Complejo Hospitalario Universitario de Toledo

BACKGROUND: Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. METHODS: We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. RESULTS: Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3-30.2%] in kidney transplant and 25.0% (95% CI 20.2-30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59-1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation <1 year before presentation (HR adjusted for sex, age and frailty 0.20, 95% CI 0.07-0.56, P < 0.01). CONCLUSIONS: The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

OBJECTIVE: To determine the effectiveness of early physiotherapy in reducing the risk of secondary lymphoedema after surgery for breast cancer. DESIGN: Randomised, single blinded, clinical trial. SETTING: University hospital in Alcalá de Henares, Madrid, Spain. PARTICIPANTS: 120 women who had breast surgery involving dissection of axillary lymph nodes between May 2005 and June 2007. INTERVENTION: The early physiotherapy group was treated by a physiotherapist with a physiotherapy programme including manual lymph drainage, massage of scar tissue, and progressive active and action assisted shoulder exercises. This group also received an educational strategy. The control group received the educational strategy only. MAIN OUTCOME MEASURE: Incidence of clinically significant secondary lymphoedema (>2 cm increase in arm circumference measured at two adjacent points compared with the non-affected arm). RESULTS: 116 women completed the one year follow-up. Of these, 18 developed secondary lymphoedema (16%): 14 in the control group (25%) and four in the intervention group (7%). The difference was significant (P=0.01); risk ratio 0.28 (95% confidence interval 0.10 to 0.79). A survival analysis showed a significant difference, with secondary lymphoedema being diagnosed four times earlier in the control group than in the intervention group (intervention/control, hazard ratio 0.26, 95% confidence interval 0.09 to 0.79). CONCLUSION: Early physiotherapy could be an effective intervention in the prevention of secondary lymphoedema in women for at least one year after surgery for breast cancer involving dissection of axillary lymph nodes. TRIAL REGISTRATION: Current controlled trials ISRCTN95870846.

Macrophage activation comprises a continuum of functional states critically determined by cytokine microenvironment. Activated macrophages have been functionally grouped according to their response to pro-Th1/proinflammatory stimuli [lipopolysaccharide, IFNgamma, granulocyte macrophage colony-stimulating factor (GM-CSF); M1] or pro-Th2/anti-inflammatory stimuli [interleukin (IL)-4, IL-10, M-CSF; M2]. We report that folate receptor beta (FRbeta), encoded by the FOLR2 gene, is a marker for macrophages generated in the presence of M-CSF (M2), but not GM-CSF (M1), and whose expression correlates with increased folate uptake ability. The acquisition of folate uptake ability by macrophages is promoted by M-CSF, maintained by IL-4, prevented by GM-CSF, and reduced by IFNgamma, indicating a link between FRbeta expression and M2 polarization. In agreement with in vitro data, FRbeta expression is detected in tumor-associated macrophages (TAM), which exhibit an M2-like functional profile and exert potent immunosuppressive functions within the tumor environment. FRbeta is expressed, and mediates folate uptake, by CD163(+) CD68(+) CD14(+) IL-10-producing TAM, and its expression is induced by tumor-derived ascitic fluid and conditioned medium from fibroblasts and tumor cell lines in an M-CSF-dependent manner. These results establish FRbeta as a marker for M2 regulatory macrophage polarization and indicate that folate conjugates of therapeutic drugs are a potential immunotherapy tool to target TAM.

BACKGROUND: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer. METHODS: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case-control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase. RESULTS: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24-1.48), radiotherapy (OR 1.35, 95% CI 1.16-1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73-3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03-1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01-1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy. INTERPRETATION: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery.

MAIN DISORDERS OF IRON METABOLISM: Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron deficiency anaemia. In chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, resulting in hypoferraemia and iron restricted erythropoiesis, despite normal iron stores (functional iron deficiency), and finally anaemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD+ID). In contrast, low hepcidin expression may lead to hereditary haemochromatosis (HH type I, mutations of the HFE gene) and type II (mutations of the hemojuvelin and hepcidin genes). Mutations of transferrin receptor 2 lead to HH type III, whereas those of the ferroportin gene lead to HH type IV. All these syndromes are characterised by iron overload. As transferrin becomes saturated in iron overload states, non-transferrin bound iron appears. Part of this iron is highly reactive (labile plasma iron), inducing free radical formation. Free radicals are responsible for the parenchymal cell injury associated with iron overload syndromes. ROLE OF LABORATORY TESTING IN DIAGNOSIS: In iron deficiency status, laboratory tests may provide evidence of iron depletion in the body or reflect iron deficient red cell production. Increased transferrin saturation and/or ferritin levels are the main cues for further investigation of iron overload. The appropriate combination of different laboratory tests with an integrated algorithm will help to establish a correct diagnosis of iron overload, iron deficiency and anaemia. REVIEW OF TREATMENT OPTIONS: Indications, advantages and side effects of the different options for treating iron overload (phlebotomy and iron chelators) and iron deficiency (oral or intravenous iron formulations) will be discussed.

