Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer.

Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.

Biochar as a sustainable alternative to carbon black in agricultural mulch films.

Examples of biochar as an alternative to traditional plastic fillers, like carbon black, are numerous and growing. However, in the agricultural mulch film application, both the polymer and its fillers are pushed to their mechanical limit to obtain an effective product, using the least amount of plastic. Through a combined techno-economic analysis (TEA) and life cycle assessment (LCA), this study characterizes the use of carbon-negative biochar as an opacity filler in mulch film applications. Due to its larger particle size, the biochar demands additional thickness to achieve equivalent opacity as carbon black in films. A thicker film translates to additional polymer demand, and a significant increase in price and environmental impact. A comparable formulation for an equal price ($623 per mulched ha) as a 2.6 wt % carbon black with 25 µm thickness was derived, needing 15 wt % biochar and a thickness of 30 µm. The biochar formulation resulted in a slightly higher global warming potential (3% increase), but much larger impact in the land use category (+339%), and the sample was deemed not fit for use in the intended mulch application. These results indicate that in applications where the polymeric matrix and its fillers are pushed to their mechanical limit, the displacement of traditional fillers by biochar is challenging. However, biochar derived from waste biomass (thus reducing land use impact) remains a valid, environmentally beneficial solution to displace traditional fillers for non-extreme plastic uses (commodity plastics) and thicker composites.

Effects of 24-week prebiotic intervention on self-reported upper respiratory symptoms, gastrointestinal symptoms, and markers of immunity in elite rugby union players.

OBJECTIVES: Elite rugby union players face numerous physiological and psychological stressors which can increase upper respiratory and gastrointestinal illness risk, and in turn can compromise training and competitive performance. This study aimed to investigate the effect of daily prebiotic supplementation on upper respiratory symptoms, gastrointestinal symptoms, and markers of immune function in elite rugby union players. METHODS: Thirty-three elite rugby union players were randomly assigned to consume a prebiotic (2.8 g/day galactooligosaccharide) or placebo (2.8 g/day maltodextrin), daily for 168 days under double-blind conditions. Participants completed daily and weekly questionnaires for self-reported upper respiratory and gastrointestinal symptoms respectively. Blood and saliva samples were collected at 0, 84, and 168 days for assessment of plasma TNF-α and CRP, and saliva IgA respectively. RESULTS: The prebiotic group experienced a 2-day reduction in upper respiratory symptom duration (P = 0.045). Gastrointestinal symptom severity and incidence were lower in the prebiotic group compared to the placebo group (P < 0.001, P = 0.041) respectively. Salivary immunoglobulin A secretion rate was 42% greater in the prebiotic group compared to the placebo group at day 168 (P = 0.004), no differences in CRP and TNF-α were found (P > 0.05). CONCLUSION: A 168-day dietary prebiotic intervention reduced the duration of upper respiratory symptoms and reduced the incidence and severity of gastrointestinal symptoms in elite rugby union players. These findings suggest that seasonal prebiotic interventions may be beneficial for reducing illness in elite rugby union players, improving their availability to train and compete.Key pointsElite athletes are susceptible to upper respiratory symptoms and gastrointestinal symptoms which may impact upon training availability and competition performance.For the first time, this study shows that a dietary prebiotic intervention can reduce the duration of upper respiratory symptoms by 2 days in elite rugby union players.Dietary prebiotic supplementation can improve the incidence and severity of gastrointestinal symptoms experienced by elite rugby union players.Prebiotic supplementation was able to increase salivary IgA secretion after 168 days.These findings can inform practice suggesting that seasonal prebiotic use has the potential to modulate immune function and reduce illness in elite rugby union, which may improve a player's availability to train and compete.The mechanisms by which prebiotics reduce URS and GIS require further research exploration.

Audit of waist measurement methods during statutory diving medical assessments.

BACKGROUND: Measurement of waist circumference is used to assess abdominal fat and risk of heart disease, type 2 diabetes, cancer and stroke. It is performed in several clinical settings for health promotion and medical assessment purposes, including statutory medical assessments where results may influence decisions on fitness to work. Under the Diving at Work Regulations 1997, working divers must have an annual assessment of their fitness to dive performed by an approved medical examiner of divers (AMED), appointed by the Health and Safety Executive (HSE). The assessment includes measurement of height, weight and waist circumference, the latter used as an indicator of central adiposity and associated health risks. AIMS: To establish the practice of AMEDs in measuring waist circumference of working divers undergoing medical assessment to determine their fitness to dive. METHODS: Ninety-seven AMEDs were sent a questionnaire and asked to describe their current practice in measuring waist circumference. The response rate was 79%. The audit standard used was the consensus document published by the World Health Organization (WHO). RESULTS: Of the 77 responses, 76 were completed sufficiently to allow analysis. When the waist was measured, there was consistency in the diver's level of clothing, stage of breathing and posture for the procedure but variability in the site of measurement. Only 7/76 (9%) respondents carried out waist measurement fully in line with WHO guidance. CONCLUSIONS: The audit has identified that there is a need for guidance for AMEDs on measuring waist circumference in the statutory medical assessment of working divers.

