Serum carboxymethyllysine concentration is associated with erosive hand osteoarthritis.

OBJECTIVE: Carboxymethyllysine (CML) and homocitrulline (HCit) are the products of two non-enzymatic post-translational modifications of protein, a process related to age. We investigated whether serum CML and HCit concentrations were associated with hand osteoarthritis (HOA), especially erosive HOA. DESIGN: Serum CML and HCit were measured by using liquid chromatography coupled with tandem mass spectrometry at inclusion in 386 patients included in the DIGItal Cohort Design (DIGICOD) cohort. We investigated whether serum CML and/or HCit concentrations were associated with erosive HOA or with HOA clinical and radiological features. Moreover, we compared the tissular concentrations of CML and HCit in OA and non-OA cartilage from proximal interphalangeal and metacarpo-phalangeal (MCP) joints from human cadaveric donors. RESULTS: Median (IQR) serum CML concentration was lower in patients with erosive HOA than those with non-erosive HOA (178.7 [157.1-208.8] vs 194.7 [168.9-217.1] µmol/mol Lys, P = 0.002), but median HCit concentration did not differ between the groups (193.9 [162.9-232.0] vs 193.9 [155.9-224.6] µmol/mol Lys). Cartilage HCit and CML concentrations were not correlated with clinical features. Serum CML concentration was higher in OA than non-OA MCPs (7.0 vs 4.0 mmol/mol Lys, P = 0.01). CONCLUSIONS: Serum CML concentration was lower in erosive HOA than non-erosive HOA, and cartilage CML concentration was higher in OA than non-OA cartilage. These results encourage further studies to test whether serum CML could be a new prognostic biomarker in HOA.

Systematic use of short unicortical epiphyseal locking screws versus full-length unicortical locking screws in distal radius fracture volar plating: A prospective and comparative study.

PURPOSE: Volar locking plates, used in distal radius fracture (DRF), present a risk of injuring extensor tendons with screws penetrating the dorsal cortex of the radius. Actually, even when aiming to use maximum-length unicortical locking screws, some still could be bicortical. We hypothesize the use of only short unicortical screws would allow a proper stabilization of the radial epiphysis without the risk of dorsal cortex penetration. MATERIALS AND METHODS: A prospective monocentric non-randomized study was conducted. Patients with DRF (excepted for partial dorsal joint fractures) were treated in group A with short locking epiphyseal screws (16 mm for females, 18 mm for males) and in group B with full-length unicortical locking screws. Ultrasound was done 3 months postoperatively to evaluate the number and length of prominent dorsal screws. X-rays were performed after 6 weeks to assess stability according to volar tilt and radial inclination variations. RESULTS: There were 37 patients in group A and 39 in group B with 148 and 156 epiphyseal screws, respectively. In group A, there were 0% of dorsal penetrating screws against 6.5% (10 screws from 8 patients) in group B (p < 0.05). There was no significant difference for the stability between the groups: mean volar tilt variation ( - 0.6° vs. - 0.7°) and mean radial inclination variation ( - 0.4° vs. - 0.4°). CONCLUSION: For a same stability with volar locking plates for DRF, short epiphyseal locking screws should be preferred to full-length unicortical screws in order to prevent extensor tendon injuries. Based on 75% of distal radial average anteroposterior width for each sex, screw lengths of 16 mm for females and 18 mm for males seem to be the length to use. LEVEL OF EVIDENCE 2: Prospective, Comparisons made, non-randomized.

[The wrapping induced membrane technique for treating recalcitrant non unions]. / La technique de la membrane induite « engainante ¼ pour le traitement des pseudarthroses rebelles sans perte de substance osseuse et le renforcement des reconstructions osseuses segmentaires fragiles. Rapport préliminaire.

