Risk factors for mortality in Down syndrome.

BACKGROUND: Down syndrome is a genetic condition that contributes to a significantly shorter life expectancy compared with the general population. We investigated the most common comorbidities in a population of acute hospital patients with Down syndrome and further explored what the most common risk factors for mortality are within this population. METHOD: From our database of one million patients admitted to National Health Service (NHS) Trusts in northern England, we identified 558 people who had Down syndrome. We compared this group with an age- and gender-matched control group of 5580 people. RESULTS: The most prevalent comorbid diseases within the Down's population were hypothyroidism (22.9%) and epilepsy (20.3%). However, the conditions that had the highest relative risks (RRs) in the Down's population were septal defects and dementia. Respiratory failure, dementia and pneumonia were the most significantly related comorbidities to mortality in the Down syndrome population. In the control population, respiratory failure, dementia and renal failure were the most significant disease contributors. When these contributors were analysed using multivariate analysis, heart failure, respiratory failure, pneumonia and epilepsy were the identified risk factors for in-hospital mortality in the Down syndrome population. Respiratory failure was the sole risk factor for mortality in the Down syndrome population [RR = 9.791 (1.6-59.9) P ≤ 0.05], when compared with the risk factors for mortality in the control population. CONCLUSIONS: There is significant medical morbidity in Down syndrome. This morbidity contributes to the lower life expectancy. Respiratory failure is a risk factor for mortality in Down syndrome. We need to thoroughly investigate people with Down syndrome to ensure any treatable illnesses are well managed.

Phase I/II trial of a dendritic cell vaccine transfected with DNA encoding melan A and gp100 for patients with metastatic melanoma.

This trial tested a dendritic cell (DC) therapeutic cancer vaccine in which antigen is loaded using a novel non-viral transfection method enabling the uptake of plasmid DNA condensed with a cationic peptide. Proof of principle required the demonstration of diverse T lymphocyte responses following vaccination, including multiple reactivities restricted through both major histocompatibility complex (MHC) class I and II. Patients with advanced melanoma were offered four cycles of vaccination with autologous DC expressing melan A and gp100. Disease response was measured using Response Evaluation Criteria in Solid Tumours. Circulating MHC class I- and II-restricted responses were measured against peptide and whole antigen targets using interferon-γ ELIspot and enzyme-linked immunosorbent assay assays, respectively. Responses were analyzed across the trial population and presented descriptively for some individuals. Twenty-five patients received at least one cycle. Vaccination was well tolerated. Three patients had reduction in disease volume. Across the trial population, vaccination resulted in an expansion of effector responses to both antigens, to the human leukocyte antigen A2-restricted modified epitope, melan A ELAGIGILTV, and to a panel of MHC class I- and II-restricted epitopes. Vaccination with mature DC non-virally transfected with DNA encoding antigen had biological effect causing tumour regression and inducing diverse T lymphocyte responses.

Selective axillary node sampling and radiotherapy to the axilla in the management of breast cancer.

AIMS: Axillary treatment for patients with early-stage breast cancer can be associated with considerable morbidity. Techniques, such as axillary node sampling (ANS) and, more recently, sentinel node biopsy, in combination with radiotherapy have the potential to reduce toxicity. A retrospective review of axillary treatment in patients with early-stage breast cancer treated at our institution between 1997 and 2003 was carried out to assess the outcome and morbidity of ANS in combination with radiotherapy. MATERIALS AND METHODS: The treatment policy was to carry out four-node, Edinburgh-style ANS except in those cases with either palpably enlarged nodes or cytological confirmation of involvement or with clinically obvious node involvement at surgery when level 2 axillary node clearance (ANC) was carried out. Patients with involved nodes after ANS received postoperative axillary radiotherapy. RESULTS: In total, 381 patients were included, 331 received ANS and 50 received ANC. The median follow-up was 6.5 years and overall survival at 5 years was 84%. Pathologically involved nodes were found in 152/331 (50%) ANS patients and 43/50 (86%) ANC patients. The rate of local recurrence (breast or chest wall) at 5 years was 4% (95% confidence interval 1-17%) in the ANC group and 2% (95% confidence interval 1-4%) in the ANS group. The nodal recurrence rate of those undergoing ANS was 3% (11/331) compared with 6% (3/50) for those treated by ANC. The rate of clinically significant lymphoedema at 5 years was significantly higher (P=0.01) in the ANC arm: 18% (95% confidence interval 9-32%) compared with 5% (95% confidence interval 3-8%) in those treated by ANS. Thirty-one cases received additional supraclavicular fossa irradiation because of the involvement of more than four nodes on ANS, which may not have been available with sentinel node biopsy and has implications for current practice. CONCLUSIONS: Selective ANS with the removal of a minimum of four nodes guides optimal locoregional treatment with good local control rates, low overall morbidity and may obviate the need for a second surgical procedure.

