Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration.

During both embryonic development and adult tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. A thorough understanding of how stem cells in the skeleton interpret mechanical stimuli and enact regeneration would shed light on how forces are transduced to the nucleus in regenerative processes. Here we develop a genetically dissectible mouse model of mandibular distraction osteogenesis-which is a process that is used in humans to correct an undersized lower jaw that involves surgically separating the jaw bone, which elicits new bone growth in the gap. We use this model to show that regions of newly formed bone are clonally derived from stem cells that reside in the skeleton. Using chromatin and transcriptional profiling, we show that these stem-cell populations gain activity within the focal adhesion kinase (FAK) signalling pathway, and that inhibiting FAK abolishes new bone formation. Mechanotransduction via FAK in skeletal stem cells during distraction activates a gene-regulatory program and retrotransposons that are normally active in primitive neural crest cells, from which skeletal stem cells arise during development. This reversion to a developmental state underlies the robust tissue growth that facilitates stem-cell-based regeneration of adult skeletal tissue.

Causes of Industrial Protein A Column Degradation, Explored Using Raman Spectroscopy.

Monoclonal antibodies (mAbs) are used extensively as biotherapeutics for chronic and acute conditions. Production of mAbs is lengthy and expensive, with protein A affinity capture the most costly step, due both to the nature of the resin and its marked reduction in binding capacity with repeated use. Our previous studies using in situ ATR-FTIR spectroscopy indicated that loss in protein A binding capacity is not the result of leaching or degradation of protein A ligand, suggesting fouling is the principal cause. Here we explore binding behavior and resin capacity loss using Raman spectroscopy. Our data reveal a distinct Raman spectral fingerprint for mAb bound to the protein A ligand of MabSelect SuRe. The results show that the drop in static binding capacity (SBC) previously observed for used protein A resin is discernible by Raman spectroscopy in combination with partial least-squares regression. The SBC is lowest (35.76 mg mL-1) for used inlet resin compared to used outlet (40.17 mg mL-1) and unused resin samples (70.35 mg mL-1). Depth profiling by Raman spectroscopy indicates that at below saturating concentrations (∼18 mg mL-1), binding of mAb is not homogeneous through used resin beads with protein binding preferentially to the outer regions of the bead, in contrast to fully homogeneous distribution through unused control MabSelect SuRe resin beads. Analysis of the Raman spectra indicates that one foulant is irreversibly bound mAb. The presence of irreversibly bound mAb and host cell proteins was confirmed by mass spectrometric analysis of used resin beads.

Wounds Inhibit Tumor Growth In Vivo.

OBJECTIVE: The aim of this study was to determine the interaction of full thickness excisional wounds and tumors in vivo. SUMMARY OF BACKGROUND DATA: Tumors have been described as wounds that do not heal due to similarities in stromal composition. On the basis of observations of slowed tumor growth after ulceration, we hypothesized that full thickness excisional wounds would inhibit tumor progression in vivo. METHODS: To determine the interaction of tumors and wounds, we developed a tumor xenograft/allograft (human head and neck squamous cell carcinoma SAS/mouse breast carcinoma 4T1) wound mouse model. We examined tumor growth with varying temporospatial placement of tumors and wounds or ischemic flap. In addition, we developed a tumor/wound parabiosis model to understand the ability of tumors and wounds to recruit circulating progenitor cells. RESULTS: Tumor growth inhibition by full thickness excisional wounds was dose-dependent, maintained by sequential wounding, and relative to distance. This effect was recapitulated by placement of an ischemic flap directly adjacent to a xenograft tumor. Using a parabiosis model, we demonstrated that a healing wound was able to recruit significantly more circulating progenitor cells than a growing tumor. Tumor inhibition by wound was unaffected by presence of an immune response in an immunocompetent model using a mammary carcinoma. Utilizing functional proteomics, we identified 100 proteins differentially expressed in tumors and wounds. CONCLUSION: Full thickness excisional wounds have the ability to inhibit tumor growth in vivo. Further research may provide an exact mechanism for this remarkable finding and new advances in wound healing and tumor biology.

Insight into purification of monoclonal antibodies in industrial columns via studies of Protein A binding capacity by in situ ATR-FTIR spectroscopy.