The induced membrane technique is now well accepted for reconstruction of segmental bone defect. On the other hand, some cases of aseptic non-union are unsuccessfully treated by several surgical attempts for obtaining bone healing. The two stages wrapping induced membrane technique was developed initially for treating atrophic and recalcitrant aseptic non union without bone loss. At the first stage, the site of non-union was firmly fixed and tiles of cement were placed close to the bone on two or three aspects of the bone. At the second stage, after removing the spacers, the induced cavities were filled with cancellous bone autograft. In the two reported cases bone healing was acquired in 4 months. One case was a recalcitrant atrophic non-union of the humeral shaft, the other case concerned the enhancement of an insufficient segmental reconstruction of the femur. The follow up were respectively 3 years and 2 years without complication. The membrane induced by the cement tiles prevents the bone graft resorption and improves the osteogenicity through its biological properties.

Scoring of tumor-infiltrating lymphocytes: From visual estimation to machine learning.

The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden and other biomarkers, has been demonstrated to be a marker of response to immune-checkpoint therapy in several cancers. Pathologists have therefore started to devise standardized visual approaches to quantify TILs for therapy prediction. However, despite successful standardization efforts visual TIL estimation is slow, with limited precision and lacks the ability to evaluate more complex properties such as TIL distribution patterns. Therefore, computational image analysis approaches are needed to provide standardized and efficient TIL quantification. Here, we discuss different automated TIL scoring approaches ranging from classical image segmentation, where cell boundaries are identified and the resulting objects classified according to shape properties, to machine learning-based approaches that directly classify cells without segmentation but rely on large amounts of training data. In contrast to conventional machine learning (ML) approaches that are often criticized for their "black-box" characteristics, we also discuss explainable machine learning. Such approaches render ML results interpretable and explain the computational decision-making process through high-resolution heatmaps that highlight TILs and cancer cells and therefore allow for quantification and plausibility checks in biomedical research and diagnostics.

[Pharmacotherapy of chronic neuropathic pain]. / Pharmakologische Therapie chronischer neuropathischer Schmerzen.

Chronic neuropathic pain has a prevalence of 6.9-10% in the general population. The current recommendations for treatment are presented based on a literature search. Neuropathic pain requires the use of co-analgesic, antidepressant, anticonvulsant drugs and topical agents because non-opioid analgesic drugs are usually ineffective. The use of meta-analyses tricyclic antidepressants, selective serotonin-norephinephrine reuptake inhibitors, and calcium channel anticonvulsants are recommended as the drugs of first choice. Under certain conditions chronic neuropathic pain can be treated with opioids. Topical therapeutics are only used to treat peripheral neuropathic pain. At present the use of drugs is independent of the etiology of the pain. Comorbidities, concomitant medication, potential side effects and patients' age have to be considered in treatment planning.

[The fascio-cutaneous fibular island flap]. / Le lambeau fasciocutané fibulaire en ilôt.

The perforators of the fibular artery provide a well vascularised supra fascial network which allows to raise a proximally or a distally based island fascio cutaneous flap with an adipo-fascial pedicle. We present a short series of five cases of this flap for coverage of soft tissue defects involving the region of the knee, the distal third of the leg and the lateral aspect of the heel. All flaps healed entirely without venous congestion. The advantages of the fascio cutaneous fibular island flap are the supine operative position, the preservation of the sural nerve and the lesser saphenous vein and a pivot point which can be located at the middle third of the leg. According to our experience, the fascio cutaneous fibular island flap is especially indicated for repairing defects of the distal leg.

[Reembursing health-care service provider networks]. / Vergütungsstrukturen von Versorgungsnetzwerken.

Health-care service provider networks are regarded as an important instrument to overcome the widely criticised fragmentation and sectoral partition of the German health-care system. The first part of this paper incorporates health-care service provider networks in the field of health-care research. The system theoretical model and basic functions of health-care research are used for this purpose. Furthermore already established areas of health-care research with strong relations to health-care service provider networks are listed. The second part of this paper introduces some innovative options for reimbursing health-care service provider networks which can be regarded as some results of network-oriented health-care research. The origins are virtual budgets currently used in part to reimburse integrated care according to §§ 140a ff. SGB V. Describing and evaluating this model leads to real budgets (capitation) - a reimbursement scheme repeatedly demanded by SVR-Gesundheit (German governmental health-care advisory board), for example, however barely implemented. As a final step a direct reimbursement of networks by the German sickness fund is discussed. Advantages and challenges are shown. The development of the different reimbursement schemes is partially based on models from the USA.

