[Scapular fractures]. / Scapulafrakturen.

Scapular fractures are rare injuries that require different treatment strategies. Nondisplaced fractures and the majority of scapular body fractures can be treated conservatively, while surgical treatment should be considered for displaced fractures involving the glenoid. Displaced glenoid fractures of appropriate size and intra-articular step formation should be treated surgically. Different classification systems for scapular fractures can support the treatment decision. Postoperative and posttraumatic management should include early mobilization to achieve a good functional outcome. Clear recommendations and treatment algorithms at the evidence level are not available and long-term outcomes of scapular fractures are the subject of further investigation. The results published so far show good to excellent results for surgical and conservative treatment, depending on the type of fracture. Individual patient factors should be considered when planning treatment.

[Fracture sequelae type 2 of the proximal humerus-clinical results after arthroplasty]. / Frakturfolge Typ 2 des proximalen Humerus ­ klinische Ergebnisse nach endoprothetischer Therapie.

Locked dislocations of the glenohumeral joint are rare but often painful and are associated with limited range of motion in the shoulder. In patients of advanced age, arthroplasty is increasingly indicated as a surgical treatment option. Preoperatively, the direction of dislocation, the presence and extent of a glenoid defect, and the soft tissue situation (rotator cuff status, joint capsule) should be analyzed in a differentiated manner. Based on the above factors, we recommend the subclassification of type 2 according to Boileau: posterior locked dislocation (2a), anterior locked dislocation without glenoid defect (2b), and anterior locked dislocation with glenoid defect (2c). In the case of dorsally locked dislocation, a good clinical result can be achieved by using an anatomical endoprosthesis. For ventrally locked dislocations, we recommend using an inverse total endoprosthesis with, if necessary, bony glenoid reconstruction and transfer of the pectoralis major muscle.Level of evidence: IV.

[Fracture analysis, indication for endoprosthesis and implant selection in proximal humeral fractures]. / Frakturanalyse, Indikation zur Endoprothese und Implantatwahl bei proximaler Humerusfraktur.

Proximal humeral fractures (PHF) are the third most common fracture in humans and the incidence is increasing. There are basically three treatment strategies: conservative, joint-preserving reconstructive or joint-replacing procedures. In addition to fracture morphology, patient-specific and surgeon-specific factors are particularly important when deciding on treatment. The experience and training of the surgeon also play a decisive role. In the case of joint-preserving treatment, the risk of osteosynthesis failure and of sequelae of the fracture must always be assessed. If conservative or reconstructive treatment methods are not promising, the joint-replacing procedure is the treatment of choice. The anatomical fracture prosthesis is only indicated, if at all, for young patients with a destroyed humeral head with a preserved rotator cuff and large fragments of the tuberosities. In advanced age, the implantation of a reverse endoprosthesis is increasingly used for dislocated, multifragmentary PHF. In both procedures, the anatomical healing of the tuberosities has a significant impact on the functional outcome.

[Latissimus dorsi transfer with a modified single-incision Herzberg technique and description of its arthroscopic advancement]. / Latissimus-dorsi-Transfer in modifizierter Single-incision-Technik nach Herzberg und Beschreibung einer arthroskopischen Erweiterung.