Therapeutic monoclonal antibodies (mAbs) are effective treatments for a range of cancers and other serious diseases, however mAb treatments cost on average ∼$100 000 per year per patient, limiting their use. Currently, industry favours Protein A affinity chromatography (PrAc) as the key step in downstream processing of mAbs. This step, although highly efficient, represents a significant mAb production cost. Fouling of the Protein A column and Protein A ligand leaching contribute to the cost of mAb production by shortening the life span of the resin. In this study, we assessed the performance of used PrAc resin recovered from the middle inlet, center and outlet as well as the side inlet of a pilot-scale industrial column. We used a combination of static binding capacity (SBC) analysis and Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy to explore the used resin samples. SBC analysis demonstrated that resin from the inlet of the column had lower binding capacity than resin from the column outlet. ATR-FTIR spectroscopy with PLS (partial least square) analysis confirmed the results obtained from SBC analysis. Importantly, in situ ATR-FTIR spectroscopy also allowed both measurement of the concentration and assessment of the conformational state of the bound Protein A. Our results reveal that PrAc resin degradation after use is dependent on column location and that neither Protein A ligand leaching nor denaturation are responsible for binding capacity loss.

Doxycycline Reduces Scar Thickness and Improves Collagen Architecture.

OBJECTIVE: To investigate the effects of local doxycycline administration on skin scarring. BACKGROUND: Skin scarring represents a major source of morbidity for surgical patients. Doxycycline, a tetracycline antibiotic with off-target effects on the extracellular matrix, has demonstrated antifibrotic effects in multiple organs. However, doxycycline's potential effects on skin scarring have not been explored in vivo. METHODS: Female C57BL/6J mice underwent dorsal wounding following an established splinted excisional skin wounding model. Doxycycline was administered by local injection into the wound base following injury. Wounds were harvested upon complete wound closure (postoperative day 15) for histological examination and biomechanical testing of scar tissue. RESULTS: A one-time dose of 3.90 mM doxycycline (2 mg/mL) within 12 hours of injury was found to significantly reduce scar thickness by 24.8% (P < 0.0001) without compromising tensile strength. The same effect could not be achieved by oral dosing. In doxycycline-treated scar matrices, collagen I content was significantly reduced (P = 0.0317) and fibers were favorably arranged with significantly increased fiber randomness (P = 0.0115). Common culprits of altered wound healing mechanics, including angiogenesis and inflammation, were not impacted by doxycycline treatment. However, engrailed1 profibrotic fibroblasts, responsible for scar extracellular matrix deposition, were significantly reduced with doxycycline treatment (P = 0.0005). CONCLUSIONS: Due to the substantial improvement in skin scarring and well-established clinical safety profile, locally administered doxycycline represents a promising vulnerary agent. As such, we favor rapid translation to human patients as an antiscarring therapy.

Activity interventions to improve the experience of care in hospital for people living with dementia: a systematic review.

BACKGROUND: An increasingly high number of patients admitted to hospital have dementia. Hospital environments can be particularly confusing and challenging for people living with dementia (Plwd) impacting their wellbeing and the ability to optimize their care. Improving the experience of care in hospital has been recognized as a priority, and non-pharmacological interventions including activity interventions have been associated with improved wellbeing and behavioral outcomes for Plwd in other settings. This systematic review aimed at evaluating the effectiveness of activity interventions to improve experience of care for Plwd in hospital. METHODS: Systematic searches were conducted in 16 electronic databases up to October 2019. Reference lists of included studies and forward citation searching were also conducted. Quantitative studies reporting comparative data for activity interventions delivered to Plwd aiming to improve their experience of care in hospital were included. Screening for inclusion, data extraction and quality appraisal were performed independently by two reviewers with discrepancies resolved by discussion with a third where necessary. Standardized mean differences (SMDs) were calculated where possible to support narrative statements and aid interpretation. RESULTS: Six studies met the inclusion criteria (one randomized and five non-randomized uncontrolled studies) including 216 Plwd. Activity interventions evaluated music, art, social, psychotherapeutic, and combinations of tailored activities in relation to wellbeing outcomes. Although studies were generally underpowered, findings indicated beneficial effects of activity interventions with improved mood and engagement of Plwd while in hospital, and reduced levels of responsive behaviors. Calculated SMDs ranged from very small to large but were mostly statistically non-significant. CONCLUSIONS: The small number of identified studies indicate that activity-based interventions implemented in hospitals may be effective in improving aspects of the care experience for Plwd. Larger well-conducted studies are needed to fully evaluate the potential of this type of non-pharmacological intervention to improve experience of care in hospital settings, and whether any benefits extend to staff wellbeing and the wider ward environment.