[Findings in uteri and ovaries from Eringer cows slaughtered due to fertility problems]. / Befunde von Uterus und Ovarien geschlacbteter Eringerkühe mit Fruchtbarkeitsproblemen.

Eringer cows are often slaughtered due to fertility problems which result from inflammatory and degenerative changes of the uterus or hormonal imbalances. Twenty-one genital tracts from Eringer cows suffering from fertility problems were collected in the abattoir. The purpose of the study was the macroscopic evaluation of the ovaries and the uterus followed by a histological and microbiological analysis of the uterus. Data from inseminations and calvings were provided by the Eringer breeding association and through the internet portal www.agate.ch. Median age of the cows was 6.9 years, number of calves per cow was 2.5 and median period between last calving and slaughter was 1.5 years. In 13 from 21 of the urogenital tracts examined, macroscopic abnormalities of the ovaries and/or histologic or microbiologic findings in the uterus could explain fertility-associated slaughter.

Growth behavior and mRNA expression profiling during growth of IPEC-J2 cells.

OBJECTIVE: The IPEC-J2 cell line is used as an in vitro small intestine model for swine, but it is also used as a model for the human intestine, presenting a relatively unique setting. By combining electric cell-substrate impedance sensing, with next-generation-sequencing technology, we showed that mRNA gene expression profiles and related pathways can depend on the growth phase of IPEC-J2 cells. Our investigative approach welcomes scientists to reproduce or modify our protocols and endorses putting their gene expression data in the context of the respective growth phase of the cells. RESULTS: Three time points are presented: (TP1) 1 h after medium change (= 6 h after seeding of cells), (TP2) the time point of the first derivative maximum of the cell growth curve, and a third point at the beginning of the plateau phase (TP3). Significantly outstanding at TP1 compared to TP2 was upregulated PLEKHN1, further FOSB and DEGS2 were significantly downregulated at TP2 compared to TP3. Any provided data can be used to improve next-generation experiments with IPEC-J2 cells.

The descending pain modulation system predicts short term efficacy of multimodal pain therapy: an observational prospective cohort study.

OBJECTIVES: Treating chronic pain patients with multimodal pain therapy (MMPT) alters perception, awareness, and processing of pain at multiple therapeutic levels. Several clinical observations suggest that the effects of therapy may go beyond the possible sum of each level of therapy and may be due to a central descending inhibitory effect measurable by conditioned pain modulation (CPM). Thus, we investigated whether CPM is able to identify a group of patients that benefit particularly from MMPT. METHODS: This was an observational prospective cohort study. Patients were hospitalized on a special pain medicine ward with specially trained staff for 10 days. The patients were questioned and had investigations before and shortly after MMPT and were followed-up on 3 months post discharge. Before and after treatment, subjects were investigated via CPM and quantitative sensory testing (QST) as well as completing questionnaires. The study was registered in the German Clinical Trials Register (DRKS00006850). RESULTS: During the study period of 24 months, 224 chronic pain patients were recruited. 51 percent of patients completed the study period. There was an improvement in overall groups regarding all domains assessed, lasting beyond the end of the intervention. Patients with a sufficient CPM effect, defined as a reduction in pain during the conditioning stimulus, at baseline did show a more pronounced reduction in mean pain ratings than those without. This was not the case 3 months after therapy. Furthermore, sufficient CPM was identified as a predictor for pain reduction using a linear regression model. CONCLUSION: In conclusion, this study shows that while a heterogeneous group of patients with chronic pain disorders does sustainably benefit from MMPT in general, patients with a sufficient CPM effect do show a more pronounced decrease in pain ratings directly after therapy in comparison to those without.

