Novel genes and insights in complete asthma remission: A genome-wide association study on clinical and complete asthma remission.

BACKGROUND: Asthma is a chronic respiratory disease without a cure, although there exists spontaneous remission. Genome-wide association (GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission. OBJECTIVE: We performed a GWA study to develop insights in asthma remission. METHODS: Clinical remission (ClinR) was defined by the absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR). A GWA study on both ClinR and ComR was performed in 790 asthmatics with initial doctor diagnosis of asthma and BHR and long-term follow-up. We assessed replication of the 25 top single nucleotide polymorphisms (SNPs) in 2 independent cohorts (total n = 456), followed by expression quantitative loci (eQTL) analyses of the 4 replicated SNPs in lung tissue and epithelium. RESULTS: Of the 790 asthmatics, 178 (23%) had ClinR and 55 ComR (7%) after median follow-up of 15.5 (range 3.3-47.8) years. In ClinR, 1 of the 25 SNPs, rs2740102, replicated in a meta-analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNPs replicated in a meta-analysis of the replication cohorts. The top-hit, rs6581895, almost reached genome-wide significance (P-value 4.68 × 10-7 ) and was an eQTL for FRS2 and CCT in lung tissue. Rs1420101 was a cis-eQTL in lung tissue for IL1RL1 and IL18R1 and a trans-eQTL for IL13. CONCLUSIONS AND CLINICAL RELEVANCE: By defining a strict remission phenotype, we identified 3 SNPs to be associated with complete asthma remission, where 2 SNPs have plausible biological relevance in FRS2, CCT, IL1RL1, IL18R1 and IL13.

Extensive colonization with carbapenemase-producing microorganisms in Romanian burn patients: infectious consequences from the Colectiv fire disaster.

Health care of severe burn patients is highly specialized and may require international patient transfer. Burn patients have an increased risk of developing infections. Patients that have been hospitalized in countries where carbapenemase-producing microorganisms (CPMO) are endemic may develop infections that are difficult to treat. In addition, there is a risk on outbreaks with CPMOs in burn centers. This study underlines that burn patients may extensively be colonized with CPMOs, and it provides best practice recommendations regarding clinical microbiology and infection control. We evaluated CPMO-carriage and wound colonization in a burn patient initially treated in Romania, and transported to the Netherlands. The sequence types and acquired beta-lactamase genes of highly-resistant microorganisms were derived from next generation sequencing data. Next, we searched literature for reports on CPMOs in burn patients. Five different carbapenemase-producing isolates were cultured: two unrelated OXA-48-producing Klebsiella pneumoniae isolates, OXA-23-producing Acinetobacter baumanii, OXA-48-producing Enterobacter cloacae, and NDM-1-producing Providencia stuartii. Also, multi-drug resistant Pseudomonas aeruginosa isolates were detected. Among the sampling sites, there was high variety in CPMOs. We found 46 reports on CPMOs in burn patients. We listed the epidemiology of CPMOs by country of initial treatment, and summarized recommendations for care of these patients based on these reports and our study.

Latrophilin receptors: novel bronchodilator targets in asthma.

BACKGROUND: Asthma affects 300 million people worldwide. In asthma, the major cause of morbidity and mortality is acute airway narrowing, due to airway smooth muscle (ASM) hypercontraction, associated with airway remodelling. However, little is known about the transcriptional differences between healthy and asthmatic ASM cells. OBJECTIVES: To investigate the transcriptional differences between asthmatic and healthy airway smooth muscle cells (ASMC) in culture and investigate the identified targets using in vitro and ex vivo techniques. METHODS: Human asthmatic and healthy ASMC grown in culture were run on Affymetrix_Hugene_1.0_ST microarrays. Identified candidates were confirmed by PCR, and immunohistochemistry. Functional analysis was conducted using in vitro ASMC proliferation, attachment and contraction assays and ex vivo contraction of mouse airways. RESULTS: We suggest a novel role for latrophilin (LPHN) receptors, finding increased expression on ASMC from asthmatics, compared with non-asthmatics in vivo and in vitro, suggesting a role in mediating airway function. A single nucleotide polymorphism in LPHN1 was associated with asthma and with increased LPHN1 expression in lung tissue. When activated, LPHNs regulated ASMC adhesion and proliferation in vitro, and promoted contraction of mouse airways and ASMC. CONCLUSIONS: Given the need for novel inhibitors of airway remodelling and bronchodilators in asthma, the LPHN family may represent promising novel targets for future dual therapeutic intervention.

