Synergistic effects of organic carbon and silica in preserving structural stability of drying soils.

Predicted climate warming and prolonged droughts pose a threat to the soil structure as organic carbon losses weaken the stability of soil aggregates. Well-structured soils are important for storage and movement of water, solutes, and air, the development of plant roots, as habitat for soil organisms, and the microbial activity. Structural stability is measured in terms of hydro-mechanical properties. This study compares effects of amorphous silica with those of organic carbon on stability parameters during drying of aggregates from relatively finer- and coarser-textured soils. Silica amendment enhanced the positive effect of organic carbon on structural stability in terms of the tensile strength. Synergistic effects between silica and organic carbon in soil colloids appear to dynamically alter aggregate density and friability (i.e., ability to crumble) during drying. Silica together with organic carbon could help soil management to reduce negative effects of predicted prolonged droughts on soil structure and stability.

Transcutaneous Osseointegrated Prosthesis Systems (TOPS) for Rehabilitation After Lower Limb Loss: Surgical Pearls.

Background: The biology of osseointegration of any intramedullary implant depends on the design, the press-fit anchoring, and the loading history of the endoprosthesis. In particular, the material and surface of the endoprosthetic stem are designed to stimulate on- and in-growth of bone as the prerequisite for stable and long-lasting integration1-8. Relative movement between a metal stem and the bone wall may stimulate the formation of a connective-tissue interface, thereby increasing the risk of peri-implant infections and implant loss9-12. The maximum achievable press-fit (i.e., the force closure between the implant and bone wall) depends on the diameter and length of the residual bone and thus on the amputation level. Beyond this, the skin-penetrating connector creates specific medical and biological challenges, especially the risk of ascending intramedullary infections. On the one hand, bacterial colonization of the skin-penetrating area (i.e., the stoma) with a gram-positive taxon is obligatory and almost impossible to avoid9,10. On the other hand, a direct structural and functional connection between the osseous tissue and the implant, without intervening connective tissue, has been shown to be a key for infection-free osseointegration11,12. Description: We present a 2-step implantation process for the standard Endo-Fix Stem (ESKA Orthopaedic Handels) into the residual femur and describe the osseointegration of the prosthesis13. In addition, we demonstrate the single-step implantation of a custom-made short femoral implant and a custom-made humeral BADAL X implant (OTN Implants) in a patient who experienced a high-voltage injury with the loss of both arms and the left thigh. Apart from the standard preparation procedures (e.g., marking the lines for skin incisions, preparation of the distal part of the residual bone), special attention must be paid when performing the operative steps that are crucial for successful osseointegration and utilization of the prosthesis. These include shortening of the residual bone to the desired length, preparation of the intramedullary cavity for hosting of the prosthetic stem, precise trimming of the soft tissue, and wound closure. Finally, we discuss the similarities and differences between the Endo-Fix Stem and the BADAL X implant in terms of their properties, intramedullary positioning, and the mechanisms leading to successful osseointegration. Alternatives: Socket prostheses for transfemoral or transtibial amputees have been the gold standard for decades. However, such patients face many challenges to recover autonomous mobility, and an estimated 30% of all amputees report unsatisfactory rehabilitation and 10% cannot use a socket prosthesis at all. Rationale: Transcutaneous osseointegrated prosthetic systems especially benefit patients who are unable to tolerate socket suspension systems, such as those with short residual limbs and/or bilateral limb loss. The use of a firmly integrated endoprosthetic stem allows patients and surgeons to avoid many of the limitations associated with conventional socket prostheses, such as the need to continually fit and refit the socket to match an ever-changing stump6,14-19. Discussion between patients who are considering an osseointegrated prosthesis and those who have already received one ("peer patients") has proven to be a powerful tool to prevent unrealistic expectations. Patients with a transhumeral amputation especially benefit from the stable connection between the residual limb and exoprosthesis. Motion of the affected and even the contralateral shoulder is no longer impaired, as straps and belts are dispensable. Furthermore, transmission of myoelectric signals from surrounding muscles to the prosthesis is fundamentally improved. However, comorbidities such as diabetes mellitus or peripheral arterial disease require careful counseling, even if these conditions were not responsible for the loss of the limb. Transcutaneous osseointegrated prosthetic systems for replacement of an upper or lower limb might not be an option in patients who are unable, for any reason, to take adequate care of the stoma. Expected Outcomes: Despite subtle differences between the systems utilized for the intramedullary anchoring of the prosthetic stem, all data indicate that mobility and quality of life significantly increase while the frequency of stoma infections is remarkably low as long as the patient is able to follow simple postoperative care protocols2-5,9,10,13-19. Important Tips: The impaction pressure of the implant depends on the diameter of the implant and the quality of the residual bone (i.e., the time interval between the amputation and the implantation of the prosthetic stem). The extent of reaming of the inner cortex of the residual bone must be adapted to these conditions. The standard Endo-Fix Stem and BADAL X implant are both slightly curved to adapt to the physiological shape of the femur. Thus, the surgeon must be sure to insert the implant in the right position and at the correct rotational alignment. When preparing a short femoral stump, carefully identify the exact transection level in order to obtain enough bone stock to anchor the implant in the correct intramedullary position for an additional locking screw into the femoral neck and head. Depending on the residual length of the humerus and the press-fit stability of the implant, the utilization of locking screws is optional, as a notch at the distal end of the implant guarantees primary rotational stability. Acronyms and Abbreviations: TOPS = transcutaneous osseointegrated prosthesis systemsEEP = endo-exo prosthesisMRSA = methicillin-resistant staphylococcus aureusa.p. = anteroposteriorK-wire = Kirschner wireCT = computed tomographyDCA = double conus adapterOFP = osseointegrated femur prosthesis.