OBJECTIVE: Latissimus dorsi transfer aims to reduce pain and improve function for irreparable tears of the posterosuperior rotator cuff by restoring the transversal force couple to improve external rotation and delaying superior migration of the humeral head. INDICATIONS: Surgery is advocated in patients with unbearable shoulder pain and limited external rotation caused by an irreparable posterosuperior rotator cuff tear. Usually, a latissimus transfer is recommended in the presence of superior migration of the humeral head, higher grade fatty infiltration of the rotator cuff and a restriction of range of motion and strength for abduction and external rotation. Advantages of the arthroscopically assisted technique are the missing need of detaching the deltoid from its origin, smaller incisions and therapy of concomitant intraarticular lesions. CONTRAINDICATIONS: Little pain and sufficient shoulder function in massive posterosuperior rotator cuff tears do not necessitate latissimus transfer. In the presence of subscapularis tears, osteoarthritis and deltoid dysfunction as well as shoulder stiffness tendon transfer are associated with inferior clinical outcomes. SURGICAL TECHNIQUE: Surgery is performed in prone position. The incision is made about 5 cm caudal of the posterolateral corner of the acromion and extends over 6 cm at the inferior border of the deltoid muscle. After exploration and protection of the axillary and radial nerve the latissimus tendon is peeled off of the humerus. The medial part of the latissimus is then mobilized to gain length for the later transfer. Afterwards the footprint of the infraspinatus is visualized and debrided. Two or three suture anchors are placed into the posterosuperior aspect of the greater tuberosity. The sutures are stitched through the tendon in a horizontal mattress stitch configuration and the tendon tied onto the bone. In arthroscopic advancement, the patient is placed in an upright beach-chair position with the arm attached to an arm holder. After debridement of the supraspinatus and infraspinatus footprint, arthroscopic preparation at the anterior border of the subscapularis tendon is performed. The latissimus tendon is visualized and detached with electrocautery. Afterwards the interval between posterior rotator cuff and deltoid muscle is prepared to allow the transfer of the latissimus tendon to the posterosuperior footprint. This marks the transition to the open approach, in which the arm is placed in a flexed and internally rotated position. POSTOPERATIVE MANAGEMENT: Immobilization in a shoulder sling for 3 weeks. Early passive range of motion (ROM: flexion 30°, internal rotation 60°, abduction 0°, external rotation 0°) was immediately allowed. After 3 weeks, passive ROM was increased to 90° of flexion, 60° of abduction, whereas external rotation was still restricted. After 7 weeks, free passive ROM and after 8 weeks active ROM (assisted) were allowed. RESULTS: In all, 67 patients (mean age 63 years) were examined 54 months (±â€¯28) after open transfer of the latissimus dorsi tendon. Constant score improved from 24 (±â€¯6) points to 68 (±â€¯17) points. Active flexion increased from 83° (±â€¯47°) to 144° (±â€¯35°), abduction from 69° (±â€¯33°) to 134° (±â€¯42°) and external rotation from 24° (±â€¯18°) to 35° (±â€¯21°). The VAS score decreased from 6.3 (±â€¯1.1) to 1.8 (±â€¯2). However, osteoarthritis worsened over time and the Hamada-Fukuda stage increased from 1.4 to 2.1 and the acromihumeral distance decreased from 7.9 (±â€¯2.6) to 5.1 (±â€¯2.2) at final follow-up.

[Mechanisms of cardiotoxicity of oncological therapies]. / Mechanismen der Kardiotoxizität onkologischer Therapien.

BACKGROUND: Oncological therapies show a number of undesired adverse effects on the cardiovascular system. In particular, the side effects of recently established oncological therapies are incompletely understood and clinical data are lacking in the interpretation of novel cardiac complications. OBJECTIVE: This article provides a short overview of the mechanisms of cardiac side effects of certain oncological therapies. MATERIAL AND METHODS: The review is mainly based on data from preclinical studies. RESULTS: Numerous toxic side effects have already been described and investigated in preclinical models. For certain groups of drugs (e.g. anthracyclines, tyrosine kinase inhibitors and immune checkpoint inhibitors) the underlying molecular mechanisms are still not fully understood. CONCLUSION: An improved understanding of the molecular mechanism involved in cardiotoxicity might help improve the quality of clinical decisions. Additionally, it will provide new insights into the pathophysiology of cardiac diseases. The aim is to use the results of translational research and to clinically implement them in suitable cardio-oncology units.

Establishing an oncocardiology service.

Oncocardiology is an emerging field in cardiovascular healthcare. Besides establishing surveillance and follow-up strategies for cancer patients, it will be essential to set up specialized oncocardiology services. However, there is a lack of clinical studies to give evidence-based recommendations regarding cardiological diagnostic and therapeutic approaches for cancer patients. An oncocardiology service is a patient-centered structure that aims to integrate research and interdisciplinary patient care to bridge this gap. We discuss the current challenges in developing an oncocardiology service and review the literature on this topic. We further provide an overview of the essential diagnostic tools and upcoming ethical issues to be considered in the management of oncology patients.

