. CONCLUSION: This multidisciplinary patient-centred service may provide a useful model for the delivery of other services currently delivered in hospital settings. PATIENT OR PUBLIC CONTRIBUTION: An earlier phase of this study involved interviews with COVID-19-positive patients on a remote monitoring programme. The data informed this phase. Several of the authors had worked in the CAHs and provided valuable input into the design of the staff and patient interviews.

Adaptation to HLA-associated immune pressure over the course of HIV infection and in circulating HIV-1 strains.

Adaptation to human leukocyte antigen (HLA)-associated immune pressure represents a major driver of human immunodeficiency virus (HIV) evolution at both the individual and population level. To date, there has been limited exploration of the impact of the initial cellular immune response in driving viral adaptation, the dynamics of these changes during infection and their effect on circulating transmitting viruses at the population level. Capturing detailed virological and immunological data from acute and early HIV infection is challenging as this commonly precedes the diagnosis of HIV infection, potentially by many years. In addition, rapid initiation of antiretroviral treatment following a diagnosis is the standard of care, and central to global efforts towards HIV elimination. Yet, acute untreated infection is the critical period in which the diversity of proviral reservoirs is first established within individuals, and associated with greater risk of onward transmissions in a population. Characterizing the viral adaptations evident in the earliest phases of infection, coinciding with the initial cellular immune responses is therefore relevant to understanding which changes are of greatest impact to HIV evolution at the population level. In this study, we utilized three separate cohorts to examine the initial CD8+ T cell immune response to HIV (cross-sectional acute infection cohort), track HIV evolution in response to CD8+ T cell-mediated immunity over time (longitudinal chronic infection cohort) and translate the impact of HLA-driven HIV evolution to the population level (cross-sectional HIV sequence data spanning 30 years). Using next generation viral sequencing and enzyme-linked immunospot interferon-gamma recall responses to peptides representing HLA class I-specific HIV T cell targets, we observed that CD8+ T cell responses can select viral adaptations prior to full antibody seroconversion. Using the longitudinal cohort, we uncover that viral adaptations have the propensity to be retained over time in a non-selective immune environment, which reflects the increasing proportion of pre-adapted HIV strains within the Western Australian population over an approximate 30-year period.

Online sale of small turtles circumvents public health regulations in the United States.

In the United States (U.S.), pet turtles have been associated with outbreaks of salmonellosis, a serious and sometimes-fatal intestinal illness caused by Salmonella bacteria, with nearly 300,000 people being infected in some years. Children are particularly susceptible because of their propensity to put items, including small turtles, in their mouths. In 1975, a U.S. federal regulation prohibited the sale of turtles <4 inches (101.6 mm) in size, except for the purposes of export, scientific, or educational purposes. This regulation was established to reduce the incidence of salmonellosis, particularly in small children. Previous research has not evaluated the availability of turtles <4 inches in size on websites selling wildlife. We monitored 16 websites in 2021 and quantified listings of small turtles. We determined whether information on Salmonella, the 1975 federal regulation, or related state regulations were provided on the websites and determined legality of sales of small turtles by state regulations. We found that all 16 websites openly advertised and sold turtles <4 inches in size, but only half of these websites provided information about Salmonella and/or the federal regulation. These websites required buyers to confirm that they were not purchasing a turtle as a pet, thereby putting the onus on the consumer to adhere to the regulation. We documented 515 listings of turtles <4 inches in size, including 47 species and one hybrid. Our study has demonstrated that internet sales of small turtles currently represent part of the thriving online pet trade in the U.S. Enforcement of the federal regulation faces jurisdictional challenges in most states. Therefore, we recommend continued public education campaigns by public health agencies in the U.S. to help reduce the risk that pet turtle ownership presents.

Oral, enteral and parenteral nutritional therapies in scleroderma: A systematic review.