BACKGROUND: Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized. OBJECTIVE: To describe and classify cutaneous reactions after SARS-CoV-2 vaccination. METHODS: A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification. RESULTS: From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment. CONCLUSIONS: Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.

Abstract Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease ( HLA-DQA1 p = 4 × 10 −17 ), arthritis ( GDF5 p = 4 × 10 −13 ), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.

IRON FUNCTIONS: Iron is an essential micronutrient, as it is required for satisfactory erythropoietic function, oxidative metabolism and cellular immune response. IRON PHYSIOLOGY: Absorption of dietary iron (1-2 mg/day) is tightly regulated and just balanced against iron loss because there are no active iron excretory mechanisms. Dietary iron is found in haem (10%) and non-haem (ionic, 90%) forms, and their absorption occurs at the apical surface of duodenal enterocytes via different mechanisms. Iron is exported by ferroportin 1 (the only putative iron exporter) across the basolateral membrane of the enterocyte into the circulation (absorbed iron), where it binds to transferrin and is transported to sites of use and storage. Transferrin-bound iron enters target cells-mainly erythroid cells, but also immune and hepatic cells-via receptor-mediated endocytosis. Senescent erythrocytes are phagocytosed by reticuloendothelial system macrophages, haem is metabolised by haem oxygenase, and the released iron is stored as ferritin. Iron will be later exported from macrophages to transferrin. This internal turnover of iron is essential to meet the requirements of erythropoiesis (20-30 mg/day). As transferrin becomes saturated in iron-overload states, excess iron is transported to the liver, the other main storage organ for iron, carrying the risk of free radical formation and tissue damage. REGULATION OF IRON HOMOEOSTASIS: Hepcidin, synthesised by hepatocytes in response to iron concentrations, inflammation, hypoxia and erythropoiesis, is the main iron-regulatory hormone. It binds ferroportin on enterocytes, macrophages and hepatocytes triggering its internalisation and lysosomal degradation. Inappropriate hepcidin secretion may lead to either iron deficiency or iron overload.

We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9). We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).

We conducted a retrospective collaborative study to cytogenetically characterize splenic marginal zone lymphoma (SMZL) and ascertain the prognostic value of chromosomal aberrations. Of 330 cases, 72% displayed an aberrant karyotype, 53% were complex, and 29% had a single aberration. The predominant aberrations were gains of 3/3q and 12q, deletions of 7q and 6q and translocations involving 8q/1q/14q. CD5 expression was detected in 39 of 158 cases (25%). The cytogenetic makeup of the CD5(+) group differed significantly from that of the CD5(-) group. Cases with unmutated IGHV were significantly associated with deletions of 7q and TP53. A strong association was noted between usage of the IGVH1-2 and deletion 7q, 14q alterations, and abnormal karyotype. On univariate analysis, patients with more than or equal to 2 aberrations, 14q alterations, and TP53 deletions had the shortest survival; 7q deletion did not affect survival. On multivariate analysis, cytogenetic aberrations did not retain prognostic significance; the parameters negatively affecting survival were hemoglobin and age. In conclusion, the cytogenetic profile of SMZL is distinct from other B-cell lymphomas. Complexity of the karyotype, 14q aberrations, and TP53 deletions are poor prognostic indicators and may be considered together with other clinicobiologic parameters to ascertain the prognosis of SMZL.

OBJECTIVES: To ascertain whether indicators of oxidative damage to lipids (malondialdehyde (MDA)) and proteins (protein carbonylation) are biomarkers of frailty, after adjusting for age, sex, and other possible confounders. DESIGN: Cross-sectional cohort study. SETTING: Community. PARTICIPANTS: Toledo Study for Healthy Aging participants (N = 742, aged 65-95), classified as frail (n = 54), prefrail (n = 278) and nonfrail (n = 410) according to the Fried criteria. MEASUREMENTS: Blood plasma was obtained using centrifugation (1,500 G, 15 minutes) and immediately frozen at -80°C. Plasma lipid peroxidation was determined by measuring the MDA formed from lipoperoxides using high-performance liquid chromatography and protein carbonylation was measured using Western blot. RESULTS: Age- and sex-adjusted levels of lipoperoxides (measured as MDA) and protein carbonylation in plasma proved to be related to frailty, even after including possible independent confounders. CONCLUSION: Circulating oxidative damage biomarkers, such as MDA and protein carbonylation, are related to frailty and not to age or sex. These parameters may be considered as potential biomarkers of frailty in the context of a multidisciplinary health-promoting approach for older adults.