Relative effectiveness of insects versus hummingbirds as pollinators of Rubiaceae plants across elevation in Dominica, Caribbean.

Most angiosperms rely on animal pollination for reproduction, but the dependence on specific pollinator groups varies greatly between species and localities. Notably, such dependence may be influenced by both floral traits and environmental conditions. Despite its importance, their joint contribution has rarely been studied at the assemblage level. At two elevations on the Caribbean island of Dominica, we measured the floral traits and the relative contributions of insects versus hummingbirds as pollinators of plants in the Rubiaceae family. Pollinator importance was measured as visitation rate (VR) and single visit pollen deposition (SVD), which were combined to assess overall pollinator effectiveness (PE). In the wet and cool Dominican highland, we found that hummingbirds were relatively more frequent and effective pollinators than insects, whereas insects and hummingbirds were equally frequent and effective pollinators at the warmer and less rainy midelevation. Furthermore, floral traits correlated independently of environment with the relative importance of pollinators, hummingbirds being more important in plant species having flowers with long and wide corollas producing higher volumes of dilute nectar. Our findings show that both environmental conditions and floral traits influence whether insects or hummingbirds are the most important pollinators of plants in the Rubiaceae family, highlighting the complexity of plant-pollinator systems.

Changes in the incidence and bacterial aetiology of paediatric parapneumonic pleural effusions/empyema in Germany, 2010-2017: a nationwide surveillance study.

OBJECTIVES: Parapneumonic pleural effusions/empyema (PPE/PE) are severe complications of community-acquired pneumonia. We investigated the bacterial aetiology and incidence of paediatric PPE/PE in Germany after the introduction of universal pneumococcal conjugate vaccine (PCV) immunization for infants. METHODS: Children <18 years of age hospitalized with pneumonia-associated PPE/PE necessitating pleural drainage or persisting >7 days were reported to the German Surveillance Unit for Rare Diseases in Childhood between October 2010 and June 2017. All bacteria detected in blood or pleural fluid (by culture/PCR) were included, with serotyping for Streptococcus pneumoniae. RESULTS: The median age of all 1447 PPE/PE patients was 5 years (interquartile range 3-10). In 488 of the 1447 children with PPE/PE (34%), 541 bacteria (>40 species) were detected. Aerobic gram-positive cocci accounted for 469 of 541 bacteria detected (87%); these were most frequently Streptococcus pneumoniae (41%), Streptococcus pyogenes (19%) and Staphylococcus aureus (6%). Serotype 3 accounted for 45% of 78 serotyped S. pneumoniae strains. Annual PPE/PE incidence varied between 14 (95%CI 12-16) and 18 (95%CI 16-21) PPE/PE per million children. Incidence of S. pneumoniae PPE/PE decreased from 3.5 (95%CI 2.5-4.6) per million children in 2010/11 to 1.5 (95%CI 0.9-2.4) in 2013/14 (p 0.002), followed by a re-increase to 2.2 (95%CI 1.5-3.2) by 2016/17 (p 0.205). CONCLUSIONS: In the era of widespread PCV immunization, cases of paediatric PPE/PE were still caused mainly by S. pneumoniae and, increasingly, by S. pyogenes. The re-increase in the incidence of PPE/PE overall and in S. pneumoniae-associated PPE/PE indicates ongoing changes in the bacterial aetiology and requires further surveillance.

Effects of isoflavones on breast tissue and the thyroid hormone system in humans: a comprehensive safety evaluation.