Individual prediction of long-term outcome in adolescents at ultra-high risk for psychosis: Applying machine learning techniques to brain imaging data.

An important focus of studies of individuals at ultra-high risk (UHR) for psychosis has been to identify biomarkers to predict which individuals will transition to psychosis. However, the majority of individuals will prove to be resilient and go on to experience remission of their symptoms and function well. The aim of this study was to investigate the possibility of using structural MRI measures collected in UHR adolescents at baseline to quantitatively predict their long-term clinical outcome and level of functioning. We included 64 UHR individuals and 62 typically developing adolescents (12-18 years old at recruitment). At six-year follow-up, we determined resilience for 43 UHR individuals. Support Vector Regression analyses were performed to predict long-term functional and clinical outcome from baseline MRI measures on a continuous scale, instead of the more typical binary classification. This led to predictive correlations of baseline MR measures with level of functioning, and negative and disorganization symptoms. The highest correlation (r = 0.42) was found between baseline subcortical volumes and long-term level of functioning. In conclusion, our results show that structural MRI data can be used to quantitatively predict long-term functional and clinical outcome in UHR individuals with medium effect size, suggesting that there may be scope for predicting outcome at the individual level. Moreover, we recommend classifying individual outcome on a continuous scale, enabling the assessment of different functional and clinical scales separately without the need to set a threshold. Hum Brain Mapp 38:704-714, 2017. © 2016 Wiley Periodicals, Inc.

PTTG1IP and MAML3, novel genomewide association study genes for severity of hyperresponsiveness in adult asthma.

BACKGROUND: The severity of bronchial hyperresponsiveness (BHR) is a fundamental feature of asthma. The severity of BHR varies between asthmatics and is associated with lack of asthma control. The mechanisms underlying this trait are still unclear. This study aimed to identify genes associated with BHR severity, using a genomewide association study (GWAS) on the slope of BHR in adult asthmatics. METHODS: We performed a GWAS on BHR severity in adult asthmatics from the Dutch Asthma GWAS cohort (n = 650), adjusting for smoking and inhaled corticosteroid use, and verified results in three other cohorts. Furthermore, we performed eQTL and co-expression analyses in lung tissue. RESULTS: In the discovery cohort, one genomewide significant hit located in phosphodiesterase 4D, cAMP-specif (PDE4D) and 26 SNPs with P-values < 1*10-5 were found. None of our findings replicated in adult and childhood replication cohorts jointly. In adult cohorts separately, rs1344110 in pituitary tumour-transforming 1 interacting protein (PTTG1IP) and rs345983 in Mastermind-like 3 (MAML3) replicated nominally; minor alleles of rs345983 and rs1344110 were associated with less severe BHR and higher lung tissue gene expression. PTTG1IP showed significant co-expression with pituitary tumour-transforming 1, the binding factor of PTTG1lP, and with vimentin and E-cadherin1. MAML3 co-expressed significantly with Mastermind-like 2 (MAML2), both involved in Notch signalling. CONCLUSIONS: PTTG1IP and MAML3 are associated with BHR severity in adult asthma. The relevance of these genes is supported by the eQTL analyses and co-expression of PTTG1lP with vimentin and E-cadherin1, and MAML3 with MAML2.

Indications and Predictors for Reconstructive Surgery After Hand Burns.