Sciatic nerve injury caused by pre-operative intraneural injection of local anaesthetic during total hip replacement.

We report a case of iatrogenic sciatic nerve injury caused by pre-operative intraneural injection of local anaesthetic at total hip replacement. To our knowledge, this is unreported in the orthopaedic literature. We consider sacral nerve blockade in patients undergoing total hip replacement to be undesirable and present guidelines for the management of peri-operative sciatic nerve injury.

Cardiotoxicity Associated with Nicotinamide Phosphoribosyltransferase Inhibitors in Rodents and in Rat and Human-Derived Cells Lines.

Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein that functions as an enzyme, cytokine, growth factor and hormone. As a target for oncology, NAMPT is particularly attractive, because it catalyzes the rate-limiting step in the salvage pathway to generate nicotinamide adenine dinucleotide (NAD), a universal energy- and signal-carrying molecule involved in cellular energy metabolism and many homeostatic functions. Inhibition of NAMPT generally results in NAD depletion, followed by ATP reduction and loss of cell viability. Herein, we describe NAMPT inhibitor (NAMPTi)-induced cardiac toxicity in rodents following short-term administration (2-7 days) of NAMPTi's. The cardiac toxicity was interpreted as a functional effect leading to congestive heart failure, characterized by sudden death, thoracic and abdominal effusion, and myocardial degeneration. Based on exposures in the initial in vivo safety rodent studies and cardiotoxicity observed, we conducted studies in rat and human in vitro cardiomyocyte cell systems. Based on those results, combined with human cell line potency data, we demonstrated the toxicity is both on-target and likely human relevant. This toxicity was mitigated in vitro by co-administration of nicotinic acid (NA), which can enable NAD production through the NAMPT-independent pathway; however, this resulted in only partial mitigation in in vivo studies. This work also highlights the usefulness and predictivity of in vitro cardiomyocyte assays using human cells to rank-order compounds against potency in cell-based pharmacology assays. Lastly, this work strengthens the correlation between cardiomyocyte cell viability and functionality, suggesting that these assays together may enable early assessment of cardiotoxicity in vitro prior to conduct of in vivo studies and potentially reduce subsequent attrition due to cardiotoxicity.

Case of the month: Dislodged tracheo-oesophageal valve: importance of rapid replacement or stenting.

Dislodgement of a tracheo-oesophageal prosthesis needs prompt action to ensure patency and prevent aspiration in patients with total laryngectomy. Failure to do so may lead to an unnecessary repeat tracheo-oesophageal puncture. This case report is about a patient who needed a repeat procedure under general anaesthetic. It highlights the need for emergency physicians to be aware of this not uncommon event in a patient with a laryngectomy and to refer them immediately for ENT review.

Impact of cardiovascular risk factors and disease on length of stay and mortality in patients with acute coronary syndromes.

BACKGROUND: Traditional risk factors for cardiovascular disease (CVD) have been thoroughly investigated. We aimed to investigate the impact of comorbid cardiovascular risk factors and diseases on length of stay (LOS) and mortality in patients presenting with acute coronary syndromes (ACS). METHODS: We examined prevalence of CVD, LOS and mortality from 25,287 consecutive admissions for ACS from seven hospitals across North West England between 2000 and 2013 using the ACALM (Algorithm for Comorbidities, Associations, Length of stay and Mortality) protocol using ICD-10 and OPCS-4 coding systems. RESULTS: Mean LOS was 7.0days and there were 9653 (38.2%) deaths in the ACS cohort over the 13-year period. Hypertension and hyperlipidaemia were associated with decreased LOS (6.95 and 4.8days respectively, P<0.001) and mortality (36.8% and 19.4% respectively, P<0.001), as was angina pectoris (5.4days and 33.5%, P<0.001). Type 2 diabetes was associated with increased LOS and mortality (7.8days, P<0.05; 44.4%, P<0.001), whereas type 1 diabetes was associated with increased mortality only (7.0days, P=0.42; 41.3%, P<0.001). Other concomitant CVD was associated with an increased LOS and mortality: peripheral vascular disease (8.6days, P<0.05; 53%, P<0.001), atrial fibrillation (10.9days, P<0.001; 63.5%, P<0.001), cerebrovascular disease (15.9days, P<0.001; 76%, P<0.001), heart failure (11days, P<0.001; 69.9%, P<0.001), and ischaemic heart disease (6.7days, P<0.001; 38.7%, P<0.05). CONCLUSION: CVD risk factors have a significant and varied impact on LOS and mortality in patients with ACS and it may be inappropriate to group them when assessing in-hospital risk. These factors should be used to identify patients at an increased risk of prolonged admissions and death post-ACS, and services should be directed accordingly.