Wound healing and fibrosis: current stem cell therapies.

Scarring is a result of the wound healing response and causes tissue dysfunction after injury. This process is readily evident in the skin, but also occurs internally across organ systems in the form of fibrosis. Stem cells are crucial to the innate tissue healing response and, as such, present a possible modality to therapeutically promote regenerative healing while minimizing scaring. In this review, the cellular basis of scaring and fibrosis is examined. Current stem cell therapies under exploration for skin wound healing and internal organ fibrosis are discussed. While most therapeutic approaches rely on the direct application of progenitor-type cells to injured tissue to promote healing, novel strategies to manipulate the scarring response are also presented. As our understanding of developmental and stem cell biology continues to increase, therapies to encourage regeneration of healthy functional tissue after damage secondary to injury or disease will continue to expand.

Diagnostic Utilization and Accuracy of Pediatric Appendicitis Imaging at Adult and Pediatric Centers.

BACKGROUND: Diagnostic imaging in pediatric appendicitis may decrease rates of negative appendectomy and identify alternate pathologies. We compared imaging practices for children transferred from nonpediatric facilities versus directly admitted to our tertiary children's hospital for laparoscopic appendectomy, and assessed the diagnostic accuracy in each population based on final pathologic diagnosis. MATERIALS AND METHODS: After institutional review board approval, all cases of laparoscopic appendectomy at our children's hospital during 2015 were reviewed. Demographic and clinical data were collected, including age, transfer status, imaging studies, and pathologic diagnosis. Imaging practices in patients transferred from adult centers were compared with those directly admitted. RESULTS: There were 1153 included patients who underwent laparoscopic appendectomy for acute appendicitis during the study period, with 242 (20.9%) presenting as transfers from nonpediatric facilities. Of these, 73.5% underwent preoperative computed tomography (CT), compared with 26.4% of nontransfer patients (P < 0.000). All remaining patients received ultrasound (US). Despite variation in imaging strategies, rates of negative appendectomy were similar in transfer and nontransfer groups (1.7% versus 2.0%, respectively, P = 0.744). There were marginal differences in sensitivity of US and CT to detect appendix features between the transferring and referral centers. CONCLUSIONS: Our results show that nonpediatric facilities use CT more frequently to diagnose pediatric appendicitis. Rates of nontherapeutic surgery were equivalent between transferred and directly admitted patients, which is likely related to high performance of both imaging strategies. Transferring centers should strive to rely more heavily on US, which may require education and development of improved pediatric US capacity.

Clinical and Imaging Correlates of Pediatric Mucosal Appendicitis.

BACKGROUND: Mucosal appendicitis is a controversial entity that is histologically distinct from transmural appendicitis. There is mixed opinion regarding mucosal inflammation as a spectrum of appendicitis versus a negative appendectomy. The ability to distinguish these diagnoses preoperatively is of importance to prevent unnecessary surgery. We hypothesize that patients with mucosal appendicitis can be discriminated from those with transmural disease based on specific preoperative clinical and imaging findings. MATERIALS AND METHODS: After IRB approval, all patients who underwent laparoscopic appendectomy at our institution during 2015 were reviewed in the electronic medical record. Patients with mucosal appendicitis were identified and matched 2:1 to a random cohort of nonperforated transmural appendicitis cases. Demographic and clinical data were collected, including history, examination, laboratory, and imaging findings. Preoperative factors associated with mucosal appendicitis were modeled using binomial logistic regression analysis. RESULTS: Of 1153 appendectomies performed during 2015, 103 patients had pathologic diagnosis of mucosal appendicitis. When compared with patients with mucosal infection, leukocytosis >10,000 per microliter led to 5.9 times higher likelihood of transmural pathology (P = 0.000). Noncompressibility on ultrasound was associated with 7.3 times higher likelihood of transmural disease (P = 0.015). Echogenic changes were predictive of transmural appendicitis, conferring 3.9 times the risk (P = 0.007). Presence of free fluid led to 2.3 times the rate of transmural pathology (P = 0.007). Finally, for every millimeter decrease in appendiceal diameter, patients were half as likely to exhibit transmural disease (P = 0.000). Together, these variables can successfully predict presence of mucosal appendicitis on final pathology report at a rate of 82.1%, and explain 60% of the variance in diagnosis of mucosal versus transmural appendicitis (P = 0.000). CONCLUSIONS: Mucosal appendicitis remains a controversial pathologic entity, but is not associated with greater complications compared with transmural appendicitis when treated with laparoscopic appendectomy. Transmural disease can be predicted by leukocytosis, noncompressible appendix, presence of free fluid, larger appendiceal diameter and echogenicity.