BACKGROUND & AIMS: Scleroderma is a multi-system disease that causes hardening of connective tissue. The gastrointestinal (GI) tract is affected in 90% of patients, which may cause nutritional decline. Due to the rarity of the disease, current nutritional guidelines in scleroderma are extrapolated from evidence in other chronic diseases. This systematic review examines the effects of oral nutrition supplements (ONS), enteral nutrition (EN) and parenteral nutrition (PN) on both clinical and nutritional outcomes of scleroderma patients. METHOD: Three separate systematic searches for scleroderma and ONS, EN, and PN were performed. The searches were conducted using EMBASE, PubMed and Web of Science databases. RESULTS: A total of 9 studies (ONS: 2, EN: 1 and PN: 6) met the inclusion and exclusion criteria and were included in the review. All patients had scleroderma and were malnourished or at risk of malnutrition [weighted average age: 53 years, Body Mass Index (BMI): 19 kg/m2]. Artificial nutrition support was shown to be an effective therapy for preventing nutritional decline and reversing malnutrition but had no impact on disease progression. Mean BMI increased with home parenteral nutrition (HPN) and EN, from 15 kg/m2 to 21.0 kg/m2. Weight was maintained with ONS, and sarcopenia decreased. Only HPN positively impacted quality of life and GI symptoms, with complication rates similar to patients with other indications. CONCLUSION: Scleroderma patients should be routinely screened for malnutrition. Malnutrition is treated in a stepwise manner, starting with ONS, then EN and finally PN, based on GI sufficiency and tolerance of the patient. HPN is an effective therapy for patients with advanced disease and intestinal failure. However, larger, long-term, prospective studies for each nutritional therapy are required to make firm conclusions.

A mixed methods protocol to evaluate the effectiveness and acceptability of COVID-19 Community Assessment Hubs.

Background: Ireland's health system has been under significant strain due to staff shortages and inadequate capacity. Critical care bed capacity per capita in Ireland is among the lowest in Europe, thus, the coronavirus disease 2019 (COVID-19) pandemic has put additional strain on an over-stretched system. COVID-19 Community Assessment Hubs (CAHs) were established to mitigate unnecessary admission to acute hospitals, and reduce infection spread by supporting COVID-19 positive or suspected positive patients to isolate at home, or in isolation facilities. There is some evidence that similar assessment centres may be a successful triage strategy to reduce burden on hospital and acute care. Aim : The aim of this study is to evaluate the impact of COVID-19 Community Assessment Hubs on service delivery in one region in Ireland. Methods: A mixed-methods approach will be used, incorporating co-design to engage stakeholders and ensure informed data capture and analysis. Online surveys will assess CAH patients' experiences of access to and quality of care. Clinical patient data from CAHs will be collected and analysed using multinomial logistic regression to check for association with patient demographics and COVID-19 symptoms, and CAH early warning scores and outcomes (Transfer to Emergency Department, Transfer to isolation unit, Sent home with care plan). Semi-structured interviews will be conducted with: patients to elicit an in-depth understanding of experiences and acceptability of attending CAHs; and staff to understand challenges, benefits, and effectiveness of CAHs. Interview data will be analysed using a thematic analysis approach. Discussion: This study will provide valuable insights from both patient and staff perspectives on the operation of CAHs. We will evaluate the effectiveness and acceptability of CAHs and propose areas for improvement of the service. This will contribute to international literature on the use of community assessment centres during infectious disease pandemics.

Clinical and Nutritional Care Pathways of Patients with Malignant Bowel Obstruction: A Retrospective Analysis in a Tertiary UK Center.

We describe a retrospective cohort study of patients with malignant bowel obstruction to examine their nutritional care pathways between 1.1.16 and 31.12.16 with readmissions until 31.12.17. Data were analyzed by comparing patients who were referred (R) and not referred (NR) for PN. We identified 72 patients with 117 MBO admissions (mean ± SD age:63.1 ± 13.1yrs, 79% female). 24/72 patients were in R group. Predominant primary malignancies were gynaecological and lower-gastrointestinal cancers (76%). 83% patients had metastases (61% sub-diaphragmatically). All patients were at high-risk of malnutrition and baseline mean weight loss was 7%. Discussion of PN at multidisciplinary team meeting (MDT) (22% vs.5%, P = 0.02) and dietetic contact (94% vs. 41%, P < 0.0001) were more likely to occur in the R group. In 13/69 MBO admissions in NR group, reasons for non-referral were unclear. Median baseline and follow-up weight was similar (55-55.8 kg). Overall survival was 4.7 (1.4-15.2)months, with no differences by referral groups. We compared a sub-sample of patients who 'may have' required PN (n = 10) vs. those discharged on home PN (n = 10) and found greater survival in the HPN group (323vs.91 day, P < 0.01). Our findings highlight disparity in care pathways suggesting that nutritional care should be integrated into clinical management discussion(s) at MDT to ensure equal access to nutritional services.

