Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

Moment-generating function zeros in the study of phase transitions.

Partition function zeros play a central role in the study of phase transitions. Recently, energy probability distribution (EPD) zeros were proposed as an alternative approach that solves some of the implementation issues present in the Fisher zeros method by allowing drastic reduction of the polynomial. Here, a formulation based on the EPD zeros that can reduce even more the polynomial degree while maintaining its accuracy is presented. This method has shown to be computationally cheaper than the EPD zeros, allowing the study of systems by using partition function zeros that would be unfeasible otherwise. In addition, the method can be easily extended to study phase transitions in external fields while maintaining all of its improvements.

Effects of magnetic monopoles charge on the cracking reversal processes in artificial square ices.

In this paper we perform nanofabrication of square artificial spin ices with different lattice parameters, in order to investigate the roles of vertex excitation on the features of the system. In particular, the character of magnetic charge distribution asymmetry on the vertices are observed under magnetic hysteresis loop experiments. We then compare our results with simulation using an emergent Hamiltonian containing objects such as magnetic monopoles and dipoles in the vertices of the array (instead of the usual Hamiltonian based on the dipolar interactions among the magnetic nanoislands). All possible interactions between these objects are considered (monopole-monopole, monopole-dipole and dipole-dipole). Using realistic parameters we observe very good match between experiments and theory, which allow us to better understand the system dynamics in function of monopole charge intensity.

Citronellal prevents endothelial dysfunction and atherosclerosis in rats.

BACKGROUND: Atherosclerosis is a chronical inflammatory disease in arterial walls, which is involved in oxidative stress and endothelial dysfunction. Aromatherapy is one of the complementary therapies that use essential oils as the major therapeutic agents to treat several diseases. Citronellal (CT) is a monoterpene predominantly formed by the secondary metabolism of plants, producing antithrombotic, antiplatelet, and antihypertensive activities. AIM: The aim of the present study is to explore whether aromatherapy with CT improves endothelial function to prevent the formation of atherosclerotic plaque in vivo. METHODS: An AS model in carotid artery was induced by balloon injury and vitamin D3 injection in rats fed with a high-fat diet. The size of the carotid atherosclerotic plaque was determined by ultrasound, oil red, and hematoxylin-eosin staining. Endothelial function was assessed by measuring acetylcholine-induced vessel relaxation in an organ chamber. RESULTS: Administrations of CT (50, 100, and 150 mg/kg) as well as lovastatin dramatically reduced the size of carotid atherosclerotic plaque in rats in a dose-dependent manner, compared with atherosclerotic rats fed with a high-fat diet plus balloon injury and vitamin D3. Mechanically, CT improved endothelial dysfunction, increased cell migration, and suppressed oxidative stress and inflammation in vascular endothelium in rats feeding on the high-fat diet plus balloon injury. Further, CT downregulated the protein levels of sodium-hydrogen exchanger 1 in rats with atherosclerosis. CONCLUSION: CT improves endothelial dysfunction and prevents the growth of atherosclerosis in rats by reducing oxidative stress. Clinically, CT is potentially considered as a medicine to treat patients with atherosclerosis.

Descriptive analysis of rabies in wild animals in the state of Sergipe, Brazil / Análise descritiva da raiva em animais silvestres no estado de Sergipe, Brasil

The wild cycle of rabies constitutes a serious challenge to epidemiological surveillance for disease control in domestic, companion or production animals, and in humans. The understanding of rabies virus circulation in the natural environment is increasingly important due to the constancy of natural reservoirs of the disease and the presence of potential vectors of the infection to humans and domestic animals. Aiming to evaluate the occurrence of rabies in the State of Sergipe a total of 935 hematophagous bats (Desmodus rotundus), 46 wild dogs (Cerdocyon thous) and 24 primates (Callithrix spp.) were analyzed from 1987 to 2014, of which 1 bat, 17 crab-eating foxes and no primates were positive. Due to the lack of positive results in hematophagous bats, the main vector of herbivorous rabies, more studies are needed to monitor cases, because from an epidemiological point of view, Sergipe is endemic for herbivorous rabies. Epidemiological surveillance of rabies virus in wild animals is primordial for the success of disease control programs in herds of domestic animals and humans.(AU)