PURPOSE: The objective of this study was to analyze the prevalence, indications, and type of reconstructive surgery and predictors of the outcomes of reconstructive surgery after hand burns. METHODS: A retrospective cohort study was conducted that included all patients admitted with acute hand burns in the Dutch burn centers from January 1998 through December 2002. The details of reconstruction including frequency, timing, indication, and techniques were collected over a 10-year follow-up period. RESULTS: Hand burns were seen in 42% (n = 562 of 1,334) of all patients admitted with acute burns. Reconstructive surgery during the 10-year follow-up period was required in 15%. Contractures, especially of the first web space and little finger, were the most frequent indications for reconstructive surgery. Web spaces 1 to 3 and the little finger were the location most frequently operated on. The most frequently performed surgical technique was release of the contractures and the use of a random flap. Eighty percent of the reconstructive surgery patients required more than 1 reconstructive procedure, most often within 2 years of the initial injury. Secondary operations at the same location were required in 12%. In 40% of the patients, the first reconstructive surgery was performed within the first postburn year. Significant independent factors related to the need for reconstructive hand surgery were a larger area of full-thickness burns and surgical treatment of the hand during the acute phase. CONCLUSIONS: Reconstructive surgery was required in 15% of patients who sustained hand burns. The majority of the patients requiring reconstructive surgery of the hand needed 2 or more operations to correct the contractures of the hand. Contractures of the little finger and first web space were the locations most frequently operated on. Patients with more extensive burns and who required hand surgery during the acute phase were more likely to need reconstructive surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Combining genomewide association study and lung eQTL analysis provides evidence for novel genes associated with asthma.

BACKGROUND: Genomewide association studies (GWASs) of asthma have identified single-nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis-eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor's diagnosed) asthma to our GWAS of asthma with BHR. METHODS: A GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts, and lung cis-eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data. RESULTS: A total of 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genomewide significance after meta-analysis. Five of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma-associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature. CONCLUSIONS: Combining GWAS with subsequent lung eQTL analysis revealed disease-associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor's diagnosed) asthma.

Deficiency of FHL2 attenuates airway inflammation in mice and genetic variation associates with human bronchial hyper-responsiveness.

BACKGROUND: Asthma is an inflammatory disease that involves airway hyper-responsiveness and mucus hypersecretion. The LIM-only protein FHL2 is a crucial modulator of multiple signal transduction pathways and functions as a scaffold in specific protein-protein interactions. OBJECTIVE: We sought to investigate the role of FHL2 in airway inflammation. METHODS: Allergic airway inflammation was induced in WT and FHL2-knock out (FHL2-KO) mice with ovalbumin (OVA). Lung tissue, bronchoalveolar lavage fluid (BALF) and draining lymph node cells were analysed for inflammation. FHL2 loss and gain of function studies were performed in lung epithelial cells. RESULTS: FHL2-deficient mice challenged with OVA show significantly reduced airway inflammation as evidenced by reduced infiltration of inflammatory cells including eosinophils, dendritic cells, B cells and T cells. Furthermore, mucus production was decreased in FHL2-KO mice. In BALF, the levels of IL-5, IL-13, eotaxin-1 and eotaxin-2 were significantly lower in FHL2-KO mice. In addition, draining lymph node cells from FHL2-KO mice show reduced levels of IL-5 and IL-13. Consistent with this, OVA-specific serum IgG and IgE levels were reduced in FHL2-KO mice. We also found that phosphorylation of ERK1/2 is markedly attenuated in FHL2-KO lung. Knock-down of FHL2 in human lung epithelial cells resulted in a striking decrease in ERK1/2 phosphorylation and mRNA levels of inflammatory cytokines and MUC5AC, whereas FHL2 overexpression exhibited opposite effects. Finally, the SNP rs4851765 shows an association with the severity of bronchial hyper-responsiveness. CONCLUSION: These results highlight functional involvement of FHL2 in airway inflammation and identify FHL2 as a novel gene associated with asthma severity in human.

Photographic assessment of burn size and depth: reliability and validity.

OBJECTIVE: The aim of this study was to examine the reliability and validity of using photographs of burns to assess both burn size and depth. METHOD: Fifty randomly selected photographs taken on day 0-1 post burn were assessed by seven burn experts and eight referring physicians. Inter-rater reliability in both groups (experts vs. referrers) was calculated. The validity of burn size assessment was calculated using live assessment as the gold standard, and of burn depth using clinical assessment in combination with laser Doppler imaging as the gold standard. The validity of the photographically-assessed indication for surgery was calculated using laser Doppler imaging and actual treatment as the gold standard. Finally, agreement in referral indication was calculated. RESULTS: Using photographs, burn size could be assessed reliably and validly by experts (ICCs of 0.83 and 0.87), but not by referrers (ICCs of 0.68 and 0.78). Photographic assessment of burn depth was neither reliable nor valid, with ICCs respectively of 0.38 and 0.28 for experts and 0.24 and 0.13 for referrers. The indication for surgery could also not be assessed validly. Agreement between assessors regarding referral indication was low. CONCLUSION: Burn size, but not burn depth, can be assessed reliably and validly by experts using photographs of the burn wound. We recommend exploring other forms of telemedicine, like live interactive video, to investigate whether this leads to an improved burn depth assessment where clinical assessment is not possible. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest to declare with regard to the manuscript or its content.