A Surviving Case of Acanthamoeba Granulomatous Amebic Encephalitis in a Hematopoietic Stem Cell Transplant Recipient.

BACKGROUND Acanthamoeba are free-living amoebae with potential to infect immunocompromised hosts. The mortality rate of granulomatous amebic encephalitis (GAE) due to Acanthamoeba exceeds 90% and there are currently no reports of survival of this infection in recipients of hematopoietic stem cell transplant. CASE REPORT We report herein the case of a 32-year-old man presenting to our service with abrupt neurological deterioration and seizures 5 months after allogeneic stem cell transplantation for Hodgkin lymphoma. Clinical and imaging findings were non-specific at presentation. Multiple circumscribed, heterogenous, mass-like lesions were identified on MRI. Brain biopsy was performed and revealed multiple cysts and trophozoites suggesting a diagnosis of granulomatous amebic encephalitis. PCR testing confirmed Acanthamoeba. Treatment with miltefosine, metronidazole, azithromycin, fluconazole, pentamidine isethionate, and co-trimoxazole was instituted and the patient survived and shows continued improvement with intensive rehabilitation. CONCLUSIONS We report the first successful outcome in this setting. The diagnosis would have been missed on cerebrospinal fluid analysis alone, but was rapidly made by histological analysis of brain biopsy. This diagnostically challenging infection is likely under-recognized. Early brain biopsy and commencement of a prolonged miltefosine-containing anti-ameba regimen can be curative.

Refeeding syndrome in adults receiving total parenteral nutrition: An audit of practice at a tertiary UK centre.

BACKGROUND & AIMS: The key to preventing refeeding syndrome (RS) is identifying and appropriately managing patients at risk. We evaluated our clinical management of RS risk in patients starting total parenteral nutrition (TPN). METHODS: Patients commencing TPN at University College London Hospital between January and July 2015 were prospectively followed-up for 7-days. Eighty patients were risk assessed for RS and categorized into risk groups. High and low risk RS groups were compared focussing on the onset of biochemical features of RS (hypophosphatemia, hypokalaemia and hypomagnesemia) and initial clinical assessment. Statistical analysis was conducted using t-tests and Mann-Whitney U tests. RESULTS: Sixty patients (75%) were identified as high-risk for RS and received lower initial calories (12.8 kcal/kg/day, p < 0.05). All high-risk patients received a high potency vitamin preparation compared to 35% in the low risk group (p < 0.05). Daily phosphate, magnesium and potassium plasma levels were monitored for seven days in 25%, 30% and 53.8% of patients, respectively. Hypophosphatemia developed in 30% and hypomagnesaemia and hypokalaemia in 27.5% of all patients. Approximately 84% of patients had one or more electrolyte abnormalities, which occurred more frequently in high-risk RS patients (p < 0.05). Low risk patients developed mild hypophosphatemia at a much lower percentage than high-risk RS (20% vs 33.3%, respectively). CONCLUSION: A significant proportion of patients commencing TPN developed biochemical features of RS (but no more serious complications) despite nutritional assessment, treatment, and follow up in accordance with national recommendations. High vs low risk RS patients were more likely to have electrolyte abnormalities after receiving TPN regardless of preventative measures. Additional research is required to further optimise the initial nutritional approach to prevent RS in high-risk patients.

Evaluation of Revised International Staging System (R-ISS) for transplant-eligible multiple myeloma patients.