O ciclo silvestre da raiva constitui um sério desafio para a vigilância epidemiológica no controle da doença nos animais domésticos, de companhia ou de produção, e nos seres humanos. O entendimento sobre a circulação do vírus rábico no ambiente natural é cada vez mais importante, em razão da constância de reservatórios naturais da doença e da presença de vetores potenciais da infecção aos humanos e aos animais domésticos. Com o objetivo de avaliar a ocorrência da raiva no estado de Sergipe, foram analisados 935 morcegos hematófagos (Desmodus rotundus), 46 cachorros-do-mato (Cerdocyon thous) e 24 primatas (Callithrix spp.) no período de 1987 a 2014, dos quais resultaram positivos um morcego, 17 cachorros-do-mato e nenhum primata. Em que pese a contundente falta de resultados positivos em morcegos hematófagos, principal vetor da raiva dos herbívoros, mais estudos são necessários no monitoramento dos casos, pois o estado, do ponto de vista epidemiológico, é endêmico para a raiva dos herbívoros. A vigilância epidemiológica do vírus da raiva nos animais silvestres é primordial para o sucesso dos programas de controle da doença em rebanhos de animais domésticos e em seres humanos.(AU)

Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group.

BACKGROUND: Hand-foot syndrome (HFS) is a common side-effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients. This study compares the incidence of HFS between S-1 and capecitabine as first-line treatment in Western metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Patients with previously untreated mCRC and planned treatment with fluoropyrimidine monochemotherapy were randomized 1 : 1 to receive either capecitabine (1250 mg/m2 orally for patients <70 years; 1000 mg/m2 for patients ≥70 years, twice daily on days 1-14) or S-1 (30 mg/m2 orally twice daily on days 1-14) in 3-weekly cycles, with bevacizumab optional in both groups. The primary endpoint was the incidence of any grade HFS, as assessed by both physicians and patients (diaries). Secondary endpoints included grade 3 HFS, other toxicities, relative dose intensity, progression-free survival, response rate and overall survival. RESULTS: A total of 161 patients were randomized in 27 centres. The incidence of any grade HFS as assessed by physicians was 73% in the capecitabine group (n = 80) and 45% in the S-1 group (n = 80) [odds ratio (95% confidence interval) 0.31 (0.16-0.60), P = 0.0005]. The incidence of grade 3 HFS was 21% and 4% (P = 0.003), respectively. Patient-assessed any grade HFS was 84% and 58%, respectively (P = 0.004). Grade 3 anorexia was more common in the S-1 group (3% versus 13%, P = 0.03). Median relative dose intensity was 88% in the capecitabine group and 95% in the S-1 group (P = 0.026). There were no statistically significant differences in median progression-free survival, response rate and overall survival rates. CONCLUSION: Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01918852.

Cost-effectiveness of capecitabine and bevacizumab maintenance treatment after first-line induction treatment in metastatic colorectal cancer.

AIM: Capecitabine and bevacizumab (CAP-B) maintenance therapy has shown to be more effective compared with observation in metastatic colorectal cancer patients achieving stable disease or better after six cycles of first-line capecitabine, oxaliplatin, bevacizumab treatment in terms of progression-free survival. We evaluated the cost-effectiveness of CAP-B maintenance treatment. METHODS: Decision analysis with Markov modelling to evaluate the cost-effectiveness of CAP-B maintenance compared with observation was performed based on CAIRO3 study results (n = 558). An additional analysis was performed in patients with complete or partial response. The primary outcomes were the incremental cost-effectiveness ratio (ICER) defined as the additional cost per life year (LY) and quality-adjusted life years (QALY) gained, calculated from EQ-5D questionnaires and literature and LYs gained. Univariable sensitivity analysis was performed to assess the influence of input parameters on the ICER, and a probabilistic sensitivity analysis represents uncertainty in model parameters. RESULTS: CAP-B maintenance compared with observation resulted in 0.21 QALYs (0.18LYs) gained at a mean cost increase of €36,845, yielding an ICER of €175,452 per QALY (€204,694 per LY). Varying the difference in health-related quality of life between CAP-B maintenance and observation influenced the ICER most. For patients achieving complete or partial response on capecitabine, oxaliplatin, bevacizumab induction treatment, an ICER of €149,300 per QALY was calculated. CONCLUSION: CAP-B maintenance results in improved health outcomes measured in QALYs and LYs compared with observation, but also in a relevant increase in costs. Despite the fact that there is no consensus on cost-effectiveness thresholds in cancer treatment, CAP-B maintenance may not be considered cost-effective.