Pain at one body site can be reduced, when another painful stimulus occurs at the same time. This mechanism is referred to as conditioned pain modulation (CPM).Some patients with chronic pain are treated using different methods such as medication, physiotherapy, and patient education in an in-patient setting, referred to as multimodal pain therapy (MMST). To improve pain therapy, it is vital to identify whether patients who respond especially well to a certain treatment show specific characteristics (i.e. mechanism-based therapy). We investigated whether the prospect of success of MMST is related to how well CPM works in patients. We assessed the CPM effect and sensory function of 224 patients with chronic pain before and after therapy to answer this question. Additionally, patients completed questionnaires about their pain, mood, quality of life, and sleep directly after therapy and three months later. All patients showed improvement after therapy, but in those in which CPM worked well, pain was reduced stronger than in those in which CPM did not. Three months after treatment, the difference disappeared.

Palliative surgery for thumb involvement in ulnar paralysis.

Ulnar paralysis has multiple clinical presentations, which are due to partial recovery or to anatomical variations between the ulnar and median nerves. The main sequelae of ulnar nerve paralysis are the loss of hand strength with impairment of all intrinsic functions of the fingers and some of the thumb's functions. Weakness of the adductor pollicis and flexor pollicis brevis muscles may manifest as weak key pinch with automatic flexion of the thumb interphalangeal joint when gripping. Indications for palliative surgery have decreased due to advances in peripheral nerve surgery. However, palliative surgery still has a significant role to play when nerve repair techniques are not indicated or do not provide satisfactory results. The principle is to reinforce metacarpophalangeal flexion while stabilizing the thumb's interphalangeal joint, thus supplementing the action of the flexor pollicis brevis. This is generally done by transferring the flexor digitorum superficialis tendon of the fourth finger to the distal insertion of the superficial thenar muscles and the extensor pollicis longus. Restoration of the first dorsal interosseous is more rarely indicated.

Tendon transfers to restore elbow flexion.

Elbow flexion paralysis is one of most significant deficiencies in the upper limb. When secondary to brachial plexus palsy or nerve trunk lesions, restoration of elbow flexion by means of early nerve surgery or palliative transfers should be part of a comprehensive treatment plan. Tendon transfers are indicated in long-standing palsies, in those who are poor candidates for nerve surgery or when the results of nerve surgery are inadequate. A regional pedicled muscle transfer is performed if available. In this case, a "strong" donor is preferred (pectoralis major with pectoralis minor transfer, triceps brachii to biceps brachii transfer, or bipolar latissimus dorsi transfer). A "weak" transfer is indicated in patients who have incomplete recovery of elbow flexion (MRC 2 strength): isolated pectoralis minor transfer, medial epicondylar muscle transfer according to Steindler technique, or advancement of biceps brachii tendon on forearm. When no donor muscle is available, a free reinnervated muscle transfer may be indicated if age and nerve regeneration conditions are favorable.

Treatment of congenital syndactyly.

Defined as the union of two adjacent digits, syndactyly is one of the most common congenital deformities. The severity of the malformation depends on the fusion level, the tissues involved in the union, and whether it is isolated or syndromic. In order to improve the hand's appearance and function, surgery is recommended in the great majority of cases, ideally during early childhood (i.e., before entering school). Web space reconstruction is done using local flaps. Depending on the flap design, digital resurfacing can be done with or without skin grafts. While graftless techniques have shorter operating times and no morbidity associated with skin harvesting, their cosmetic outcomes seem to be worse than those of traditional grafting techniques, with more postoperative complications; furthermore, such techniques cannot be used in all cases, especially those with osteoarticular fusions. When the fingertip is involved, paronychial reconstruction is carried out with pulp flaps. The prognosis for these deformities directly depends on their severity, with excellent outcomes in cases of cutaneous fusion, and much less predictable ones when osteoarticular and/or tendinous tissues are involved.

Chondrodesis of the wrist in children with severe paralytic hand deformities.