Anatomy of the terminal branch of the posterior circumflex humeral artery: relevance to the deltopectoral approach to the shoulder.

AIMS: Despite the expansion of arthroscopic surgery of the shoulder, the open deltopectoral approach is increasingly used for the fixation of fractures and arthroplasty of the shoulder. The anatomy of the terminal branches of the posterior circumflex humeral artery (PCHA) has not been described before. We undertook an investigation to correct this omission. PATIENTS AND METHODS: The vascular anatomy encountered during 100 consecutive elective deltopectoral approaches was recorded, and the common variants of the terminal branches of the PCHA are described. RESULTS: In total, 92 patients (92%) had a terminal branch that crossed the space between the deltoid and the proximal humerus and which was therefore vulnerable to tearing or avulsion during the insertion of the blade of a retractor during the deltopectoral approach to the shoulder. In 75 patients (75%) there was a single vessel, in 16 (16%) a double vessel and in one a triple vessel. CONCLUSION: The relationship of these vessels to the landmark of the tendon of the insertion of pectoralis major into the proximal humerus is described. Damage to these previously undocumented branches can cause persistent bleeding leading to prolonged surgery and post-operative haematoma and infection, as well as poor visualisation during the procedure. Cite this article: Bone Joint J 2016;98-B:1395-8.

The EEG changes during cardiac arrest: a case report.

This case report of a patient with an irreversible cardiac arrest shows that the amplitude of the EEG, rather than its duration, when it becomes discontinuous, has a closer relationship with a diminished heart rate to a final arrest. These data may be helpful in determining the extent of cerebral demise of patients with a deteriorating cardiac function.

TRI-PLEDs: a case report.

This case report shows an example of TRI-PLEDs, periodic discharges occurring independently on 3 different areas. The phenomenon of the PLED is briefly discussed.

Extramedullary plasmacytoma of the larynx presenting with upper airway obstruction in a patient with long-standing IgD myeloma.

A rare case of upper airway obstruction due to an extramedullary plasmacytoma of the larynx in a patient with long-standing IgD myeloma is presented. Reports of patients with extramedullary plasmacytomas eventually developing multiple myeloma are common, however, the converse appears to be an extremely rare event. Attention is drawn to the problem of acquiring adequate tissue for diagnostic purposes as well as the use of immunohistochemical staining techniques. The patient required an urgent tracheostomy and was treated with radiotherapy.

Sudden onset bilateral sensorineural hearing loss: a manifestation of occult breast carcinoma.

Diffuse infiltration of the meninges by metastatic carcinoma (meningeal carcinomastosis) is a potential complication of systemic malignancy. It may present with a variety of neurological symptoms as any aspect of the neuraxis can be affected. Often there is a history of pre-existing malignancy. The authors describe a case with an initial presentation of sudden onset profound bilateral sensorineural hearing loss. The underlying pathology was found to be an occult breast carcinoma, a previously unreported finding. The role of cerebrospinal fluid cytology and radio-imaging in diagnosis is discussed. All previously reported cases of sudden hearing loss and meningeal carcinomatosis are reviewed.

Osseo-integration in Paget's disease: the bone-anchored hearing aid in the rehabilitation of Pagetic deafness.

The first report of a patient with gross Paget's disease and progressive hearing loss who successfully underwent hearing rehabilitation with an osseo-integrated hearing aid is presented. The otological manifestations of Paget's disease and the principles of osseo-integration are discussed. The use of a bone-anchored hearing aid (BAHA) in selected patients with Paget's disease can provide useful amplification and hearing rehabilitation.

Actinomycosis of the post-cricoid space: an unusual cause of dysphagia.

Cervicofacial actinomycosis is known to affect many soft tissues and bony structures in the head and neck. However to the authors' knowledge, actinomycosis of the post-cricoid region has not been previously reported. A case of a 74-year-old male who developed actinomycosis of the post-cricoid region after radiotherapy for a laryngeal carcinoma is presented. Actinomycosis should be considered in the differential diagnosis of dysphagia following radiotherapy for squamous cell carcinoma of the larynx, as early treatment is likely to result in a favourable outcome.

Current practices of cocaine administration by UK otorhinolaryngologists.