Isoflavones are secondary plant constituents of certain foods and feeds such as soy, linseeds, and red clover. Furthermore, isoflavone-containing preparations are marketed as food supplements and so-called dietary food for special medical purposes to alleviate health complaints of peri- and postmenopausal women. Based on the bioactivity of isoflavones, especially their hormonal properties, there is an ongoing discussion regarding their potential adverse effects on human health. This review evaluates and summarises the evidence from interventional and observational studies addressing potential unintended effects of isoflavones on the female breast in healthy women as well as in breast cancer patients and on the thyroid hormone system. In addition, evidence from animal and in vitro studies considered relevant in this context was taken into account along with their strengths and limitations. Key factors influencing the biological effects of isoflavones, e.g., bioavailability, plasma and tissue concentrations, metabolism, temporality (pre- vs. postmenopausal women), and duration of isoflavone exposure, were also addressed. Final conclusions on the safety of isoflavones are guided by the aim of precautionary consumer protection.

Control of the coherence behavior in a SFG interferometer through the multipump phases command.

In this paper, we report on a novel method to control the coherence behavior in a sum frequency generation interferometer powered by two independent pump lines. At the output of the interferometer, the two incoherent fringe patterns must be superimposed to maximize the contrast. The first step consists in canceling the differential group delay. The second one uses the phase control on one pump to synchronize the fringe patterns. This innovative method is experimentally demonstrated with a setup involving a 1544 nm signal and two pump lines around 1064 nm leading to a converted signal around 630 nm. It can be easily extended to a greater number of pump lines.

[Arthroscopic fracture treatment of the shoulder joint]. / Arthroskopische Frakturversorgung des Schultergelenks.

In recent years, the understanding of shoulder fractures has changed due to the progress of arthroscopy. In addition to the cosmetic result, the access morbidity, particularly the integrity of the subscapularis muscle in glenoid and scapular fractures, must be mentioned as an advantage of a minimally invasive approach. Furthermore, necessary secondary interventions, e. g. hook plate removal, can be prevented or minimized by modern implants and arthroscopic techniques.However, the available data and publications are almost exclusively limited to technical notes or small case series, so statements about faster recreation or potential reduction of infection risk cannot be made. Whether addressing concomitant injuries has an effect on the clinical and functional outcome is also unclear at the present time.

Contamination of organic nutrient sources with potentially toxic elements, antibiotics and pathogen microorganisms in relation to P fertilizer potential and treatment options for the production of sustainable fertilizers: A review.

Organic nutrient sources such as farmyard manure, sewage sludge, their biogas digestates or other animal by-products can be valuable fertilizers delivering organic matter to the soil. Currently, especially phosphorus (P) is in the focus of research since it is an essential plant nutrient with finite resources, estimated to last only for some more decades. Efficient utilization of organic P sources in agriculture will help to preserve P resources and thereby has the potential to close nutrient cycles and prevent unwanted P-losses to the environment, one of the major causes for eutrophication of water bodies. Unfortunately, organic P sources usually contain also various detrimental substances, such as potentially toxic elements or organic contaminants like pharmaceuticals as well as pathogenic microorganisms. Additionally, the utilization of some of these substrates such as sewage sludge or animal by-products is legally limited in agriculture because of the potential risk to contaminate sites with potentially toxic elements and organic contaminants. Thus, to close nutrient cycles it is important to develop solutions for the responsible use of organic nutrient sources. The aim of this review is to give an overview of the contamination of the most important organic nutrient sources with potentially toxic elements, antibiotics (as one important organic contaminant) and pathogenic microorganisms. Changes in manure and sewage sludge management as well as the increasing trend to use such substrates in biogas plants will be discussed with respect to potential risks posed to soils and water bodies. Some examples for abatement options by which contamination can be reduced to produce P fertilizers with high amounts of plant available P forms are presented.

Risk of melanocytic nevi and nonmelanoma skin cancer in children after allogeneic hematopoietic stem cell transplantation.