Refining a model of collaborative care for people with a diagnosis of bipolar, schizophrenia or other psychoses in England: a qualitative formative evaluation.

BACKGROUND: Many people diagnosed with schizophrenia, bipolar or other psychoses in England receive the majority of their healthcare from primary care. Primary care practitioners may not be well equipped to meet their needs and there is often poor communication with secondary care. Collaborative care is a promising alternative model but has not been trialled specifically with this service user group in England. Collaborative care for other mental health conditions has not been widely implemented despite evidence of its effectiveness. We carried out a formative evaluation of the PARTNERS model of collaborative care, with the aim of establishing barriers and facilitators to delivery, identifying implementation support requirements and testing the initial programme theory. METHODS: The PARTNERS intervention was delivered on a small scale in three sites. Qualitative data was collected from primary and secondary care practitioners, service users and family carers, using semi-structured interviews, session recordings and tape-assisted recall. Deductive and inductive thematic analysis was carried out; themes were compared to the programme theory and used to inform an implementation support strategy. RESULTS: Key components of the intervention that were not consistently delivered as intended were: interaction with primary care teams, the use of coaching, and supervision. Barriers and facilitators identified were related to service commitment, care partner skills, supervisor understanding and service user motivation. An implementation support strategy was developed, with researcher facilitation of communication and supervision and additional training for practitioners. Some components of the intervention were not experienced as intended; this appeared to reflect difficulties with operationalising the intervention. Analysis of data relating to the intended outcomes of the intervention indicated that the mechanisms proposed in the programme theory had operated as expected. CONCLUSIONS: Additional implementation support is likely to be required for the PARTNERS model to be delivered; the effectiveness of such support may be affected by practitioner and service user readiness to change. There is also a need to test the programme theory more fully. These issues will be addressed in the process evaluation of our full trial. TRIAL REGISTRATION: ISRCTN95702682 , 26 October 2017.

An investigation of social determinants of health and outcomes in pediatric nonaccidental trauma.

OBJECTIVES: Nonaccidental trauma (NAT) is a leading cause of pediatric mortality and disability. We examined our institution's experience with NAT to determine if socioeconomic status is correlated with patient outcomes. METHODS: NAT cases were reviewed retrospectively. Socioeconomic determinants included insurance status and race; outcomes included mortality, discharge disability and disposition. Correlations were identified using t test, Fisher's exact test, and logistic regression. RESULTS: The cohort comprised of 337 patients, with an overall uninsured rate of 5.6%. This rate was achieved by insuring 64.7% of the cohort after admission. Non-survivors were more likely to have no insurance coverage (14.8% versus 4.8%, p = 0.041). Regression revealed that uninsured had 8 times (95% CI 1.7-38.7, p = 0.008) higher in-hospital mortality than those with insurance when controlling for injury severity. Additionally, injury severity score ≥ 15, transfer from outside hospital, need for ICU or operative treatment were predictive of mortality. Adjusted risk factors for severe disability at discharge did not include insurance status or race, while ISS ≥ 15 and ICU stay were predictive. CONCLUSIONS: There are significant associations of insurance status with pediatric NAT outcomes, highlighting that determinants other than disease severity may influence mortality and morbidity. High-risk patients should be identified to develop strategies to improve outcomes.

Correlation of payor status and pediatric transfer for acute appendicitis.