An international multidisciplinary peer-driven consensus on the optimal use of hemostatic powders in surgical practice.

Bleeding is a consequence of insufficient hemostasis and excessive bleeding at a surgical site is associated with an increased risk of post-operative infection, transfusion and re-operation, in addition to increased hospital length of stay and costs. Surgeons employ a range of methods to achieve hemostasis, including topical hemostatic agents of differing composition and properties. Hemostatic powders are a sub-group of topical hemostats, which can be used in helping as adjuncts to manage troublesome bleeding in a variety of situations. As this technology is relatively new and potentially not well known by the broad surgical community, no specific guidelines or recommendations for the optimal use of hemostatic powders in surgery currently exist. A steering group throughout Europe of multidisciplinary surgeons, expert in hemostasis and hemostatics, identified from literature and from personal experience, five key topics. When to use hemostatic powder, the evidence for use, benefits of use, safety remarks and considerations in various surgical specialties. Thirty-seven statements were subsequently drawn from these five key topics. An online survey was sent to 128 high-volume surgeons working in breast surgery, gynaecological and obstetric surgery, general and emergency surgery, thoracic surgery and urological surgery in Europe to assess agreement (consensus) with these statements. Consensus was defined as high if ≥ 75% and very high if ≥ 90% of respondents agreed with a statement. A total of 79 responses were received and consensus among the surgical experts was very high in 27 (73%) statements, high in 8 (22%) statements and was not achieved in 2 (5%) statements. Based on the consensus scores, the steering group produced 16 key recommendations which they considered could improve patient outcomes by reducing post-operative bleeding and its associated complications using hemostatic powder.

OVPSYCH2: A randomized controlled trial of psychological support versus standard of care following chemotherapy for ovarian cancer.

BACKGROUND: Fear of disease progression (FOP) is a rational concern for women with Ovarian Cancer (OC) and depression is also common. To date there have been no randomized trials assessing the impact of psychological intervention on depression and FOP in this patient group. PATIENTS AND METHODS: Patients with primary or recurrent OC who had recently completed chemotherapy were eligible if they scored between 5 and 19 on the PHQ-9 depression and were randomized 1:1 to Intervention (3 standardized CBT-based sessions in the 6-12 weeks post-chemotherapy) or Control (standard of care). PHQ-9, FOP-Q-SF, EORTC QLQ C30 and OV28 questionnaires were then completed every 3 months for up to 2 years. The primary endpoint was change in PHQ-9 at 3 months. Secondary endpoints were change in other scores at 3 months and all scores at later timepoints. RESULTS: 182 patients registered; 107 were randomized; 54 to Intervention and 53 to Control; mean age 59 years; 75 (70%) had completed chemotherapy for primary and 32 (30%) for relapsed OC and 67 patients completed both baseline and 3-month questionnaires. Improvement in PHQ-9 was observed for patients in both study arms at three months compared to baseline but there was no significant difference in change between Intervention and Control. A significant improvement on FOP-Q-SF scores was seen in the Intervention arm, whereas for those in the Control arm FOP-Q-SF scores deteriorated at 3 months (intervention effect = -4.4 (-7.57, -1.22), p-value = 0.008). CONCLUSIONS: CBT-based psychological support provided after chemotherapy did not significantly alter the spontaneously improving trajectory of depression scores at three months but caused a significant improvement in FOP. Our findings call for the routine implementation of FOP support for ovarian cancer patients.

Pulmonary Metastasectomy in Colorectal Cancer: updated analysis of 93 randomized patients - control survival is much better than previously assumed.

AIM: Lung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5-year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial. METHOD: Multidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two-arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention-to-treat analysis. RESULTS: From 2010 to 2016, 93 participants were randomized. These patients were 35-86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1-6.6) years compared with 3.8 (95% CI: 3.1-4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56-1.56). Use of chemotherapy or local ablation was infrequent and similar in each group. CONCLUSION: Patients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single-arm follow-up studies. The groups were well matched with features similar to those reported in case series.

Cutting through the fat: a retrospective analysis of clinical outcomes, cost, and quality of life with the addition of panniculectomy to ventral hernia repair in overweight patients.