Sulfonyl chlorides are inexpensive reactants extensively explored for functionalization, but never considered for radical hydrosulfonylation of alkenes. Herein, we report that tris(trimethylsilyl)silane is an ideal hydrogen atom donor enabling highly effective photoredox-catalyzed hydrosulfonylation of electron-deficient alkenes with sulfonyl chlorides. To increase the generality of this transformation, polarity-reversal catalysis (PRC) was successfully implemented for alkenes bearing alkyl substituents. This late-stage functionalization method tolerates a remarkably wide range of functional groups, is operationally simple, scalable, and allows access to building blocks which are important for medicinal chemistry and drug discovery.

BACKGROUND: Chronic non-specific neck pain is a frequent complaint. It is a recognized medical and socioeconomic problem and a frequent cause of job absenteeism. In recent years, case reports about myofascial pain syndrome (MPS) are emerging among patients suffering from pain. MPS is a regional pain syndrome characterized by myofascial trigger points (MTrP) in palpable taut bands of skeletal muscle that refer pain to a distance, and that can cause distant motor and autonomic effects. OBJECTIVE: To assess the prevalence of active and latent MTrPs in subjects suffering from chronic non-specific neck pain. DESIGN: A population-based cross-sectional descriptive study was carried out from January 2012 to December 2014. SETTING: Three primary healthcare centers in Alcalá de Henares, Madrid (Spain). SUBJECTS: Two hundred and twenty-four participants diagnosed by their family doctor with chronic non-specific neck pain. METHODS: Participants were examined by a physical therapist to determine the presence of MPS. Pain descriptions from the subjects and pain body diagrams guided the physical examination. The subjects were not given any information concerning MPS or other muscle pain syndromes. RESULTS: All participants presented with MPS. MTrPs of the trapezius muscles were the most prevalent, in 93.75% of the participants. The most prevalent active MTrPs were located right (82.1%) and left (79%) in the nearly-horizontal fibers of the upper trapezius muscle. Furthermore, active MTrPs in the levator scapulae, multifidi, and splenius cervicis muscles reached a prevalence of 82.14%, 77.68%, and 62.5%, respectively. CONCLUSIONS: MPS is a common source of pain in subjects presenting chronic non-specific neck pain.

Abstract Chronic neck pain attributed to a myofascial pain syndrome is characterized by the presence of muscle contractures referred to as myofascial trigger points. In this randomized, parallel-group, blinded, controlled clinical trial, we examined the effectiveness of deep dry needling (DDN) of myofascial trigger points in people with chronic nonspecific neck pain. The study was conducted at a public Primary Health Care Centre in Madrid, Spain, from January 2010 to December 2014. A total of 130 participants with nonspecific neck pain presenting with active myofascial trigger points in their cervical muscles were included. These participants were randomly allocated to receive: DDN plus stretching (n = 65) or stretching only (control group [n = 65]). Four sessions of treatment were applied over 2 weeks with a 6-month follow-up after treatment. Pain intensity, mechanical hyperalgesia, neck active range of motion, neck muscle strength, and perceived neck disability were measured at baseline, after 2 sessions of intervention, after the intervention period, and 15, 30, 90, and 180 days after the intervention. Significant and clinically relevant differences were found in favour of dry needling in all the outcomes (all P &lt; 0.001) at both short and long follow-ups. Deep dry needling and passive stretching is more effective than passive stretching alone in people with nonspecific neck pain. The results support the use of DDN in the management of myofascial pain syndrome in people with chronic nonspecific neck pain.