The prognostic value of WHO performance status in relation to quality of life in advanced colorectal cancer patients.

INTRODUCTION: Performance status (PS) is an established prognostic factor in patients with advanced cancer and is usually scored by the treating physician. The EORTC QLQ-C30 questionnaire as reported by cancer patients is a validated tool to assess quality of life (QoL). Subjectivity plays a role in both assessments, and data on a direct comparison are scarce. METHODS: We compared the prognostic value for overall survival (OS) of the WHO PS to the baseline physical function scale of the EORTC QLQ-C30 (QLQ-C30 PF) in a prospective randomised phase 3 trial in advanced colorectal cancer (ACC), the CAIRO study. Patients were divided into two groups based on the baseline QLQ-C30 PF. QLQ-C30 PF was considered 'good' if the score was more than 66.7% and 'poor' if 66.7% or less. Results were validated in a subsequent phase 3 study in ACC, the CAIRO2 study. RESULTS: The median OS for patients with a 'good' QLQ-C30 PF and a 'poor' PF in patients with WHO PS 0 was 20.3 months (n = 300) and 10.4 months (n = 44), in patients with WHO PS 1 16.8 months (n = 125) and 10.1 months (n = 63), and in patients with WHO PS 2 16.2 months (n = 11) and 9.9 months (n = 12), respectively. In a Cox regression model which included other prognostic factors, 'good' versus 'poor' QLQ-C30 PF was significantly prognostic for OS (0.57 95% confidence interval: 0.46-0.72), but not WHO PS. These results were confirmed in the CAIRO2 study. CONCLUSIONS: We demonstrate in ACC patients that PF, as assessed by patients using the EORTC QLQ-C30, is superior in terms of prognostic value to WHO PS as scored by physicians. Our data support to include the results of baseline EORTC QLQ-C30 PF instead of WHO PS as a stratification parameter in oncology trials.

Emergence and mobility of monopoles in a unidirectional arrangement of magnetic nanoislands.

Magnetricity, the magnetic equivalent of electricity, was recently verified experimentally for the first time. Indeed, like the stream of electric charges that produces electric current, emergent magnetic monopoles have been observed to roam freely in geometrically frustrated magnets known as spin ice. However, such phenomena demand extreme physical conditions, say, a single spin ice crystal has to be cooled to very low temperature, around 0.36 K. Candidates to overcome this difficulty are their artificial analogues, the so-called artificial spin ices. Here, we demonstrate that a specific unidirectional arrangement of nanoislands yields a peculiar system where magnetic monopoles emerge and are constrained to move along aligned dipoles, providing an ordered flow of magnetic charges at room temperature.

Magnetic anisotropy of elongated thin ferromagnetic nano-islands for artificial spin ice arrays.

The energetics of thin elongated ferromagnetic nano-islands is considered for some different shapes, aspect ratios and applied magnetic field directions. These nano-island particles are important for artificial spin ice materials. For low temperature, the magnetic internal energy of an individual particle is evaluated numerically as a function of the direction of a particle's net magnetization. This leads to estimations of effective anisotropy constants for (1) the easy axis along the particle's long direction, and (2) the hard axis along the particle's thin direction. A spin relaxation algorithm together with fast Fourier transform for the demagnetization field is used to solve the micromagnetics problem for a thin system. The magnetic hysteresis is also found. The results indicate some possibilities for controlling the equilibrium and dynamics in spin ice materials by using different island geometries.