The aim of this study was to determine which anaesthetic and vasoconstrictor preparations UK Otorhinolaryngologists use for rhinological surgery, with particular reference to cocaine and adrenaline. The incidence and types of adverse reactions to cocaine were also recorded. A postal survey of all BAO-HNS consultant members was performed. Of the 360 consultant surgeons included in the survey, the majority still use peri-operative cocaine on a regular basis, 66 per cent use cocaine and adrenaline together and more than 40 per cent use cocaine in paediatric patients. Sixteen per cent of respondents did not use cocaine. Only 11 per cent of surgeons had experienced cocaine toxicity in their patients, with only one recorded case of mortality. Most surgeons in the UK use cocaine because of the superior operative field it provides and because they consider it to be safe even with adrenaline. The actual incidence of adverse reactions to cocaine is low, with serious complications being less common than the risks from general anaesthesia. Cocaine remains a valuable agent in the armamentarium of the rhinologist.

The viability of cells obtained using the Reamer-Irrigator-Aspirator system and in bone graft from the iliac crest.

We hypothesised that cells obtained via a Reamer-Irrigator-Aspirator (RIA) system retain substantial osteogenic potential and are at least equivalent to graft harvested from the iliac crest. Graft was harvested using the RIA in 25 patients (mean age 37.6 years (18 to 68)) and from the iliac crest in 21 patients (mean age 44.6 years (24 to 78)), after which ≥ 1 g of bony particulate graft material was processed from each. Initial cell viability was assessed using Trypan blue exclusion, and initial fluorescence-activated cell sorting (FACS) analysis for cell lineage was performed. After culturing the cells, repeat FACS analysis for cell lineage was performed and enzyme-linked immunosorbent assay (ELISA) for osteocalcin, and Alizarin red staining to determine osteogenic potential. Cells obtained via RIA or from the iliac crest were viable and matured into mesenchymal stem cells, as shown by staining for the specific mesenchymal antigens CD90 and CD105. For samples from both RIA and the iliac crest there was a statistically significant increase in bone production (both p < 0.001), as demonstrated by osteocalcin production after induction. Medullary autograft cells harvested using RIA are viable and osteogenic. Cell viability and osteogenic potential were similar between bone grafts obtained from both the RIA system and the iliac crest.

Type-2 diabetes mellitus in schizophrenia: increased prevalence and major risk factor of excess mortality in a naturalistic 7-year follow-up.

OBJECTIVE: Physical co-morbidity including type 2 diabetes mellitus is more prevalent in patients with schizophrenia compared to the general population. However, there is little consistent evidence that co-morbidity with diabetes mellitus and/or other diseases leads to excess mortality in schizophrenia. Thus, we investigated whether co-morbidity with diabetes and other somatic diseases is increased in schizophrenics, and if these are equally or more relevant predictors of mortality in schizophrenia than in age- and gender-matched hospitalised controls. METHODS: During 2000-2007, 679 patients with schizophrenia were admitted to University Hospital Birmingham NHS Trust. Co-morbidities were compared with 88,778 age- and gender group-matched hospital controls. Predictors of mortality were identified using forward Cox regression models. RESULTS: The prevalence of type 2 diabetes mellitus was increased in schizophrenia compared to hospitalised controls (11.3% versus 6.3%). The initial prevalence of type 2 diabetes mellitus was significantly higher in the 100 later deceased schizophrenic patients (24.0%) than in those 579 surviving over 7 years (9.2%). Predictors of mortality in schizophrenia were found to be age (relative risk [RR] = 1.1/year), type 2 diabetes mellitus (RR = 2.2), pneumonia (RR = 2.7), heart failure (RR = 2.9) and chronic renal failure (RR = 3.2). The impact of diabetes mellitus on mortality was significantly higher in schizophrenia than in hospital controls (RR = 2.2 versus RR = 1.1). In agreement, deceased schizophrenics had significantly suffered more diabetes mellitus than deceased controls (24.0 versus 10.5%). The relative risks of mortality for other disorders and their prevalence in later deceased subjects did not significantly differ between schizophrenia and controls. CONCLUSION: Schizophrenics have more and additionally suffer more from diabetes: co-morbidity with diabetes mellitus is increased in schizophrenia in comparison with hospital controls; type 2 diabetes mellitus causes significant excess mortality in schizophrenia. Thus, monitoring for and prevention of type 2 diabetes mellitus is of utmost relevance in hospitalised patients with schizophrenia.

Co-composting of physic nut (Jatropha curcas) deoiled cake with rice straw and different animal dung.

To address the dispensing of this growing volume, a study on utilization of jatropha (Jatropha curcas) deoiled cake through compost production was carried out. The deoiled cake was composted with rice straw, four different animal dung (cow dung, buffalo dung, horse dung and goat dung) and hen droppings in different proportions followed by assessment, and comparison of biochemical characteristics among finished composts. Nutrient content in finished compost was within the desired level whereas metals such as copper, lead and nickel were much below the maximum allowable concentrations. Although a few finished material contained phorbol ester (0.12 mg/g), but it was far below the original level found in the deoiled cake. Such a study indicates that a huge volume of jatropha deoiled cake can be eliminated through composting.