[A boy with a painful lump in the right inguinal region]. / Een jongen met pijnlijke zwelling in lies.

A 6-year-old male, with no history of importance, was seen in the Emergency Department, presenting with a painful lump in the right inguinal region since four days. An ultrasound revealed a torsion of an ectopical testis. Surgery showed a necrotic right testicle and a right orchiectomy was performed.

Knowing the entire story - a focus group study on patient experiences with chronic Lyme-associated symptoms (chronic Lyme disease).

BACKGROUND: Healthcare providers frequently struggle to provide effective care to patients with chronic Lyme-associated symptoms (chronic Lyme disease, CLD), potentially causing these patients to feel misunderstood or neglected by the healthcare system. This study is the first to use a combined medical and communication science approach, and aims to assess patients' experiences with CLD & CLD-related care, identify themes and repertories in these patients' narrations, and provide potential ways to improve communication with them. METHODS: Informed by the principles of 'clean language', we conducted focus groups with self-identified CLD patients (N = 15). We asked participants about their experiences with CLD and CLD-related healthcare. We performed thematic analyses using a bottom-up approach based in discourse analysis. We also sought to identify specific types of verbalizations (repertoires) across themes. RESULTS: Participants thematised a heterogeneous set of CLD-associated symptoms, which they frequently labelled as 'invisible' to others. Their illness significantly affected their daily lives, impacting their work, social activities, relationships with loved ones, hobbies and other means of participating in society. Negative experiences with healthcare providers were near-universal, also in patients with short-lived CLD-associated symptoms. Verbalizations were notable for frequent use of communicative modes that implicitly create common ground between participants and that give a certain validity to personal experiences (impersonal 'you' and other forms of presupposition). CONCLUSION: Central themes found in CLD patients' communication are 1. the experience of significant symptoms, 2. for which adequate relief is only rarely found from conventional medical practitioners, and 3. that are largely invisible to the outside world. Verbalizing these themes, patients use various repertoires for their shared experiences, such as a feeling of abandonment or not being heard by the medical system, feelings of loss with respect to their previous health, and the idea that they might have been better off had they been diagnosed sooner. Working with these repertoires will enable healthcare providers to establish a shared perspective with their CLD patients, thus engaging in more fruitful doctor-patient communication. We hypothesize that these findings are not unique to CLD, but may also be applicable to other conditions with an uncertain aetiology, such as Long COVID.