BACKGROUND: Tertiary referral centers provide specialty and critical care for patients presenting to hospitals that lack these resources. There is a notion among tertiary centers that outside hospitals are more likely to transfer uninsured or underinsured patients. We examined funding status of patients transferred to our tertiary pediatric hospital for surgical management of appendicitis, hypothesizing that transferred patients were more likely to have unfavorable coverage. MATERIALS AND METHODS: The electronic medical record was queried for all cases of laparoscopic appendectomy at our hospital between 2011 and 2015. Insurance was grouped into three categories: commercial, Medicaid/Children's Health Insurance Plan, or none. Transferred patients were compared to patients who presented directly. RESULTS: A total of 5758 patients underwent laparoscopic appendectomy during the study period, of which 1683 (29.2%) were transfer patients. Transfer patients were more likely to be older, with a median age of 10.5 y versus 9.8 y in nontransferred patients (P ≤ 0.0001), and were more likely to be identified as non-Hispanic (50.0% versus 36.5%; P ≤ 0.0001). Insurance coverage was similar between groups. However, subgroup analysis of the hospitals that most frequently used our transfer services revealed a trend to transfer a higher proportion of Medicaid/Children's Health Insurance Plan patients. CONCLUSIONS: Overall, pediatric patients transferred for laparoscopic appendectomy had similar insurance coverage to patients admitted directly, but subgroup analysis shows that not all centers follow this trend. Transfer patients were more frequently older and non-Hispanic. This builds upon the existing literature regarding the correlation of funding and transfer practices and highlights the need for additional research in this area.

Interleukin 4 and interleukin 13 downregulate the lipopolysaccharide-mediated inflammatory response by human gestation-associated tissues.

Inflammation is a key feature of preterm and term labor. Proinflammatory mediators are produced by gestation-associated tissues in response to pathogen-associated molecular patterns and damage-associated molecular patterns. Interleukin (IL)4, IL10, and IL13 are anti-inflammatory cytokines with potential as anti-inflammatory therapies to prevent preterm birth. The objective of this study was to determine if IL4 and IL13 exert anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated production of proinflammatory cytokines produced by human term gestation-associated tissues (placenta, choriodecidua, and amnion). Both IL4 and IL13 reduced LPS-stimulated IL1B and macrophage inflammatory protein1A; this effect diminished with delay to exposure to either cytokine. There was no effect on LPS-stimulated prostaglandin production. Interleukin 4 receptor alpha (IL4RA) was expressed throughout the placenta, choriodecidua, and amnion, and the inhibitory effects of IL4 and IL13 were IL4RA dependent. Combined IL4 and IL13 did not enhance the anti-inflammatory potential of either cytokine; however, a combination of IL4 and IL10 had a greater anti-inflammatory effect than either cytokine alone. These findings demonstrate that human term gestation-associated tissues are responsive to the anti-inflammatory cytokines IL4 and IL13, which could downregulate LPS-induced cytokine production in these tissues. Anti-inflammatory cytokines might offer an adjunct to existing therapeutics to prevent adverse obstetric outcome.

Production and regulation of interleukin-1 family cytokines at the materno-fetal interface.

IL-1 family members regulate innate immune responses, are produced by gestation-associated tissues, and have a role in healthy and adverse pregnancy outcomes. To better understand their role at the materno-fetal interface we used a human tissue explant model to map lipopolysaccharide (LPS)-stimulated production of IL-1α, IL-1ß, IL-18, IL-33, IL-1Ra, IL-18BPa, ST2 and IL-1RAcP by placenta, choriodecidua and amnion. Caspase-dependent processing of IL-1α, IL-1ß, IL-18, and IL-33 and the ability of IL-1α, IL-1ß, IL-18, and IL-33 to regulate the production of IL-1RA, IL-18BPa, ST2 and IL-1RAcP was also determined. LPS acted as a potent inducer of IL-1 family member expression especially in the placenta and choriodecidua with the response by the amnion restricted to IL-1ß. Caspases-1, 4 and 8 contributed to LPS-stimulated production of IL-1ß and IL-18, whereas calpain was required for IL-1α production. Exogenous administration of IL-1α, IL-1ß, IL-18, and IL-33 lead to differential expression of IL-1Ra, IL-18BPa, ST2 and IL-1RAcP across all tissues examined. Most notable were the counter-regulatory effect of LPS on IL-1ß and IL-1Ra in the amnion and the broad responsiveness of the amnion to IL-1 family cytokines for increased production of immunomodulatory peptides and soluble receptors. The placenta and membranes vary not only in their output of various IL-1 family members but also in their counter-regulatory mechanisms through endogenous inhibitory peptides, processing enzymes and soluble decoy receptors. This interactive network of inflammatory mediators likely contributes to innate defence mechanisms at the materno-fetal interface to limit, in particular, the detrimental effects of microbial invasion.