The prevalence and predictors of reconstructive surgery in pediatric burn care.

OBJECTIVE: This study aimed to examine the prevalence and predictors of reconstructive surgery among pediatric burn patients in the Netherlands. METHODS: Pediatric burn patients were identified through the Dutch Burn Repository R3. Eligibility criteria included a burn requiring hospital admission or surgical treatment at one of the Dutch burn centers in 2009-2019. First, patient, burn, and treatment characteristics were summarized using descriptive statistics. Second, time to the first reconstructive surgery was modelled using Kaplan Meier curves. Third, a prediction model was developed using univariate and multivariate logistic regression. The model's performance was assessed using calibration, discrimination, and explained variance. Fourth, internal validation was performed using bootstrapping. RESULTS: Approximately three percent (n = 84) of pediatric patients (n = 3072) required reconstructive surgery between the initial burn-related hospital admission and September 2021. Median time to the first reconstructive surgery was 1.2 (0.7-1.6) years. Most surgeries were performed on the face, arm, neck, hand, or anterior trunk, owing to contractures or hypertrophic scarring. Predictors of reconstruction included the etiology, anatomical site, extent of full-thickness burn, surgical treatment in the acute phase, and length of hospital stay. CONCLUSION: Our study provided an overview of the prevalence and independent predictors of reconstructive surgery in the pediatric burn population.

Outcomes that matter most to burn patients: A national multicentre survey study in the Netherlands.

BACKGROUND: The use of patient-reported outcomes to improve burn care increases. Little is known on burn patients' views on what outcomes are most important, and about preferences regarding online Patient Reported Outcome Measures (PROMs). Therefore, this study assessed what outcomes matter most to patients, and gained insights into patient preferences towards the use of online PROMs. METHODS: Adult patients (≥18 years old), 3-36 months after injury completed a survey measuring importance of outcomes, separately for three time periods: during admission, short-term (<6 months) and long-term (6-24 months) after burn injury. Both open and closed-ended questions were used. Furthermore, preferences regarding the use of patient-reported outcome measures in burn care were queried. RESULTS: A total of 140 patients were included (response rate: 27%). 'Not having pain' and 'good wound healing' were identified as very important outcomes. Also, 'physical functioning at pre-injury level', 'being independent' and 'taking care of yourself' were considered very important outcomes. The top-ten of most important outcomes largely overlapped in all three time periods. Most patients (84%) had no problems with online questionnaires, and many (67%) indicated that it should take up to 15 minutes. Patients' opinions differed widely on the preferred frequency of follow-up. CONCLUSIONS: Not having pain and good wound healing were considered very important during the whole recovery of burns; in addition, physical functioning at pre-injury level, being independent, and taking care of yourself were deemed very important in the short and long-term. These outcomes are recommended to be used in burn care and research, although careful selection of outcomes remains crucial as patients prefer online questionnaires up to 15 minutes.

Development of a value-based healthcare burns core set for adult burn care.