The International Myeloma Working Group has proposed the Revised International Staging System (R-ISS) for risk stratification of multiple myeloma (MM) patients. There are a limited number of studies that have validated this risk model in the autologous stem cell transplant (ASCT) setting. In this retrospective study, we evaluated the applicability and value for predicting survival of the R-ISS model in 134 MM patients treated with new agents and ASCT at the Mayo Clinic in Arizona and the University Hospital of Salamanca in Spain. The patients were reclassified at diagnosis according to the R-ISS: 44 patients (33%) had stage I, 75 (56%) had stage II, and 15 (11%) had stage III. After a median follow-up of 60 months, R-ISS assessed at diagnosis was an independent predictor for overall survival (OS) after ASCT, with median OS not reached, 111 and 37 months for R-ISS I, II and III, respectively (P < 0.001). We also found that patients belonging to R-ISS II and having high-risk chromosomal abnormalities (CA) had a significant shorter median OS than those with R-ISS II without CA: 70 vs. 111 months, respectively. Therefore, this study lends further support for the R-ISS as a reliable prognostic tool for estimating survival in transplant myeloma patients and suggests the importance of high-risk CA in the R-ISS II group.

Performance Status, Prognostic Scoring, and Parenteral Nutrition Requirements Predict Survival in Patients with Advanced Cancer Receiving Home Parenteral Nutrition.

We describe a cohort of Home Parenteral Nutrition (HPN) patients with advanced cancer in order to identify factors affecting prognosis. Demographic, anthropometric, biochemical and medical factors, Karnofsky Performance Status (KPS), Glasgow Prognostic Score (GPS), and PN requirements were recorded. Univariate and multivariate analyses were performed including Kaplan-Meier curves, Cox Regression, and correlation analyses. In total, 107 HPN patients (68 women, 39 men, mean age 57 yr) with advanced cancer were identified. The main indications for HPN were bowel obstruction (74.3%) and high output ostomies (14.3%). Cancer cachexia was present in 87.1% of patients. The hazard ratio (HR) for upper gastrointestinal and "other" cancers vs. gynaecological malignancy was 1.75 (p = 0.077) and 2.11 (p = 0.05), respectively. KPS score, GPS, PN volume, and PN potassium levels significantly predicted survival (HRKPS ≥50 vs <50 = 0.47; HRGPS = 2 vs. GPS = 0 = 3.19). In multivariate analysis, KPS and GPS remained significant predictors (p < 0.05), whilst PN volume reached borderline significance (p = 0.094). Survival was not significantly affected by the presence of metastatic disease, previous or concurrent surgery, chemo-radiotherapy, or indication for HPN (p > 0.05). Most patients passed away in their homes or hospice (77.9%). Performance status, prognostic scoring, and PN requirements may predict survival in patients with advanced cancer receiving HPN.

Precision Medicine in Myeloma: Challenges in Defining an Actionable Approach.

Recently, large sequencing studies have provided insights into the mutational landscape of multiple myeloma (MM), identifying actionable mutations and giving a precious opportunity for exploring new targeted therapies. The main goal of precision medicine, matching patients with the right drug, seems to be closer than ever. However, no targeted therapies in MM are approved yet. Several clinical trials testing targeted drugs and enrolling patients with MM are currently ongoing and will provide predictive biomarkers that might support clinical decision making. In this review, we evaluate the evidence supporting the implementation of precision medicine in MM and we discuss the challenges that should be dealt with in this imminent and promising new era.

IAP antagonists induce anti-tumor immunity in multiple myeloma.

The cellular inhibitors of apoptosis (cIAP) 1 and 2 are amplified in about 3% of cancers and have been identified in multiple malignancies as being potential therapeutic targets as a result of their role in the evasion of apoptosis. Consequently, small-molecule IAP antagonists, such as LCL161, have entered clinical trials for their ability to induce tumor necrosis factor (TNF)-mediated apoptosis of cancer cells. However, cIAP1 and cIAP2 are recurrently homozygously deleted in multiple myeloma (MM), resulting in constitutive activation of the noncanonical nuclear factor (NF)-κB pathway. To our surprise, we observed robust in vivo anti-myeloma activity of LCL161 in a transgenic myeloma mouse model and in patients with relapsed-refractory MM, where the addition of cyclophosphamide resulted in a median progression-free-survival of 10 months. This effect was not a result of direct induction of tumor cell death, but rather of upregulation of tumor-cell-autonomous type I interferon (IFN) signaling and a strong inflammatory response that resulted in the activation of macrophages and dendritic cells, leading to phagocytosis of tumor cells. Treatment of a MM mouse model with LCL161 established long-term anti-tumor protection and induced regression in a fraction of the mice. Notably, combination of LCL161 with the immune-checkpoint inhibitor anti-PD1 was curative in all of the treated mice.