The effect of prophylactic calcium and magnesium infusions on the incidence of neurotoxicity and clinical outcome of oxaliplatin-based systemic treatment in advanced colorectal cancer patients.

BACKGROUND: Peripheral sensory neurotoxicity is a frequent and potentially debilitating side effect of oxaliplatin treatment. Calcium and magnesium (Ca/Mg) infusions are frequently used to prevent this toxicity. However, concerns about a negative impact of Ca/Mg infusions on outcome have been raised. We retrospectively assessed the effect of Ca/Mg infusions on the incidence of neurotoxicity and on clinical outcome in advanced colorectal cancer (ACC) patients treated in the phase III CAIRO2 study. MATERIALS AND METHODS: Seven hundred and fifty five previously untreated ACC patients were randomised between treatment with capecitabine, oxaliplatin and bevacizumab or the same combination with the addition of cetuximab. Patients were retrospectively divided into two groups: patients in the Ca/Mg(+) group received Ca/Mg at least during their first treatment cycle, and patients in the Ca/Mg(-) group did not. RESULTS: Seven hundred and thirty two patients were evaluable for this analysis. The Ca/Mg(+) group consisted of 551 patients, the Ca/Mg(-) group consisted of 181 patients. The incidence of all grade neurotoxicity in the Ca/Mg(+) group and the Ca/Mg(-) group was 85% and 92%, respectively (p = 0.02), and the incidence of grade ≥ 2 neurotoxicity was 40% and 45%, respectively (p = 0.22). The median PFS in the Ca/Mg(+) versus Ca/Mg(-) group was 10.1 versus 10.7 months (p = 0.92), the median OS was 19.8 versus 20.7 months (p = 0.10), and the response rate was 43.1% versus 50% (p = 0.11), respectively. CONCLUSIONS: In this largest retrospective analysis to date we observed that Ca/Mg infusions significantly reduced all grade oxaliplatin-related neurotoxicity. Ca/Mg infusions did not affect the clinical efficacy of treatment.

Clinicopathological features and outcome in advanced colorectal cancer patients with synchronous vs metachronous metastases.

BACKGROUND: Synchronous metastases of colorectal cancer (CRC) are considered to be of worse prognostic value compared with metachronous metastases, but only few and conflicting data have been reported on this issue. METHODS: We retrospectively investigated patient demographics, primary tumour characteristics and overall survival (OS) in 550 advanced CRC patients with metachronous vs synchronous metastases, who participated in the phase III CAIRO study. For this purpose only patients with a prior resection of the primary tumour were considered. RESULTS: The clinical and pathological characteristics associated with poor prognosis that we observed more often in patients with synchronous metastases (n=280) concerned an abnormal serum lactate dehydrogenase (LDH) concentration (P=0.01), a worse WHO performance status (P=0.02), primary tumour localisation in the colon (P=0.002) and a higher T stage (P=0.0006). No significant difference in median OS was observed between patients with synchronous metastases and metachronous metastases (17.6 vs 18.5 months, respectively, P=0.24). CONCLUSION: Despite unfavourable clinicopathological features in patients with synchronous metastases with a resected primary tumour compared to patients with metachronous metastases, no difference in the median OS was observed. Possible explanations include a (partial) chemoresistance in patients with metachronous disease because of previous adjuvant treatment, whereas differences between the two groups in screening procedures resulting in a lead time bias to diagnosis or in prognostic molecular markers remain speculative.

Management of isolated nonresectable liver metastases in colorectal cancer patients: a case-control study of isolated hepatic perfusion with melphalan versus systemic chemotherapy.

