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.

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.

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 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.

[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.

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.

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.

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.

Does environmental stress affect cortisol biodistribution in freshwater mussels?

As of today, regulation and physiological purpose of steroid hormones in invertebrates such as mussels are not completely understood. Many studies were able to show their presence, but their origin and genesis are not clear. Nevertheless, knowledge about changes in steroid hormone biodistribution in reaction to treatments could improve our understanding of their physiological functions in these species. Cortisol is a corticosteroid, which is frequently used as a stress biomarker in vertebrates, like fish or higher organisms. The aim of the study was to optimize cortisol extraction from various tissues of mussels, to develop a quantitative ELISA test system, and to study changes in biodistribution of cortisol in reaction to negative and positive stimulation treatments. As model organism, we used Anodonta anatina, a widespread freshwater mussel species native to Europe. We quantified cortisol concentrations in hepatopancreas, mantle, gills, gonads and the foot muscle. Tissue-specific reactions to environmental influences, simulated with the chemical stressors copper (II) chloride and sodium chloride, were assessed. During the 24-hours treatment, we additionally observed changes in cortisol regulation in response to feeding activity of the mussels. Besides, we found highly significant variations in the biodistribution of cortisol in different tissues, with a peak in the hepatopancreas. Whole body cortisol did not increase in the treated groups. However, balancing of all measured tissues showed redistribution of more than 10% of total body cortisol from the hepatopancreas to all other tissues during copper (II) chloride stressor treatment, but also when mussels ingested feed, compared to the non-fed control group. No redistribution was observed during sodium chloride treatment. We conclude that there can be a redistribution of cortisol in mussels, depending on external influences.

[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.

Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: One-year interim results of SPACE-2.

BACKGROUND: Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. METHODS: SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. FINDINGS: It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. INTERPRETATION: The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.

Surgical strategy in extensive proximal brachial plexus palsies.

PURPOSE: To describe and assess an overall surgical strategy addressing extensive proximal brachial plexus injuries (BPI). METHODS: Forty-five consecutive patients' charts with C5-C6-C7 and C5-C6-C7-C8 BPI were reviewed. Primary procedures were nerve transfers to restore elbow function and grafts to restore shoulder function when a cervical root was available; when nerve surgery was not possible or had failed, tendon transfers were conducted at the elbow while addressing shoulder function with glenohumeral arthrodesis or humeral osteotomy. Tendon transfers were used to restore finger extension. RESULTS: Forty-one patients underwent elbow flexion reanimation: thirty-eight had nerve transfers and eight received tendon transfers, including five cases secondary to nerve surgery failure; grade-3 strength or greater was reached in thirty-seven cases (90%). Twenty-nine patients had nerve transfers to restore elbow extension: twenty-five recovered grade-3 or grade-4 strength (86%). Forty-one patients underwent shoulder surgery: fourteen had nerve surgery and thirty-one received palliative procedures, including four cases secondary to nerve surgery failure; thirty patients recovered at least 60° of abduction and rotation (73%). Distal reconstruction was performed in thirty-seven patients, providing finger full extension in all cases but two (95%). CONCLUSIONS: A standardized strategy may be used in extensive proximal BPI, providing overall satisfactory outcomes.

Transfer of the triceps brachii to the finger and thumb extensors: Anatomical study and report on one case.

Our aims were to study the anatomical feasibility of triceps brachii long head (TBLH) transfer to the extensor digitorum communis (EDC) and extensor pollicis longus (EPL) tendons through a medial route, and to report on its first clinical application. Dissections were conducted on 10 fresh-frozen cadaver specimens. Using a posteromedial approach, the TBLH was separated from the remaining triceps and extended distally with a fascia lata strip. This strip was then tunneled through a medial route and secured distally to the EDC and EPL tendons. The transfer tenodesis effect during elbow extension was assessed with metacarpophalangeal (MCP) joint motion of the thumb and index finger, and the distance between the thumb and index finger tips (TI distance). This transfer was performed in an eight-year-old boy with incomplete recovery of a right brachial plexus birth palsy; preoperatively, shoulder and elbow functions were recovered as well as active gripping distally, but he had no active wrist or finger extension. With the trapeziometacarpal and radiocarpal joints stabilized, 90° elbow extension provided a mean extension of the thumb and index finger MCP joints of 34 ± 5° and 90 ± 11°, respectively, with a mean TI distance of 116 ± 16 mm. Twelve months after surgery, the boy had full active MCP joint extension, independent from elbow extension. Transferring the TBLH to the EDC and EPL tendons is anatomically feasible. Larger clinical studies will be needed to assess more adequately its functional outcomes.

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.

[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.

Impact of suggestion on the human experimental model of cold hyperalgesia after topical application of high-concentration menthol [40%].

BACKGROUND: Human experimental pain models in healthy subjects offer unique possibilities to study mechanisms of pain within a defined setting of expected pain symptoms, signs and mechanisms. Previous trials in healthy subjects demonstrated that topical application of 40% menthol is suitable to induce cold hyperalgesia. The objective of this study was to evaluate the impact of suggestion on this experimental human pain model. METHODS: The study was performed within a single-centre, randomized, placebo-controlled, double-blind, two-period crossover trial in a cohort of 16 healthy subjects. Subjects were tested twice after topical menthol application (40% dissolved in ethanol) and twice after ethanol (as placebo) application. In the style of a balanced placebo trial design, the subjects received during half of the testing the correct information about the applied substance (topical menthol or ethanol) and during half of the testing the incorrect information, leading to four tested conditions (treatment conditions: menthol-told-menthol and menthol-told-ethanol; placebo conditions: ethanol-told-menthol and ethanol-told-ethanol). RESULTS: Cold but not mechanical hyperalgesia was reliably induced by the model. The cold pain threshold decreased in both treatment conditions regardless whether true or false information was given. Minor suggestion effects were found in subjects with prior ethanol application. CONCLUSIONS: The menthol model is a reliable, nonsuggestible model to induce cold hyperalgesia. Mechanical hyperalgesia is not as reliable to induce. SIGNIFICANCE: Cold hyperalgesia may be investigated under unbiased and suggestion-free conditions using the menthol model of pain.