BACKGROUND: Value-based healthcare (VBHC) is increasingly implemented in healthcare worldwide. Transparent measurement of the outcomes most important and relevant to patients is essential in VBHC, which is supported by a core set of most important quality indicators and outcomes. Therefore, the aim of this study was to develop a VBHC-burns core set for adult burn patients. METHODS: A three-round modified national Delphi study, including 44 outcomes and 24 quality indicators, was conducted to reach consensus among Dutch patients, burn care professionals and researchers. Items were rated on a nine-point Likert scale and selected if ≥ 70% in each group considered an item 'important'. Subsequently, instruments quantifying selected outcomes were identified based on a literature review and were chosen in a consensus meeting using recommendations from the Dutch consensus-based standard set and the Dutch Centre of Expertise on Health Disparities. Time assessment points were chosen to reflect the burn care and patient recovery process. Finally, the initial core set was evaluated in practice, leading to the adapted VBHC-burns core set. RESULTS: Twenty-seven patients, 63 burn care professionals and 23 researchers participated. Ten outcomes and four quality indicators were selected in the Delphi study, including the outcomes pain, wound healing, physical activity, self-care, independence, return to work, depression, itching, scar flexibility and return to school. Quality indicators included shared decision-making (SDM), the number of patients receiving aftercare, determination of burn depth, and assessment of active range of motion. After evaluation of its use in clinical practice, the core set included all items except SDM, which are assessed by 9 patient-reported outcome instruments or measured in clinical care. Assessment time points included are at discharge, 2 weeks, 3 months, 12 months after discharge and annually afterwards. CONCLUSION: A VBHC-burns core set was developed, consisting of outcomes and quality indicators that are important to burn patients and burn care professionals. The VBHC-burns core set is now systemically monitored and analysed in Dutch burn care to improve care and patient relevant outcomes. As improving burn care and patient relevant outcomes is important worldwide, the developed VBHC-burns core set could be inspiring for other countries.

Evidence for accelerated colorectal adenoma--carcinoma progression in MUTYH-associated polyposis?

BACKGROUND AND AIM: MUTYH-associated polyposis (MAP) is an autosomal recessive inherited disorder characterised by the development of polyposis in the upper and lower gastrointestinal tract and a high risk of colorectal cancer (CRC). We evaluated the natural history of the disease and the outcome of colorectal surveillance and management. METHODS: A large Western European dataset of biallelic MUTYH mutation carriers comprising 254 patients was used. Detailed information was collected on polyp and cancer development in the colorectum, and the outcome of surveillance and surgery. Survival methods were used to calculate the risk of CRC development. RESULTS: The mean follow-up was 9.8 years. Colorectal polyposis was diagnosed at a mean age of 44.8 years (range: 12-77 years). Most patients had <100 colorectal adenomas at diagnosis. CRC was diagnosed in 147 (58%) of the 254 patients (mean age at diagnosis: 48.5, range: 21-77 years). The cumulative lifetime risk of CRC was 63% at age 60 years. There was no correlation between the number of adenomas and the presence of CRC. The cumulative risk of CRC in patients presenting with polyps was 9% after 5 years of follow-up. Patients presenting with CRC had 11% risk of developing a metachronous CRC at 5 years after surgery. Thirty-seven per cent of patients with MAP with CRC who underwent partial colonic resection needed secondary surgery shortly afterwards. CONCLUSIONS: The high risk of developing CRC under surveillance in patients with MAP may suggest an accelerated carcinogenesis. Surveillance of these patients should therefore include colonoscopy at short intervals, for example, at 1-2-year intervals starting from the age of 18 to 20 years. If surgery for CRC is warranted, a (sub)total colectomy is recommended.

Facilitators & barriers and practices of early mobilization in critically ill burn patients: A survey.

BACKGROUND: Early mobilization (EM) of intensive care (IC) patients is important but complex with facilitators and barriers. Compared to general IC patients, burn IC patients are more hyper-metabolic. They have extensive wounds, lengthy wound dressing changes, and repeated surgeries that may affect possibilities of EM. This study aimed to identify facilitators and barriers of EM in burn IC patients among all disciplines involved. Additionally, we assessed EM practices, i.e. when are which patients considered suitable for EM. METHODS: A survey was sent to 139 professionals involved in EM of burn IC patients (discipline groups: Intensivists, medical doctors, registered nurses, therapists). RESULTS: Response rate was 57 %. The majority found EM very important, yet different definitions were chosen. Perceived barriers mainly concerned patient-level factors, most frequently hemodynamic instability and excessive sedation followed by skin graft surgery, fatigue, and pain management. Most frequent barriers at the provider-level were limited staffing, safety concerns, and conflicting perceptions about the suitability of EM. At the institutional-level, we found no high barriers. Interdisciplinary variation on perceived barriers, when to initiate it, and permitted maximal activity were ascertained. CONCLUSION: Skin grafts and pain management were barriers of EM specific for burn care. Opinions on frequency, dosage and duration of EM varied widely. Improving interdisciplinary communication is key.

Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis.

AIM: Duodenal adenomatosis in familial adenomatous polyposis results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study was to present the results of long-term duodenal surveillance and to evaluate the risk of cancer development. METHOD: Follow up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included the χ(2) test, actuarial method and Kaplan-Meier analysis. RESULTS: Among 304 patients, 261 (86%) had more than one endoscopy. The median follow up was 14 (interquartile range, 9-17) years. The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI, 84-93), and of Spigelman stage IV was 35% (95% CI, 25-45). The Spigelman stage improved in 32 (12%) patients, remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty (7%) patients had duodenal cancer at a median age of 56 (range, 44-82) years. The cumulative cancer incidence was 18% at 75 years of age (95% CI, 8-28) and increased with increasing Spigelman stage at the index endoscopy to 33% in Spigelman stage IV (P < 0.0001). The median overall survival was 6.4 years (95% CI, 1.7 to not estimated): 8 years after a screen-detected cancer vs 0.8 years (95% CI, 0.03-1.7) after a symptomatic cancer (P < 0.0001). The location of the mutation in the APC gene did not influence the risk of developing Spigelman stage IV (P = 0.46) or duodenal cancer (P = 0.83). CONCLUSION: The risk of duodenal cancer in familial adenomatous polyposis is considerable, and regular surveillance and cancer prophylactic surgery result in a significantly improved prognosis.

Is colorectal surveillance indicated in patients with PTEN mutations?

AIM: Patients with germline phosphatase and tensin homologue (PTEN) mutations develop hamartomatous lesions in several organs and are at increased risk of various malignancies. We assessed the lifetime risk of benign and malignant gastrointestinal lesions in patients with a proven PTEN mutation. METHOD: Data on gender, mutation, dates of birth, last contact, and diagnosis, location and type of gastrointestinal lesions were collected from nine countries. The lifetime risk of gastrointestinal lesions was calculated by Kaplan-Meier methods. RESULTS: A total of 156 patients (67 men, 43%) from 101 families with a PTEN mutation were included. Patients were born between 1928 and 2008. Benign gastrointestinal polyps were reported in 49 (31%) patients at a mean age of 38 years (range 18-62 years) and were most often hamartomas. Twenty-two (44%) patients had upper as well as lower gastrointestinal lesions, 14 (29%) had only colonic lesions and 13 (27%) had gastrointestinal lesions at unknown sites. The cumulative risk of developing benign gastrointestinal polyps was 70% at age 60. Four patients (two men) developed colorectal carcinoma at 53, 57, 59 and 62 years, respectively. The cumulative risk of developing colorectal carcinoma was 18% at age 60. Except for one carcinoid in the small intestine, no upper gastrointestinal cancers were observed. CONCLUSION: Benign gastrointestinal lesions are common in PTEN mutation carriers, and a three- to four-fold increased lifetime risk of colorectal cancer compared with the general population may exist. Colorectal screening of patients with germline PTEN mutations is recommended, starting at age 40 years.

The degree of joint range of motion limitations after burn injuries during recovery.

INTRODUCTION: The aim of this study was to determine the degree of ROM limitations of extremities, joints and planes of motion after burns and its prevalence over time. METHOD: The database of a longitudinal multicenter cohort study in the Netherlands (2011-2012) was used. From patients with acute burns involving the neck, shoulder, elbow, wrist, hip, knee and ankle joints that had surgery, ROM of 17 planes of motion was assessed by goniometry at 3, 6 weeks, 3-6-9 and 12 months after burns and at discharge. RESULTS: At 12 months after injury, 12 out of 17 planes of motion demonstrated persistent joint limitations. The five unlimited planes of motion were all of the lower extremity. The most severely limited joints at 12 months were the neck, ankle, wrist and shoulder. The lower extremity was more severely limited in the early phase of recovery whereas at 12 months the upper extremity was more severely limited. CONCLUSION: The degree of ROM limitations and prevalence varied over time between extremities, joints and planes of motion. This study showed which joints and planes of motion should be watched specifically concerning the development of scar contracture.

The development of burn scar contractures and impact on joint function, disability and quality of life in low- and middle-income countries: A prospective cohort study with one-year follow-up.