BACKGROUND: Due to the increased prevalence of overweight patients with ventral hernia, abdominal wall reconstruction combining ventral hernia repair (VHR) with panniculectomy (VHR-PAN) in overweight patients is increasingly considered. We present a retrospective comparison between VHR-PAN and VHR alone in overweight patients by examining costs, clinical outcomes, and quality of life (QoL). METHODS: Patients with body mass index (BMI) > 25.0 kg/m2 underwent VHR-PAN or VHR alone between September 2015 and May 2017 with a single surgeon and were matched into cohorts by BMI and age (n = 24 in each cohort). QoL was assessed using the Hernia-related Quality of Life Survey (HerQLes). Cost was assessed using billing data. Statistical analyses were performed using Fisher's exact tests, Mann-Whitney U tests, and regression modeling. RESULTS: Hernia defect size (p = 0.127), operative time (p = 0.140), mesh placement (p = 0.357), and recurrence rates (p = 0.156) did not vary significantly between cohorts at average follow up of one year. 60% of patients completed QoL surveys, with 61% net improvement in VHR-PAN postoperatively (p = 0.042) vs 36% in VHR alone (p = 0.054). Mean total hospitalization costs were higher for VHR alone (p = 0.019). Regression modeling showed no significant independent contribution of procedure performed due to differences in cost, wound complications, or hernia recurrence. CONCLUSIONS: At mean follow up of 2 years, VHR-PAN patients reported a comparable increase in QoL to those who received VHR alone without significantly different cost and complication rates. Concurrent VHR-PAN may therefore be a safe approach for overweight patients presenting with hernia and excess abdominal skin.

The effect of non-steroidal anti-inflammatory drugs on osteosarcoma cells.

OBJECTIVE: Osteosarcoma (OS), an aggressive malignancy, is the most common primary bone tumor in children. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to reduce pain and inflammation. NSAIDs have shown to be toxic to certain malignancies such as colorectal, breast, and pancreatic cancers, but are not well-studied in OS. The purpose of this study is to assess whether ketorolac induces apoptosis in OS cells, compare this to indomethacin, which has been shown to inhibit OS proliferation, and explore the underlying mechanism. MATERIALS AND METHODS: A rat OS cell line (UMR-108) was exposed to various concentrations of ketorolac and indomethacin. Cell viability, cytotoxicity, apoptosis induction, DNA fragmentation and the expression of apoptosis-related markers were examined by MTT assay, colony formation assay, flow cytometry, agarose gel electrophoresis, and Western blot respectively. RESULTS: The results indicated that ketorolac and indomethacin could induce apoptosis of rat OS cells in a dose- and time-dependent manner. Apoptosis was confirmed by cell morphology and annexin positivity. The molecular data showed that NSAIDs affected expression of Bcl-2, survivin, and Poly (ADP-ribose) polymerase-1 (PARP). CONCLUSIONS: These findings demonstrated that NSAIDs induced apoptosis in rat OS cells in vitro. Further research focusing on the potential cytotoxicity of NSAIDs in vivo is needed.

Evaluating unmet needs in patients undergoing surgery for colorectal cancer: a patient reported outcome measures study.

AIM: Patient reported outcome measures (PROMs) are self-reported measures of patients' health status or health-related quality of life at a single point in time. We aimed to evaluate the use of a colorectal PROM and conducted a focus group to further explore this and other unmet needs in our patient population treated surgically for colorectal cancer. METHOD: A multidisciplinary research group consisting of colorectal surgeons, nurse specialists, psychologists, sociologists and patient representatives devised a composite tool of new and existing outcome measures which was piloted in our local population (n = 35). Participants were subsequently invited to attend a semi-structured focus group during which the PROM was reviewed and an unmet needs analysis was performed. Thematic analysis of focus group transcripts was undertaken for emergent themes. RESULTS: Initial consensus was for a tool including the EQ-5D, Functional Assessment of Cancer Therapy - Colorectal (FACT-C), the distress thermometer, a validated measure of stigma, an unmet needs analysis, and questions assessing the psychological impact of cancer. Median and interquartile range values suggested that all metrics were discriminatory with the exception of FACT-C. All participants agreed that the tool was acceptable and reflected the current state of their health and emotions. Thematic analysis of focus group transcripts identified four major themes: physical symptoms, emotional response, information provision and coping mechanisms. CONCLUSION: Through expert consensus, local piloting and patient focus groups we have evaluated a novel PROM for colorectal cancer. Furthermore, through our direct engagement with patients we have identified several unmet needs which we are currently exploring within the clinical service.