BACKGROUND: To compare the median overall survival of patients with isolated nonresectable liver metastases in comparable groups of patients treated with either isolated hepatic perfusion (IHP) with melphalan or systemic chemotherapy. PATIENTS AND METHODS: Colorectal cancer patients with isolated liver metastases, who underwent IHP, were included in this study. The control group consisted of a subgroup of colorectal cancer patients with liver metastases only, who were enrolled in the randomized CApecitabine, IRinotecan, Oxaliplatin (CAIRO) phase III study. RESULTS: Ninety-nine patients were treated with IHP, and 111 patients were included in the control group. All patient characteristics were comparable except for age. Median follow-up was 78.1 months for IHP versus 54.7 months in the control group. Median overall survival was 25.0 [95% confidence interval (CI) 19.4-30.6] months for IHP and 21.7 (95% CI 19.6-23.8) months for systemic treatment and did not differ significantly (P = 0.29). Treatment-related mortality was 2% for the systemic treatment and 6% for IHP (P = 0.11). CONCLUSION: Compared with a patient group with comparable characteristics treated with systemic chemotherapy, IHP does not provide a benefit in overall survival in patients with isolated nonresectable colorectal liver metastases. Currently, the use of IHP cannot be advocated outside the scope of clinical studies.

Phase transition in the two-dimensional dipolar planar rotator model.

In this work we have used extensive Monte Carlo simulations and finite size scaling theory to study the phase transition in the dipolar planar rotator model (dPRM), also known as dipolar XY model. The true long-range character of the dipolar interactions was taken into account by using the Ewald summation technique. Our results for the critical exponents do not fit those from known universality classes. We observed that the specific heat is apparently non-divergent and the critical exponents are ν = 1.277(2), ß = 0.2065(4) and γ = 2.218(5). The critical temperature was found to be T(c) = 1.201(1). Our results are clearly distinct from those of a recent renormalization group study from Maier and Schwabl (2004 Phys. Rev. B 70 134430) and agrees with the results from a previous study of the anisotropic Heisenberg model with dipolar interactions in a bilayer system using a cut-off in the dipolar interactions (Mól and Costa 2009 Phys. Rev. B 79 054404).

A prospective monitoring of fatal serious adverse events (SAEs) in a Dutch Colorectal Cancer Group (DCCG) phase III trial (CAIRO) in patients with advanced colorectal cancer.

BACKGROUND: Early and correct assessment of treatment-related mortality is highly important in clinical cancer trials. However, no data are available on the quality of safety monitoring. PATIENTS AND METHODS: An on-site review was carried out by the study coordinators of the individual charts of all patients participating in the Capecitabine-Irinotecan-Oxaliplatin (CAIRO) study who had died within 30 days of the last administration of study drugs when death was accompanied by any other event than disease progression. The relationship between treatment and death was categorized as unrelated, remote, possible, or probable and submitted to an independent data monitoring committee (IDMC). These results were then compared with the initial assessment of the local investigator. RESULTS: Forty of 820 patients qualified for review. The relationship between cause of death and study drugs was changed in 26 patients (65%). A major protocol violation (MPV) was identified in 12 of 14 patients with a probable relationship between cause of death and study treatment. CONCLUSIONS: There was little agreement between the relation as assessed by the local investigator compared with the IDMC. A quality control improves the assessment of safety results and the observed MPVs underscore the importance of educating medical staff and patients.

Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation.

Chemotherapy plus bevacizumab is currently considered as the standard 1st line treatment of advanced colorectal cancer (ACC). Whereas GI perforation is a known side effect of bevacizumab, the development of GI ulcers has not been reported. We identified 18 patients with ACC who participated in a phase III multicentre trial which included chemotherapy and bevacizumab, who developed a GI ulcer (n = 6), perforation (n = 8) or both (n = 4). The risk of developing a symptomatic GI ulcer or perforation was 1.3% and 1.6%, respectively. Central review of the histology specimens showed ulceration and/or granulation tissue with neovascularisation. The majority (89%) of events developed early during treatment. Given these observations, as well as the relationship between VEGF and mucosal injury healing, we suggest that GI ulcers may occur as a side effect of treatment with bevacizumab and may herald perforation.

A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity.