OBJECTIVE: The aim of this study was to assess the development of burn scar contractures and their impact on joint function, disability and quality of life in a low-income country. METHODS: Patients with severe burns were eligible. Passive range of motion (ROM) was assessed using lateral goniometry. To assess the development of contractures, the measured ROM was compared to the normal ROM. To determine joint function, the normal ROM was compared to the functional ROM. In addition, disability and quality of life (QoL) were assessed. Assessments were from admission up to 12 months after injury. RESULTS: Thirty-six patients were enrolled, with a total of 124 affected joints. The follow-up rate was 83%. Limited ROM compared to normal ROM values was observed in 26/104 joints (25%) at 12 months. Limited functional ROM was observed in 55/115 joints (48%) at discharge and decreased to 22/98 joints (22%) at 12 months. Patients who had a contracture at 12 months reported more disability and lower QoL, compared to patients without a contracture (median disability 0.28 versus 0.17 (p = 0.01); QoL median 0.60 versus 0.76 (p = 0.001)). Significant predictors of developing joint contractures were patient delay and the percentage of TBSA deep burns. CONCLUSION: The prevalence of burn scar contractures was high in a low-income country. The joints with burn scar contracture were frequently limited in function. Patients who developed a contracture reported significantly more disability and lower QoL. To limit the development of burn scar contractures, timely access to safe burn care should be improved in low-income countries.

Acute burn care in resource-limited settings: A cohort study on treatment and outcomes in a rural regional referral hospital in Tanzania.

BACKGROUND: Only a few papers are published on the safety and effectiveness of acute burn care in low-income countries. A cohort study was therefore carried out to determine such outcomes. METHODS: The study was conducted in a rural Tanzanian hospital in 2017-2018. All patients admitted with burns were eligible. Complications were scored during admission as an indication for safety. Survivors of severe burn injuries were evaluated for time of reepithelialization, graft take, disability (WHODAS2.0) and quality of life (EQ5D-3L) up to 3 months post-injury, as an indication of effectiveness. RESULTS: Patients presented on average at 5 days after injury (SD 11, median 1, IQR 0-4). Three patients died at admission. The remaining 79 were included in the cohort. Their median age was 3 years (IQR 2-9, range 0.5-49), mean TBSA burned 12% (SD10%) and mortality rate 11.4%. No surgery-related mortality or life-threatening complications were observed. Skin grafting was performed on 29 patients at a delayed stage (median 23 days, IQR 15-47). Complications of skin grafts included partial (25% of procedures) and complete graft necrosis (8% of procedures). The mean time to reepithelialization was 52 (SD 42) days after admission. Disability and quality of life improved from admission to 3 months after injury (p<0.001, p<0.001, respectively). CONCLUSION: In this resource-limited setting patients presented after a delay and with multiple complications. The mortality during the first two weeks after admission was high. Surgery was found to be safe and effective. A significant improvement in disability and quality of life was observed.

Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients.

BACKGROUND: The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients. METHODS: Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management, and outcome were analysed retrospectively. Progression-free survival (PFS) rates and final outcome were compared for surgical vs non-surgical treatment, for intra-abdominal and extra-abdominal desmoids separately. Also, pharmacological treatment was evaluated for all desmoids. RESULTS: Median follow-up was 8 years. For intra-abdominal desmoids (n=62), PFS rates at 10 years of follow-up were comparable after surgical and non-surgical treatment (33% and 49%, respectively, P=0.163). None of these desmoids could be removed entirely. Eventually, one fifth died from desmoid disease. Most extra-abdominal and abdominal wall desmoids were treated surgically with a PFS rate of 63% and no deaths from desmoid disease. Comparison between NSAID and anti-estrogen treatment showed comparable outcomes. Four of the 10 patients who received chemotherapy had stabilisation of tumour growth, all after doxorubicin combination therapy. CONCLUSION: For intra-abdominal desmoids, a conservative approach and surgery showed comparable outcomes. For extra-abdominal and abdominal wall desmoids, surgery seemed appropriate. Different pharmacological therapies showed comparable outcomes. If chemotherapy was given for progressively growing intra-abdominal desmoids, most favourable outcomes occurred after combinations including doxorubicin.