OBJECTIVE: Endoprostheses were inserted in cancer patients with superior vena cava syndrome to assess their effectiveness as first-choice, initial treatment for relief of symptoms. SUBJECTS AND METHODS: Wallstent prostheses (n = 73) of various lengths (5-14 cm; median, 7 cm) and diameters (10-16 mm; median, 16 mm) were inserted in 52 cancer patients (51 men, 1 woman; age range, 44-78 years; mean, 63 years) who were diagnosed and confirmed by cavography or phlebography as having superior vena cava syndrome. A single stent was sufficient in 37 patients, two stents were required in 11, three stents in two, and four stents in another two patients. Contraindications for the procedure were severe cardiopathy or coagulopathy. RESULTS: Resolution of symptoms was achieved in all patients within 72 hr. At follow-up, six obstructions, one partial migration to the right atrium, two incorrect placements, and four stent "shortenings" were noted. All were successfully resolved by repeated stenting. Symptom-free survival ranged from 2 days to 17 months (mean, 6.4 months). At the time of this writing, eight patients are alive and have patent stents. The rest have died from their cancer. CONCLUSION: The Wallstent vascular endoprosthesis is an effective initial treatment in superior vena cava syndrome of neoplastic origin. Morbidity and complications are minimal. Clinical relief of symptoms is rapid; therefore, the Wallstent endoprosthesis is highly recommended as the first choice for palliative treatment of superior vena cava syndrome, especially because the clinical decision for subsequent chemotherapy or radiotherapy or surgery is not in any way prejudiced.

BACKGROUND: Nowadays, 65-80% of pheochromocytoma and paraganglioma (PPGL) cases are explained by germline or somatic mutations in one of 22 genes. Several genetic testing algorithms have been proposed, but they usually exclude sporadic-PPGLs (S-PPGLs) and none include somatic testing. We aimed to genetically characterise S-PPGL cases and propose an evidence-based algorithm for genetic testing, prioritising DNA source. METHODS: The study included 329 probands fitting three criteria: single PPGL, no syndromic and no PPGL family history. Germline DNA was tested for point mutations in RET and for both point mutation and gross deletions in VHL, the SDH genes, TMEM127, MAX and FH. 99 tumours from patients negative for germline screening were available and tested for RET, VHL, HRAS, EPAS1, MAX and SDHB. RESULTS: Germline mutations were found in 46 (14.0%) patients, being more prevalent in paragangliomas (PGLs) (28.7%) than in pheochromocytomas (PCCs) (4.5%) (p=6.62×10(-10)). Somatic mutations were found in 43% of those tested, being more prevalent in PCCs (48.5%) than in PGLs (32.3%) (p=0.13). A quarter of S-PPGLs had a somatic mutation, regardless of age at presentation. Head and neck PGLs (HN-PGLs) and thoracic-PGLs (T-PGLs) more commonly had germline mutations (p=2.0×10(-4) and p=0.027, respectively). Five of the 29 metastatic cases harboured a somatic mutation, one in HRAS. CONCLUSIONS: We recommend prioritising testing for germline mutations in patients with HN-PGLs and T-PGLs, and for somatic mutations in those with PCC. Biochemical secretion and SDHB-immunohistochemistry should guide genetic screening in abdominal-PGLs. Paediatric and metastatic cases should not be excluded from somatic screening.

BACKGROUND: Pain after breast cancer therapy is a recognized complication found to have an adverse impact on patient's quality of life, increasing psychosocial distress. In recent years, case reports about myofascial pain syndrome are emerging in thoracic surgery as a cause of postsurgery pain. Myofascial pain syndrome is a regional pain syndrome characterized by myofascial trigger points in palpable taut bands of skeletal muscle that refers pain a distance, and that can cause distant motor and autonomic effects. OBJECTIVE: The objective of this study was to assess the incidence of myofascial pain syndrome prospectively 12 months after breast cancer surgery. METHODS: Each participant was assessed preoperatively, postoperatively between day 3 and day 5, and at 1, 3, 6, and 12 months after surgery. A physical therapist, expert in the diagnosis of myofascial pain syndrome, performed follow-up assessments. Pain descriptions by the patients and pain pattern drawings in body forms guided the physical examination. The patients were not given any information concerning myofascial pain or other muscle pain syndromes. RESULTS: One year follow-up was completed by 116 women. Of these, 52 women developed myofascial pain syndrome (44.8%, 95% confidence interval: 35.6, 54.3). CONCLUSION: Myofascial pain syndrome is a common source of pain in women undergoing breast cancer surgery that includes axillary lymph node dissection at least during the first year after surgery. Myofascial pain syndrome is one potential cause of chronic pain in breast cancer survivors who have undergone this kind of surgery.