Abacavir-reactive memory T cells are present in drug naïve individuals.

BACKGROUND: Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population. METHODS: To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling. RESULTS: Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells. CONCLUSIONS: We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection.

AKT as a therapeutic target in multiple myeloma.

INTRODUCTION: Multiple myeloma remains an incurable malignancy with poor survival. Novel therapeutic approaches capable of improving outcomes in patients with multiple myeloma are urgently required. AKT is a central node in the phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin signaling pathway with high expression in advanced and resistant multiple myeloma. AKT contributes to multiple oncogenic functions in multiple myeloma which may be exploited therapeutically. Promising preclinical data has lent support for pursuing further development of AKT inhibitors in multiple myeloma. Lead drugs are now entering the clinic. AREAS COVERED: The rationale for AKT inhibition in multiple myeloma, pharmacological subtypes of AKT inhibitors in development, available results of clinical studies of AKT inhibitors and suitable drug partners for further development in combination with AKT inhibition in multiple myeloma are discussed. EXPERT OPINION: AKT inhibitors are a welcome addition to the armamentarium against multiple myeloma and promising clinical activity is being reported from ongoing trials in combination with established and/or novel treatment approaches. AKT inhibitors may be set to improve patient outcomes when used in combination with synergistic drug partners.

HLA Class I restricted CD8+ and Class II restricted CD4+ T cells are implicated in the pathogenesis of nevirapine hypersensitivity.

OBJECTIVES: This study sought to examine nevirapine hypersensitivity (NVP HSR) phenotypes and their relationship with differing major histocompatibility complex (MHC) Class I and Class II alleles and the associated CD4 and CD8 T-cell NVP-specific responses and their durability over time. METHODS: A retrospective cohort study compared HIV-positive patients with NVP HSR, defined by fever and hepatitis and/or rash, with those tolerant of NVP for more than 3 months. Covariates included class I (HLA-A, B, C) and class II (HLA-DR) alleles. Cellular studies examined NVP-specific CD4 and CD8 T-cell responses by interferon-gamma (IFNγ) ELISpot assay and intracellular cytokine staining (ICS). RESULTS: NVP HSR occurred in 19 out of 451 (4%) NVP-exposed individuals between March 1993 and December 2011. HLA associations were phenotype dependent with HLA-DRB1*01 : 01 associated with hepatitis (P = 0.02); HLA-B*35 : 01 and HLA-Cw4 associated with cutaneous NVP HSR (P = 0.001, P = 0.01), and HLA-Cw*08 was associated with NVP HSR with eosinophilia (P = 0.04) and multisystemic NVP HSR (P = 0.02). NVP-specific INFγ responses waned significantly more than 3 months from the original reaction and were diminished or completely abrogated when either CD4 or CD8 T cells were depleted from the peripheral blood mononuclear cells culture. CONCLUSION: The association of specific class I and II allele pairings with specific phenotypes of NVP HSR, and cellular studies showing both CD4 and CD8 T-cell NVP-specific responses suggest that specific combinations of NVP reactive class I restricted CD8 and class II restricted CD4 T cells contribute to the immunopathogenesis of NVP HSR.

Randomised controlled trial comparing European standard class 1 to class 2 compression stockings for ulcer recurrence and patient compliance.