There is a known increased risk of skin cancer in the adult population after hematopoietic stem cell transplantation (HSCT). However, late dermatologic effects that children may experience after HSCT have not been well described. The primary objective of this study was to characterize nevi and skin cancers affecting children after allogeneic HSCT. A cross-sectional cohort study of 85 pediatric HSCT recipients and 85 controls matched for age, sex and skin phototype was performed at a single institution. All participants underwent a full skin examination. Median age at study visit was 13.8 years in HSCT patients with median time post-HSCT of 3.6 years. HSCT patients had significantly more nevi than control patients (median (range): 44 (0-150) vs 11 (0-94), P<0.0001). HSCT patients also had significantly more nevi >5 mm in diameter and atypical nevi than controls. Factors associated with increased nevus count included malignant indication for HSCT, pretransplant chemotherapy, TBI exposure and myeloablative conditioning. A total of 16.5% of HSCT patients developed cancerous, precancerous lesions and/or lentigines. Our study suggests that pediatric HSCT recipients have an increased risk of benign and atypical melanocytic proliferations and nonmelanoma skin cancer that can manifest even during childhood.

GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes.

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.

Risk and other factors associated with toxoplasmosis and toxocariasis in pregnant women from southern Brazil.

Toxoplasmosis causes complications during pregnancy that have serious effects on fetal development. Thus far, toxocariasis has been reported to spread only via vertical transmission. Nonetheless, the population of pregnant women is also exposed to this infection. Co-infection with both Toxoplasma gondii and Toxocara spp. has been reported in children, but there are no reports of co-infection in the population of pregnant women. The aim of this study was to determine the prevalence of co-infection with T. gondii and Toxocara spp. in pregnant women at a university hospital in southern Brazil, and to identify the risk factors associated with infection by both parasites. Two hundred pregnant women were tested for the presence of anti-T. gondii and anti-Toxocara spp. antibodies and were asked to complete an epidemiological questionnaire. In this study, the co-infection rate observed in the total population of pregnant women was 8%. In addition, women with a positive result for a serology test for Toxocara spp. were at increased risk of infection by T. gondii (P = 0.019). Co-infection with both parasites in pregnant women was associated with low birth weights in neonates. The similar modes of transmission of both parasites could explain the co-infection. Only a few previous studies have investigated this phenomenon. The findings of the present study emphasize the importance of serological diagnosis during prenatal care and further research in this area to identify risk factors associated with this co-infection, and the possible implications of this co-infection during pregnancy and on the health of newborns.

Safety and efficacy of insulin degludec/liraglutide (IDegLira) added to sulphonylurea alone or to sulphonylurea and metformin in insulin-naïve people with Type 2 diabetes: the DUAL IV trial.

AIM: To investigate the safety and efficacy of insulin degludec/liraglutide (IDegLira), a novel combination product, as add-on therapy for people with Type 2 diabetes uncontrolled on sulphonylurea therapy. METHODS: In this 26-week, double-blind trial, adults with Type 2 diabetes [HbA1c 53-75 mmol/mol (7.0-9.0%)] were randomized to IDegLira (n = 289) or placebo (n = 146) as add-on to pre-trial sulphonylurea ± metformin, titrating to a fasting glycaemic target of 4.0-6.0 mmol/l. Treatment initiation was at 10 dose steps, and maximum dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). RESULTS: The mean HbA1c decreased from 63 mmol/mol (7.9%) to 46 mmol/mol (6.4%) with IDegLira and to 57 mmol/mol (7.4%) with placebo [estimated treatment difference -11 mmol/mol (95% CI -13; -10) or -1.02% (95% CI -1.18; -0.87); P < 0.001]. The HbA1c target of 53 mmol/mol (<7%) was achieved by 79.2% of participants in the IDegLira group vs 28.8% in the placebo group [estimated odds ratio 11.95 (95% CI 7.22; 19.77); P < 0.001]. Mean weight change was +0.5 kg with IDegLira vs -1.0 kg with placebo [estimated treatment difference 1.48 kg (95% CI 0.90; 2.06); P < 0.001]. Confirmed hypoglycaemia occurred in 41.7 and 17.1% of IDegLira- and placebo-treated participants, respectively, with rates of 3.5 vs 1.4 events/patient-years of exposure [estimated rate ratio 3.74 (95% CI 2.28; 6.13); P < 0.001]. IDegLira was generally well tolerated. The rates of serious adverse events were 20.3 and 8.0 per 100 patient-years of exposure with IDegLira and placebo, respectively, without obvious patterns in the type of events. CONCLUSIONS: IDegLira can be used in people uncontrolled with sulphonylurea ± metformin to improve efficacy with a safety profile in line with previous DUAL trials.