[Functional rehabilitation after transfemoral amputation : Shaft prosthesis or endo-exo prosthesis?] / Funktionelle Rehabilitation nach Oberschenkelamputation : Schaftprothese oder Endo-Exo-Prothese?

BACKGROUND: After transfemoral amputation a prosthesis is required to restore autonomous standing and bipedal locomotion. Attachment of the prosthesis can be achieved either classically via socket suspension with a shaft in the stump or directly via implantation of an intramedullary transcutaneous femoral prosthesis (osseointegrated prosthesis). AIM: A fully instrumented gait analysis should enable objectification of the anticipated advantages of the EEP with respect to the gait pattern and individual mobility. MATERIAL AND METHODS: In two patients with a unilateral transfemoral amputation a comprehensive gait analysis was carried out prior to and 6 months (patient 1) or 11 and 20 months (patient 2) after switching from a socket prosthesis to an EEP. This was carried out in the Gait Realtime Analysis Interactive Lab (GRAIL), a fully instrumented gait laboratory with virtual reality and enables assessment close to the conditions of daily life. RESULTS: In both cases the gait analysis confirmed the advantages associated with an EEP for the transmission of force to the prosthesis and the accompanying improvement in gait symmetry.

[A closer look at the concept of positive health]. / Het concept 'positieve gezondheid' nader bekeken.

'Positive health' is a new concept that arose in response to shortcomings in the broad WHO definition of health. It has similarities with earlier holistic health concepts. The question is what 'positive health' adds for medical practice. On the one hand, the concept rightly emphasizes the gradual and dimensional character of health and the importance of (appealing to) people's resilience. On the other hand, there are also disadvantages. The comprehensive nature of the concept can lead to medicalization of social- and life-problems, and the emphasis on adaptation and self-management can contribute to individualization of health. In practice, the concept offers starting points for health policy and can promote cooperation across borders. For doctor and patient, the question is whether the concept adds much to, for example, the biopsychosocial model. The focus on resilience is a positive innovation, but it does not remove practical obstacles to a broad view of health.

[Clinical decision-making: from diagnosis to prognosis-oriented approach]. / Klinische besluitvorming.

Traditionally, diagnosis is the basis for clinical decision-making and regarded as the guide to prognosis and treatment. Although some patients may particularly benefit such a diagnosis-oriented approach (e.g., patients with acute pathology for which effective treatment is available), this approach is not suitable or sufficient for others (e.g., patients without a diagnosis, patients with a diagnosis for which no treatment is available, and patients for whom the current treatment is insufficient). Furthermore, other factors than diagnosis or diagnosis-guided treatment are likely to influence an individual's outcome (prognosis), including biological, clinical, and social factors. The authors propose a prognosis-oriented approach as an alternative starting point for medical decision-making: not only ask yourself 'what is the explanation for my patient's complaint?', but also 'which factors contribute to the future outcome of this complaint?' and 'can I address these to benefit my patient's outcome?'.

[Chronic Lyme disease: hype or hypothesis?] / Chronische lymeziekte.

There's an on-going discussion about chronic Lyme Disease: are the persisting symptoms some patients experience due to an inadequately treated Borrelia infection or is something else going on? In 2017 the National Lyme Disease Centre (NLe) has been established in the Netherlands. Two university medical centres, the RIVM and the Lyme Organization participate in the NLe where diagnostics and treatment are offered to patients and research into Lyme disease is carried out. Ideally, collaboration between doctors, researchers and patients leads to research that addresses relevant and urgent questions. Regarding chronic Lyme disease not as a hype but a hypothesis that needs to be verified or falsified, could help both doctors and patients, assuming that they can conclude together that some notions might have seemed rational, but nonetheless have to be discarded based on the results of sound scientific research. That might open new ways to explore treatment of persisting symptoms.

Energy mapping of the genetic code and genomic domains: implications for code evolution and molecular Darwinism.