Nonrigid reconstruction of 3D breast surfaces with a low-cost RGBD camera for surgical planning and aesthetic evaluation.

Accounting for 26% of all new cancer cases worldwide, breast cancer remains the most common form of cancer in women. Although early breast cancer has a favourable long-term prognosis, roughly a third of patients suffer from a suboptimal aesthetic outcome despite breast conserving cancer treatment. Clinical-quality 3D modelling of the breast surface therefore assumes an increasingly important role in advancing treatment planning, prediction and evaluation of breast cosmesis. Yet, existing 3D torso scanners are expensive and either infrastructure-heavy or subject to motion artefacts. In this paper we employ a single consumer-grade RGBD camera with an ICP-based registration approach to jointly align all points from a sequence of depth images non-rigidly. Subtle body deformation due to postural sway and respiration is successfully mitigated leading to a higher geometric accuracy through regularised locally affine transformations. We present results from 6 clinical cases where our method compares well with the gold standard and outperforms a previous approach. We show that our method produces better reconstructions qualitatively by visual assessment and quantitatively by consistently obtaining lower landmark error scores and yielding more accurate breast volume estimates.

Systematic review of the impact of breast-conserving surgery on cancer outcomes of multiple ipsilateral breast cancers.

BACKGROUND: The clinical effectiveness of treating ipsilateral multifocal (MF) and multicentric (MC) breast cancers using breast-conserving surgery (BCS) compared with the standard of mastectomy is uncertain. Inconsistencies relate to definitions, incidence, staging and intertumoral heterogeneity. The primary aim of this systematic review was to compare clinical outcomes after BCS versus mastectomy for MF and MC cancers, collectively defined as multiple ipsilateral breast cancers (MIBC). METHODS: Comprehensive electronic searches were undertaken to identify complete papers published in English between May 1988 and July 2015, primarily comparing clinical outcomes of BCS and mastectomy for MIBC. All study designs were included, and studies were appraised critically using the Newcastle-Ottawa Scale. The characteristics and results of identified studies were summarized. RESULTS: Twenty-four retrospective studies were included in the review: 17 comparative studies and seven case series. They included 3537 women with MIBC undergoing BCS; breast cancers were defined as MF in 2677 women, MC in 292, and reported as MIBC in 568. Six studies evaluated MIBC treated by BCS or mastectomy, with locoregional recurrence (LRR) rates of 2-23 per cent after BCS at median follow-up of 59·5 (i.q.r. 56-81) months. BCS and mastectomy showed apparently equivalent rates of LRR (risk ratio 0·94, 95 per cent c.i. 0·65 to 1·36). Thirteen studies compared BCS in women with MIBC versus those with unifocal cancers, reporting LRR rates of 2-40 per cent after BCS at a median follow-up of 64 (i.q.r. 57-73) months. One high-quality study reported 10-year actuarial LRR rates of 5·5 per cent for BCS in 300 women versus 6·5 per cent for mastectomy among 887 women. CONCLUSION: The available studies were mainly of moderate quality, historical and underpowered, with limited follow-up and biased case selection favouring BCS rather than mastectomy for low-risk patients. The evidence was inconclusive, weakening support for the St Gallen consensus and supporting a future randomized trial.

Factors associated with intentional and unintentional non-adherence to adjuvant endocrine therapy following breast cancer.

Adherence to adjuvant endocrine therapy (AET) following breast cancer is known to be suboptimal despite its known efficacy in reducing recurrence and mortality. This study aims to investigate factors associated with non-adherence and inform the development of interventions to support women and promote adherence. A questionnaire survey to measure level of adherence, side effects experienced, beliefs about medicine, support received and socio-demographic details was sent to 292 women 2-4 years post breast cancer diagnosis. Differences between non-adherers and adherers to AET were explored, and factors associated with intentional and unintentional non-adherence are reported. Approximately one quarter of respondents, 46 (22%), were non-adherers, comprising 29 (14%) intentional non-adherers and 17 (8%) unintentional non-adherers. Factors significantly associated with intentional non-adherence were the presence of side effects (p < .03), greater concerns about AET (p < .001) and a lower perceived necessity to take AET (p < .001). Half of the sample (105/211) reported that side effects had a moderate or high impact on their quality of life. Factors associated with unintentional non-adherence were younger age (<65) (p < .001), post-secondary education (p = .046) and paid employment (p = .031). There are distinct differences between intentional non-adherence and unintentional non-adherence. Differentiation between the two types of non-adherence may help tailor support and advice interventions.

Fear of cancer recurrence in oral and oropharyngeal cancer patients: An investigation of the clinical encounter.