We examined the anatomical and clinical results of a new wrist subphyseal arthrodesis method called chondrodesis, which relies on resorbable suture-bone fixation for children with severe paralytic hand deformities and does not require fixation devices or bone grafting. Four children's wrists underwent the procedure, resulting in three successful wrist bone fusions. The wrists were stabilized by joint fusion in 4-5 months in good positions, ranging from neutral to extension 15°, while still allowing the forearm to keep growing since the radial growth plate remained open as of the last follow-up. The procedure improved hand function (House score, Raimondi score) and appearance. It also increased control over gripping motions with the operated hand, and even restored key pinch ability in one of the patients. The youngest patient was not able to achieve bone fusion at the key sites and will need further corrective procedures at a later and more optimal age. This novel procedure is appealing because of its technical reproducibility, low cost, encouraging outcomes, ease of rehabilitation, and because it spares the physeal cartilage.

Psychological burden, stressors and resources of social workers working with women and children who suffered extreme violence by the 'Islamic state': A mixed method study.

OBJECTIVE: This explorative study aimed to determine the extent of psychological burden in social workers working with traumatized refugees. In addition, distressing and helpful factors determining the psychosocial burden were to be identified and described. METHODS: Cross-sectional, mixed method design using quantitative and qualitative methods. The quantitative part included the Perceived Stress Questionnaire (PSQ) and items to assess specific factors of the working-context. The qualitative part is based on 5 focus groupdiscussions and 16 individual interviews. Evaluation was carried out using qualitative content analysis (QCA) including cross-analysis along the subscales of the PSQ to organise the qualitative material. RESULTS: N = 54 social workers completed the questionnaire. High scores were found for all subscales of the PSQ. The distressing factor rated the highest was need of interpreters to communicate (M = 5.1, SD = 1.71), the helpful factor rated the highest was communication skills (M = 6.35, SD = 0.73). In the QCA, aspects of distressing and helpful factors were identified and further detailed. CONCLUSION: According to the here presented study results, the psychological burdens of social workers working with refugees seem to be high. The impact of distressing factors such as working with interpreters and exposure to trauma content or PTSD symptoms might be reduced by offering specific education and supervision. The individual extent of psychological burden should be considered and (re-)evaluated on a regular basis as secondary prevention. Helpful factors like self-care, teamwork, networking and cooperation are evident and should be supported by implementing professional and psychological support.

Lunar Prospector: overview.

Lunar Prospector is providing a global map of the composition of the moon and analyzing the moon's gravity and magnetic fields. It has been in a polar orbit around the moon since 16 January 1998. Neutron flux data show that there is abundant H, and hence probably abundant water ice, in the lunar polar regions. Gamma-ray and neutron data reveal the distribution of Fe, Ti, and other major and trace elements on the moon. The data delineate the global distributions of a key trace element-rich component of lunar materials called KREEP and of the major rock types. Magnetic mapping shows that the lunar magnetic fields are strong antipodal to Mare Imbrium and Mare Serenitatis and has discovered the smallest known magnetosphere, magnetosheath, and bow shock complex in the solar system. Gravity mapping has delineated seven new gravity anomalies and shown that the moon has a small Fe-rich core of about 300 km radius.

Martian craters: comparison of statistical counts.

Comparisons of the various crater counts obtained from the Mariner IV photographs indicate that, out of 300 to 600 possible craters mapped by different investigators, only about 120 craters can be reliably identified. Thus, only a lower limit for the Martian crater density can be established from the Mariner IV data.

Mariner IV: Analysis of Preliminary Photographs.

Comparison of the distributions of Martian and lunar crater diameters indicates that the visible surface of Mars is 2.2 to 3 x 10(9) years old. This result implies that in the early history of Mars large-scale subaerial erosion occurred. Of 69 Martian craters with diameters greater than 10 kilometers, 13 percent have central peaks. This compares favorably with the frequency (11.7 percent) of central peaks among lunar craters and may indicate that the central peaks are a direct result of the impact mechanism rather than post-impact volcanism. A well-defined system of lineaments is shown in the Mariner photographs. The presence of these lineaments may indicate that Mars has lost appreciable angular momentum during its history.