Are physicians prepared for whole genome sequencing? a qualitative analysis.

Although the integration of whole genome sequencing (WGS) into standard medical practice is rapidly becoming feasible, physicians may be unprepared to use it. Primary care physicians (PCPs) and cardiologists enrolled in a randomized clinical trial of WGS received genomics education before completing semi-structured interviews. Themes about preparedness were identified in transcripts through team-based consensus-coding. Data from 11 PCPs and 9 cardiologists suggested that physicians enrolled in the trial primarily to prepare themselves for widespread use of WGS in the future. PCPs were concerned about their general genomic knowledge, while cardiologists were concerned about how to interpret specific types of results and secondary findings. Both cohorts anticipated preparing extensively before disclosing results to patients by using educational resources with which they were already familiar, and both cohorts anticipated making referrals to genetics specialists as needed. A lack of laboratory guidance, time pressures, and a lack of standards contributed to feeling unprepared. Physicians had specialty-specific concerns about their preparedness to use WGS. Findings identify specific policy changes that could help physicians feel more prepared, and highlight how providers of all types will need to become familiar with interpreting WGS results.

Nail dystrophy, edema, and eosinophilia: harbingers of severe chronic GVHD of the skin in children.

The prognostic value of adnexal findings in chronic GVHD (cGVHD) has not been investigated in children. Dermatologic examinations were performed in a severe cohort of 11 children with skin cGVHD seen over a 2-year period. Findings were compared with 25 additional patients with skin cGVHD and 97 control patients. In 36 patients with skin cGVHD, nail dystrophy was present in 45% of patients, and was significantly associated with sclerotic disease and lung cGVHD. Pterygium inversum unguis (PIU) was associated with severe lung disease, with significantly lower % predicted FVC and FEV1 in those with PIU than those without. Forty-four percent of GVHD patients had preceding peripheral edema and 56% had preceding peripheral eosinophilia. Peripheral edema and eosinophilia were significantly associated with sclerotic cGVHD and persisted until the diagnosis of cGVHD in all patients. Comparison of data with control patients showed that incidence of nail dystrophy, incidence of peripheral edema and mean peak peripheral eosinophil count of patients with skin cGVHD was significantly higher than those without cGVHD. This study suggests that nail dystrophy, persistent peripheral edema and persistent peripheral eosinophilia are harbingers of severe cGVHD of the skin in children. The presence of PIU may be a harbinger of severe lung involvement.

The robustness of the weak selection approximation for the evolution of altruism against strong selection.

The weak selection approximation of population genetics has made possible the analysis of social evolution under a considerable variety of biological scenarios. Despite its extensive usage, the accuracy of weak selection in predicting the emergence of altruism under limited dispersal when selection intensity increases remains unclear. Here, we derive the condition for the spread of an altruistic mutant in the infinite island model of dispersal under a Moran reproductive process and arbitrary strength of selection. The simplicity of the model allows us to compare weak and strong selection regimes analytically. Our results demonstrate that the weak selection approximation is robust to moderate increases in selection intensity and therefore provides a good approximation to understand the invasion of altruism in spatially structured population. In particular, we find that the weak selection approximation is excellent even if selection is very strong, when either migration is much stronger than selection or when patches are large. Importantly, we emphasize that the weak selection approximation provides the ideal condition for the invasion of altruism, and increasing selection intensity will impede the emergence of altruism. We discuss that this should also hold for more complicated life cycles and for culturally transmitted altruism. Using the weak selection approximation is therefore unlikely to miss out on any demographic scenario that lead to the evolution of altruism under limited dispersal.