BACKGROUND: Targeting the vascular endothelial growth factor or the epidermal growth factor receptor (EGFR) has shown efficacy in advanced colorectal cancer (ACC), but no data are available on the combination of these strategies with chemotherapy in the first-line treatment. The CAIRO2 study evaluates the effect of adding cetuximab, a chimeric mAb against EGFR, to capecitabine, oxaliplatin and bevacizumab in the first-line treatment of ACC. PATIENTS AND METHODS: In all, 755 patients were randomly assigned between treatment with capecitabine, oxaliplatin and bevacizumab with or without cetuximab. The primary end point is progression-free survival. We here present the toxicity results in the first 400 patients that entered the study. RESULTS: The incidence of overall grade 3-4 toxicity was significantly higher in arm B compared with arm A (81% versus 72%, P = 0.03). This difference is fully attributed to cetuximab-related skin toxicity. The addition of cetuximab did not result in an increase of gastrointestinal toxicity or treatment-related mortality. CONCLUSIONS: The addition of cetuximab to capecitabine, oxaliplatin and bevacizumab in the first-line treatment of ACC appears to be safe and feasible. No excessive or unexpected toxicity in the cetuximab-containing treatment arm was observed.

Interlaboratory comparison of methods To quantify microsclerotia of verticillium dahliae in soil

In a comparison of different methods for estimating Verticillium dahliae in soil, 14 soil samples were analyzed in a blinded fashion by 13 research groups in seven countries, using their preferred methods. One group analyzed only four samples. Twelve soil samples were naturally infested, and two had known numbers of microsclerotia of V. dahliae added to them. In addition, a control was included to determine whether transport had an effect on the results. Results differed considerably among the research groups. There was a 118-fold difference between the groups with the lowest and highest mean estimates. Results of the other groups were evenly distributed between these extremes. In general, methods based on plating dry soil samples gave higher numbers of V. dahliae than did plating of an aqueous soil suspension. Recovery of V. dahliae from samples with added microsclerotia varied from 0 to 59%. Most of the variability within each analysis was at the petri dish level. The results indicate the necessity to check the performance of detection assays regularly by comparing recoveries with other laboratories, using a common set of soil samples. We conclude that wet plating assays are less accurate than dry plating assays.

Late sequelae of neonatal septic arthritis of the shoulder.

We reviewed eight children (ten shoulders) who had suffered neonatal sepsis, after a mean follow-up of 14 years (11 to 15). The delay between the onset of symptoms and diagnosis was one day in five patients, two days in three and seven days in one. All ten shoulders were treated by aspiration, followed by arthrotomy in two. At follow-up, five of the ten shoulders had a full range of movement and the others had minimal restriction of external rotation. Shortening of 10 cm was present in one patient, while two with bilateral involvement had disproportionally short humeri. Early diagnosis and treatment favour the outcome in septic arthritis of the shoulder. With late diagnosis, deformation of the humeral head and shortening of the humerus cause marked cosmetic abnormality but negligible functional loss.

[One hundred years of orthopedics in the Netherlands. VI. Surgical treatment of rheumatoid arthritis]. / Honderd jaar orthopedie in Nederland. VI. Reumachirurgie.

The prevalence of rheumatoid arthritis is about 1%. Loss of independence during daily activities is closely related to the multiple joint involvement of these patients. Also, chronic systemic autoimmune diseases and the extra-articular lesions cause considerable comorbidity. Goal of medical treatment is to reduce disease activity and local joint destruction. The surgical treatment consists of joint protective surgery and joint reconstructive surgery. The former procedure inhibits rapid progression of joint destruction by eradicating the bulk of synovial tissue. The latter procedure compensates for functional loss of an extremity by arthroplasties (both endoprostheses and arthrodeses) to increase the patient's independence. The perfect long-lasting functional prosthesis is available for some joints (hip and knee), but still in development for other joints (e.g. finger joints). In case of surgical reconstruction, a plan for possible complications (e.g. loosening) and their functional implications for the specific patient, should be part of the surgical indication policy. The outcome after a surgical procedure is closely related to preoperative patient factors (e.g. joint destruction) and the surgical expertise. Co-ordination of the treatment plan has to be done by the rheumatologist in close conjunction with the orthopedic/rheuma surgeon.