When the iconic DNA genetic code is expressed in terms of energy differentials, one observes that information embedded in chemical sequences, including some biological outcomes, correlate with distinctive free energy profiles. Specifically, we find correlations between codon usage and codon free energy, suggestive of a thermodynamic selection for codon usage. We also find correlations between what are considered ancient amino acids and high codon free energy values. Such correlations may be reflective of the sequence-based genetic code fundamentally mapping as an energy code. In such a perspective, one can envision the genetic code as composed of interlocking thermodynamic cycles that allow codons to 'evolve' from each other through a series of sequential transitions and transversions, which are influenced by an energy landscape modulated by both thermodynamic and kinetic factors. As such, early evolution of the genetic code may have been driven, in part, by differential energetics, as opposed exclusively by the functionality of any gene product. In such a scenario, evolutionary pressures can, in part, derive from the optimization of biophysical properties (e.g. relative stabilities and relative rates), in addition to the classic perspective of being driven by a phenotypical adaptive advantage (natural selection). Such differential energy mapping of the genetic code, as well as larger genomic domains, may reflect an energetically resolved and evolved genomic landscape, consistent with a type of differential, energy-driven 'molecular Darwinism'. It should not be surprising that evolution of the code was influenced by differential energetics, as thermodynamics is the most general and universal branch of science that operates over all time and length scales.

Fracture prevention by screening for high fracture risk: a systematic review and meta-analysis.

This systematic review and meta-analysis showed a significant reduction of (major) osteoporotic fractures and hip fractures after screening using fracture risk assessment and bone densitometry compared with usual care. The results indicate that screening is effective for fracture risk reduction, especially hip fractures. To perform a systematic review and meta-analysis of population screening for high fracture risk on fracture prevention compared with usual care. MEDLINE and Embase were searched for studies published until June 20th 2019. Randomized studies were selected that screened for high fracture risk using at least bone densitometry, screened in a general population, provided subsequent treatment with anti-osteoporosis medication, had a usual care group as comparator, and had at least one fracture-related outcome (all fractures, (major) osteoporotic fractures, or hip fractures). The primary assessment was the hazard ratio (HR) for fracture-related outcomes. All-cause mortality was a secondary outcome. Random-effects models were used to estimate pooled HRs. We identified 1186 potentially eligible articles and included three randomized studies: the ROSE study, the SCOOP study, and the SOS with a total number of N = 42,009 participants. Respectively, 11%, 15%, and 18% of the participants in the intervention group started medication. Meta-analysis showed a statistically significant and clinically relevant reduction of osteoporotic fractures (HR = 0.95, 95% confidence interval (CI) = 0.89-1.00), major osteoporotic fractures (HR = 0.91; 95%CI = 0.84-0.98), and hip fractures (HR = 0.80; 95%CI = 0.71-0.91), but no reduction of all fractures (HR = 0.95; 95%CI = 0.89-1.02). The pooled HR for the secondary outcome all-cause mortality was 1.04 (95% CI = 0.95-1.14). Numbers needed to screen to prevent one fracture were 247 and 272 for osteoporotic fractures and hip fractures, respectively (corresponding to 113 and 124 performed bone densitometry examinations, and 25 and 28 persons being treated). This meta-analysis showed that population screening is effective to reduce osteoporotic fractures and hip fractures. Implementation of screening in older women should be considered as serious option to prevent osteoporotic fractures, especially hip fractures.

Amplitude-Integrated EEG and Cerebral Near-Infrared Spectroscopy in Cooled, Asphyxiated Infants.

OBJECTIVE: To assess the predictive value of amplitude-integrated electroencephalography EEG (aEEG) and near-infrared spectroscopy (NIRS) during therapeutic hypothermia. PATIENTS AND METHODS: We studied 39 cooled, asphyxiated infants. We assessed aEEG and calculated mean regional cerebral oxygen saturation (rcSO2) during and after treatment. At 30 months, we performed a neurological examination and administered the Bayley Scales of Infant and Toddler Development, 3rd edition. We calculated the odds ratios (ORs) of abnormal aEEG and rcSO2 for severely abnormal outcome. RESULTS: At 6 and 12 hours, severely abnormal aEEGs predicted severely abnormal outcomes (OR, 7.7 [95% confidence interval, CI, 1.39-42.6] and 24.4 [95% CI 4.2-143] respectively), as did epileptic activity (OR 28.9, 4.6-183). During the first 48 hours, rcSO2 was not associated with outcome, but at 72 hours after birth and after rewarming it was, with ORs for severely abnormal outcomes of 12.8 (1.31-124) and 21.6 (1.05-189), respectively. In multivariate analyses, aEEG and rcSO2 remained independently predictive in the model at 48 hours and significantly from 72 hours after birth onward. CONCLUSION: aEEG was a strong predictor of adverse outcome. After 48 hours of cooling, a higher rcSO2 was associated with a severely abnormal outcome, adding to the predictive value of aEEG in cooled, asphyxiated infants.

DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia.

We investigated the prognostic impact of minimal residual disease (MRD) monitoring in acute myeloid leukemia patients harboring DNA methyltransferase 3A-R882H/-R882C mutations (DNMT3Amut). MRD was determined by real-time quantitative PCR (RQ-PCR) in 1494 samples of 181 DNMT3Amut patients. At the time of diagnosis, DNMT3Amut transcript levels did not correlate with presenting clinical characteristics and concurrent gene mutations as well as the survival end points. In Cox regression analyses, bone marrow (BM) DNMT3Amut transcript levels (log10-transformed continuous variable) were not associated with the rate of relapse or death. DNMT3Amut transcript levels were significantly higher in BM than in blood after induction I (P=0.01), induction II (P=0.05), consolidation I (P=0.004) and consolidation II (P=0.008). With regard to the clinically relevant MRD time points, after two cycles of induction and at the end of therapy, DNMT3Amut transcript levels had no impact on the end point remission duration and overall survival. Of note, only a minority of the patients achieved RQ-PCR negativity, whereas most had constantly high DNMT3Amut transcript levels, a finding which is consistent with the persistence of clonal hematopoiesis in hematological remission.

Kidney Blow Out Due to Inguinal Herniation of the Ureter in an Infant.

Ureteroinguinal herniation is a rare event, usually diagnosed during the surgical repair of inguinal hernias. Here, we describe the first case of a kidney blow out due to this condition in a male infant.

Epidemiological, genetic, and clinical characterization by age of newly diagnosed acute myeloid leukemia based on an academic population-based registry study (AMLSG BiO).

We describe genetic and clinical characteristics of acute myeloid leukemia (AML) patients according to age from an academic population-based registry. Adult patients with newly diagnosed AML at 63 centers in Germany and Austria were followed within the AMLSG BiO registry (NCT01252485). Between January 1, 2012, and December 31, 2014, data of 3525 patients with AML (45% women) were collected. The median age was 65 years (range 18-94). The comparison of age-specific AML incidence rates with epidemiological cancer registries revealed excellent coverage in patients < 70 years old and good coverage up to the age of 80. The distribution according to the European LeukemiaNet (ELN) risk categorization from 2010 was 20% favorable, 31% intermediate-1, 28% intermediate-2, and 21% adverse. With increasing age, the relative but not the absolute prevalence of patients with ELN favorable and intermediate-1 risk (p < 0.001), with activating FLT3 mutations (p < 0.001), with ECOG performance status < 2 (p < 0.001), and with HCT-CI comorbidity index < 3 (p < 0.001) decreased. Regarding treatment, obesity and favorable risk were associated with an intensive treatment, whereas adverse risk, higher age, and comorbidity index > 0 were associated with non-intensive treatment or best supportive care. The AMLSG BiO registry provides reliable population-based distributions of genetic, clinical, and treatment characteristics according to age.

Design of the SALT Osteoporosis Study: a randomised pragmatic trial, to study a primary care screening and treatment program for the prevention of fractures in women aged 65 years or older.