The aim of this study was to determine the rate of venous ulcer recurrence and the level of compliance in patients wearing European class 1 or class 2 compression stockings. A total of 100 patients with healed venous leg ulcers were recruited, and were randomised to either class 1 (n = 50) or class 2 (n = 50) compression stockings. Follow-up was at 1 week, 3, 6, 9 and 12 months to monitor ulcer recurrence and compliance. Patients had a duplex scan to identify the source of venous incompetence. The rate of ulcer recurrence after 12 months was 16·1%, and the difference in recurrence rate between classes was not statistically significant (P = 0·287) although greater numbers in class 1 developed a recurrence. Participants (88·9%) were compliant; non-compliant patients were at a significantly greater risk of recurrence (P≤ 0·0001). Thirteen patients had both superficial and deep incompetence; those randomised to class 1 stockings (n = 4) developed ulcer recurrence. Patients with a history of multiple episodes of ulceration were more likely to develop a recurrence (P = 0·001). The lowest venous ulcer recurrence rates were seen in patients who were compliant with hosiery regardless of the compression level. Patients with both superficial and deep incompetence had a lower rate of recurrence with class 2 compression.

Posterior pharyngeal candidiasis in the absence of clinically overt oral involvement: a cross-sectional study.

PURPOSE: Although oropharyngeal candidiasis is associated with inhaled corticosteroid (ICS) usage, there is sparse data on the prevalence of posterior pharyngeal candidiasis in those without any detectable oral candidiasis on clinical examination. We systematically investigated the relationship between oral candidiasis on clinical examination and the presence of posterior pharyngeal candidiasis at bronchoscopy. METHODS: We conducted a cross-sectional study on a convenience sample of 100 patients undergoing bronchoscopy at our institution. Patients were assessed for symptoms of and risk factors for candida infection and had an examination of their oropharynx for evidence of candidiasis before bronchoscopy. They subsequently had a detailed assessment for posterior candidiasis at bronchoscopy. We performed a posteriori subgroup analysis, which focused solely on those patients on ICS maintenance therapy. RESULTS: Median age was 54.7 (27-84) years, and 55 patients were male; 47 % of patients were on ICS, and 20 % of this cohort received recent oral corticosteroids. Twenty-eight percent of this convenience sample had posterior pharyngeal candidiasis; however, only 10.7 % (3/28) of these patients had clinically detectable oral candidiasis on clinical examination before bronchoscopy. Factors that were independently associated with the presence of pharyngeal candidiasis at bronchoscopy were OR (95 % CI) ICS usage 6.9 (2.5-19.2), particularly fluticasone usage 6.8 (2.62-17.9) and the presence of dysphonia 3.2 (1.3-8.0). In the subgroup analysis of ICS usage, posterior pharyngeal candidiasis was correlated with the presence of dysphonia but was not independently associated with fluticasone or budesonide dosage. CONCLUSIONS: This study demonstrates that posterior pharyngeal candidiasis in the absence of clinically overt oral candidiasis is frequent amongst ICS users. A history of ICS use, particularly fluticasone usage, as well as the presence of dysphonia are associated with posterior pharyngeal candidiasis at bronchoscopy, even in the absence of clinically overt oral involvement.

Perifosine--a new option in treatment of acute myeloid leukemia?

INTRODUCTION: Perifosine is a novel targeted oral Akt inhibitor. In preclinical leukemia models, perifosine has an independent cytotoxic potential but also synergizes well with other rationally selected targeted agents. The evidence from clinical trials supporting the use of perifosine in the therapy of leukemias is limited. The optimal dose and schedule have yet to be defined. However, given its favorable toxicity profile and mechanism of action, the therapeutic potential of perifosine should be evaluated in well-designed clinical trials. AREAS COVERED: The role of the phosphatidylinositol-3 kinase (PI3K)/Akt zpathway in normal cells, cancer and leukemias is discussed. The mechanism of action of perifosine and the basic information on the development and chemical properties are summarized. The evidence from in vivo and in vitro studies is presented. The efficacy and side effect profile are summarized. EXPERT OPINION: The safety and tolerability profile of perifosine are satisfactory. The evidence from clinical trials in patients with leukemias is very limited. The preclinical data are encouraging. Perifosine has the potential to play a role in the treatment of leukemias in the future. Its role needs to be confirmed in clinical trials.