Fear of cancer recurrence (FCR) is common among individuals treated for cancer. Explorations of how this fear is expressed within an oncology setting and responded to are currently lacking. The aim was to investigate how head and neck cancer survivors in follow-up consultations express FCR, investigate how a healthcare professional addresses recurrence fears, and examine how survivors experience this interaction. We recorded the follow-up consultations of those participants who have reported FCR as a concern on the Patient Concerns Inventory. We also conducted a follow-up phone interview with the participants. We analysed the transcripts using thematic analysis. Five men and six women were recruited, aged 55-87 (mean age = 64). Follow-up consultation analyses revealed that the consultant used "normalising FCR," "reassurance," and "offer of referral to a counsellor." Interviews revealed themes around how they coped with FCR, relevance of personal history on FCR, and the impact of feeling gratitude towards the consultant on expression of FCR. Analyses indicate that patients may feel reluctant to raise their FCR with their clinician for fear of appearing "ungrateful" or of damaging a relationship that is held in high esteem. Findings indicate the initiation of FCR with patients can be beneficial for patient support.

Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia.

Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible 'knockdown' mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3-4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin-5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder.

Obstacles to reduction in infantile developmental dysplasia of the hip.

PURPOSE: Identification of anatomical structures that block -reduction in developmental dysplasia of the hip (DDH) is -important for the management of this challenging condition. Obstacles to reduction seen on arthrogram are well-known. However, despite the increasing use of MRI in the assessment of adequacy of reduction in DDH, the interpretation of MRI patho-anatomy is ill-defined with a lack of relevant literature to guide clinicians. METHOD: This is a retrospective analysis of the MRI of patients with DDH treated by closed reduction over a five-year period (between 2009 and 2014). Neuromuscular and genetic disorders were excluded. Each MRI was analysed by two orthopaedic surgeons and a paediatric musculoskeletal radiologist to identify the ligamentum teres, pulvinar, transverse acetabular ligament (TAL), capsule, labrum and acetabular roof cartilage hypertrophy. Inter- and intraobserver reliability was calculated. The minimum follow-up was 12 months. RESULTS: A total of 29 patients (38 hips) underwent closed reduction for treatment of DDH. Eight hips showed persistent subluxation on post-operative MRI. Only three of these eight hips showed an abnormality on arthrogram. The pulvinar was frequently interpreted as 'abnormal' on MRI. The main obstacles identified on MRI were the ligamentum teres (15.8%), labrum (13.1%) and acetabular roof cartilage hypertrophy (13.2%). The inter-rater reliability was good for TAL, capsule and pulvinar; moderate for ligamentum teres and labrum; and poor for hypertrophied cartilage. CONCLUSION: The labrum, ligamentum teres and acetabular roof cartilage hypertrophy are the most important structures seen on MRI preventing complete reduction of DDH. Focused interpretation of these structures may assist in the management of DDH.

Does orthopaedic surgery improve quality of life and function in patients with mucopolysaccharidoses?

PURPOSE: Mucopolysaccharidoses (MPS) are a group of rare lysosomal storage disorders associated with involvement of multiple organs along with a generalised skeletal dysplasia. Both haematopoetic stem cell transplant and enzyme replacement therapy have improved the outlook for patients while surgery remains high-risk and there is little information on clinical or functional outcome to justify many of the surgical procedures performed. This paper aims to summarise the orthopaedic surgical procedures in MPS patients for which quality of life (QoL) and functional data are available and to describe additional QoL and functional measurement tools of relevance to the assessment of orthopaedic outcomes in MPS. METHODS: We reviewed the available literature to look for reported outcomes of orthopaedic surgery to lower and upper limbs and the spine. In addition, we describe the general and MPS-specific health measures that might be of relevance to the orthopaedic surgeon. RESULTS: There is some evidence in the literature that orthopaedic surgery may improve QoL and function in some specific aspects of the MPS condition (in relation to genu valgum, carpal tunnel syndrome and trigger digits); however, the literature is sparse and consists of level 4/5 studies only. Further studies of these conditions should include QoL and functional assessment in order to confirm or refute these reports. In other areas (spine and hip), outcomes are judged largely on radiographic appearances with little clinical correlation and short follow-up; however, one long-term study of function following hip dysplasia surgery suggests poor outcomes. Anaesthetic morbidity/mortality is not insignificant in these complex patients with multi-organ involvement. Careful assessment is required, particularly when there is neurological involvement. CONCLUSIONS: Orthopaedic surgeons involved with MPS patients should be encouraged to use and report measures of QoL and function with respect to musculoskeletal manifestations and response to surgery, recognising that such assessments in these complex and challenging patients may require a multidisciplinary approach.