BACKGROUND: Several drugs have become available for the treatment of osteoporosis. However, screening and treatment of patients with a high fracture risk is currently not recommended in the Netherlands, because the effectiveness of bone sparing drugs has not been demonstrated in the general primary care population. Here we describe the design of the SALT Osteoporosis study, which aims to examine whether the screening and treatment of older, female patients in primary care can reduce fractures, in comparison to usual care. METHODS: A randomised pragmatic trial has been designed using a stepwise approach in general care practices in the Netherlands. Women aged ≥65 years, who are not prescribed bone sparing drugs or corticosteroids are eligible for the study. First, women with at least one clinical risk factor for fractures, as determined by questionnaires, are randomly assigned to the intervention or control group. Second, women in the intervention group having a high fracture risk according to our screening program, including an adapted fracture risk assessment (FRAX) tool, combined with dual-energy x-ray absorptiometry (DXA), and instant vertebral assessment (IVA), are offered a structured treatment program. The women in the control group receive care as usual and will undergo the same screening as the intervention group at the end of the trial. The follow-up duration will be three years and the primary outcome is time to first incident fracture and the total number of fractures. DISCUSSION: The results of the current study will be very important for underpinnings of the prevention strategy of the osteoporosis guidelines. TRIAL REGISTRATION: ID NTR2430 . Registered 26 July 2010.

[Two-year follow-up of infants born at 24 weeks gestation; first outcomes following implementation of the new 'Guideline for perinatal policy in cases of extreme prematurity']. / Follow-up na 2 jaar van kinderen geboren bij 24 weken.

OBJECTIVE: Since 2010 the guideline 'Guideline for perinatal policy in cases of extreme prematurity' has advised an active policy in infants born at 24 weeks gestation. We investigated how infants born at 24 and 25 weeks gestation in the first year following the implementation of the guideline had developed by the age of 2 years. DESIGN: Retrospective national cohort study. METHOD: The study population consisted of all surviving infants born in the Netherlands at 24 or 25 weeks gestation in the period from 1 October 2010 to 1 October 2011. At a corrected age of 2 years the children underwent a general physical and neurological examination, and their cognitive scores were determined on the 'Bayley scales of infant and toddler development' (Bayley III). Examinations took place in the 10 neonatal intensive care units (NICU's) in the Netherlands. RESULTS: Of 185 extremely premature infants, 166 were admitted to a NICU. A total of 95 survived to a corrected age of 2 years; 78 (82%) children were examined. Their average cognitive score on the Bayley III scale was 88 (SD: 16). Among the children born at 24 weeks gestation, 20% had mild disabilities and 20% had moderate to severe disabilities. Among the children born at 25 weeks gestation, 17% had mild disabilities and 12% had moderate to severe disabilities. CONCLUSION: Of the children born at 24 weeks gestation in the first year after the introduction of active policy in the Netherlands and surviving to 2 years of age (46%), more than half had developed without disabilities. This was comparable to children born at 25 weeks gestation. Of all children born at 24 weeks gestation, 25% survived to 2 years of age without disabilities.

Condensed versus standard schedule of high-dose cytarabine consolidation therapy with pegfilgrastim growth factor support in acute myeloid leukemia.

The aim of this cohort study was to compare a condensed schedule of consolidation therapy with high-dose cytarabine on days 1, 2 and 3 (HDAC-123) with the HDAC schedule given on days 1, 3 and 5 (HDAC-135) as well as to evaluate the prophylactic use of pegfilgrastim after chemotherapy in younger patients with acute myeloid leukemia in first complete remission. One hundred and seventy-six patients were treated with HDAC-135 and 392 patients with HDAC-123 with prophylactic pegfilgrastim at days 10 and 8, respectively, in the AMLSG 07-04 and the German AML Intergroup protocol. Time from start to chemotherapy until hematologic recovery with white blood cells >1.0 G/l and neutrophils >0.5 G/l was in median 4 days shorter in patients receiving HDAC-123 compared with HDAC-135 (P<0.0001, each), and further reduced by 2 days (P<0.0001) by pegfilgrastim. Rates of infections were reduced by HDAC-123 (P<0.0001) and pegfilgrastim (P=0.002). Days in hospital and platelet transfusions were significantly reduced by HDAC-123 compared with HDAC-135. Survival was neither affected by HDAC-123 versus HDAC-135 nor by pegfilgrastim. In conclusion, consolidation therapy with HDAC-123 leads to faster hematologic recovery and less infections, platelet transfusions as well as days in hospital without affecting survival.