OBJECTIVE: Self-expandable metal stents were inserted in cancer patients with superior vena cava (SVC) syndrome to assess their effectiveness as a primary treatment for symptom relief. SUBJECTS AND METHODS: Between January 1993 and June 2008, Wallstent prostheses (n = 208) were inserted in 149 cancer patients (137 men, 12 women; median age, 65 years; age range, 44-84 years) diagnosed as having SVC syndrome. A single stent was sufficient to restore vessel patency in 102 patients, two stents in 36, three stents in 10, and four stents in one. Survival data were calculated using Kaplan-Meier curves and multivariate analysis using the Cox regression method. RESULTS: Complete resolution of symptoms was achieved in 123 patients within 72 hours, partial resolution in 22 patients, and no response in only four patients. At follow-up, 30 complications were noted: 16 obstructions, four cases of thrombosis, one partial stent migration to the right atrium, two cases of incorrect stent placement, six stent "shortenings," and one case in which stent expansion was insufficient. All complications except two were successfully resolved by repeat stenting or by angioplasty. The median symptom-free survival was 6 months (range, 2 days-43 months). As of June 2008, eight patients were alive with patent stents. CONCLUSION: The Wallstent vascular endoprosthesis is an effective initial treatment in patients with SVC syndrome of neoplastic origin: Morbidity and complications are minimal, and clinical relief of symptoms is very rapid. Because the clinical decision for subsequent elective chemotherapy or radiation therapy is not prejudiced, stenting is a very effective initial step in the overall palliative treatment of patients with SVC syndrome.

Inherited platelet disorders are a heterogeneous group of rare diseases, caused by inherited defects in platelet production and/or function. Their genetic diagnosis would benefit clinical care, prognosis and preventative treatments. Until recently, this diagnosis has usually been performed via Sanger sequencing of a limited number of candidate genes. High-throughput sequencing is revolutionizing the genetic diagnosis of diseases, including bleeding disorders. We have designed a novel high-throughput sequencing platform to investigate the unknown molecular pathology in a cohort of 82 patients with inherited platelet disorders. Thirty-four (41.5%) patients presented with a phenotype strongly indicative of a particular type of platelet disorder. The other patients had clinical bleeding indicative of platelet dysfunction, but with no identifiable features. The high-throughput sequencing test enabled a molecular diagnosis in 70% of these patients. This sensitivity increased to 90% among patients suspected of having a defined platelet disorder. We found 57 different candidate variants in 28 genes, of which 70% had not previously been described. Following consensus guidelines, we qualified 68.4% and 26.3% of the candidate variants as being pathogenic and likely pathogenic, respectively. In addition to establishing definitive diagnoses of well-known inherited platelet disorders, high-throughput sequencing also identified rarer disorders such as sitosterolemia, filamin and actinin deficiencies, and G protein-coupled receptor defects. This included disease-causing variants in DIAPH1 (n=2) and RASGRP2 (n=3). Our study reinforces the feasibility of introducing high-throughput sequencing technology into the mainstream laboratory for the genetic diagnostic practice in inherited platelet disorders.

BACKGROUND AND AIMS: Alterations in short chain fatty acid metabolism, particularly butyrate, have been reported in inflammatory bowel disease, but results have been conflicting because of small study numbers and failure to distinguish disease type, activity or other variables such as diet. We performed a comparative assessment of the capacity of the microbiota for butyrate synthesis, by quantifying butyryl-CoA:acetate CoA-transferase [BCoAT] gene content in stool from patients with Crohn's disease [CD; n = 71], ulcerative colitis [UC; n = 58] and controls [n = 75], and determined whether it was related to active vs inactive inflammation, microbial diversity, and composition and/or dietary habits. METHODS: BCoAT gene content was quantified by quantitative polymerase chain reaction [qPCR]. Disease activity was assessed clinically and faecal calprotectin concentration measured. Microbial composition was determined by sequencing 16S rRNA gene. Dietary data were collected using an established food frequency questionnaire. RESULTS: Reduced butyrate-synthetic capacity was found in patients with active and inactive CD [p < 0.001 and p < 0.01, respectively], but only in active UC [p < 0.05]. In CD, low BCoAT gene content was associated with ileal location, stenotic behaviour, increased inflammation, lower microbial diversity, greater microbiota compositional change, and decreased butyrogenic taxa. Reduced BCoAT gene content in patients with CD was linked with a different regimen characterised by lower dietary fibre. CONCLUSIONS: Reduced butyrate-synthetic capacity of the microbiota is more evident in CD than UC and may relate to reduced fibre intake. The results suggest that simple replacement of butyrate per se may be therapeutically inadequate, whereas manipulation of microbial synthesis, perhaps by dietary means, may be more appropriate.