End-user involvement in a systematic review of quantitative and qualitative research of non-pharmacological interventions for attention deficit hyperactivity disorder delivered in school settings: reflections on the impacts and challenges.

BACKGROUND: The benefits of end-user involvement in health-care research are widely recognized by research agencies. There are few published evaluations of end-user involvement in systematic reviews. OBJECTIVES: (i) Describe end-user involvement in a complex mixed-methods systematic review of ADHD in schools, (ii) reflect on the impact of end-user involvement, (iii) highlight challenges and benefits experienced and (iv) provide suggestions to inform future involvement. METHODS: End-users were involved in all stages of the project, both as authors and as members of an advisory group. In addition, several events were held with groups of relevant end-users during the project. RESULTS: End-user input (i) guided the direction of the research, (ii) contributed to a typology of interventions and outcomes, (iii) contributed to the direction of data analysis and (iv) contributed to the robustness of the syntheses by demonstrating the alignment of interim findings with lived experiences. Challenges included (i) managing expectations, (ii) managing the intensity of emotion, (iii) ensuring that involvement was fruitful for all not just the researcher, (iv) our capacity to communicate and manage the process and (v) engendering a sense of involvement amongst end-users. CONCLUSIONS: End-user involvement was an important aspect of this project. To minimize challenges in future projects, a recognition by the project management team and the funding provider that end-user involvement even in evidence synthesis projects is resource intensive is essential to allow appropriate allocation of time and resources for meaningful engagement.

Teaching examples for the design of experiments: geographical sensitivity and the self-fulfilling prophecy.

Many scientists believe that small experiments, guided by scientific intuition, are simpler and more efficient than design of experiments. This belief is strong and persists even in the face of data demonstrating that it is clearly wrong. In this paper, we present two powerful teaching examples illustrating the dangers of small experiments guided by scientific intuition. We describe two, simple, two-dimensional spaces. These two spaces give rise to, and at the same time appear to generate supporting data for, scientific intuitions that are deeply flawed or wholly incorrect. We find these spaces useful in unfreezing scientific thinking and challenging the misplaced confidence in scientific intuition.

Exploring how nurses and managers perceive shared governance.

BACKGROUND: Nurse managers have a pivotal role in the success of unit-based councils, which include direct care nurses. These councils establish shared governance to provide innovative, quality-based, and cost-effective nursing care. PURPOSE: This study explored differences between direct care nurses' and nurse managers' perceptions of factors affecting direct care nurses' participation in unit-based and general shared governance activities and nurse engagement. METHODS: In a survey research study, 425 direct care RNs and nurse managers were asked to complete a 26-item research survey addressing 16 shared governance factors; 144 participated (response rate = 33.8%). RESULTS: Most nurse participants provided direct care (N = 129, 89.6%; nurse managers = 15, 10.4%), were older than 35 (75.6%), had more than 5 years of experience (76.4%), and worked more than 35 hours per week (72.9%). Direct care nurses' and managers' perceptions showed a few significant differences. Factors ranked as very important by direct care nurses and managers included direct care nurses perceiving support from unit manager to participate in shared governance activities (84.0%); unit nurses working as a team (79.0%); direct care nurses participating in shared governance activities won't disrupt patient care (76.9%); and direct care nurses will be paid for participating beyond scheduled shifts (71.3%). Overall, 79.2% had some level of engagement in shared governance activities. Managers reported more engagement than direct care nurses. CONCLUSIONS: Nurse managers and unit-based councils should evaluate nurses' perceptions of manager support, teamwork, lack of disruption to patient care, and payment for participation in shared governance-related activities. These research findings can be used to evaluate hospital practices for direct care nurse participation in unit-based shared governance activities.

Identifying the causes of contact dermatitis.

Contact dermatitis results from skin contact with an exogenous substance. It can be caused by direct contact, airborne particles, vapours or light. Individuals of any age can be affected. The two most common variants are irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). ICD is more common and has a worse prognosis. Other less common forms of contact dermatitis include photocontact allergy and, in food handlers, protein contact dermatitis. ICD is a form of eczema and is induced by direct inflammatory pathways without prior sensitisation. Classical ACD is mediated by type 4 cell-mediated immunity. Sensitisation occurs within 5 to 16 days of skin contact with a potential allergen but at this first exposure there is no inflammation. Frequent exposure and high concentrations of potential allergens increase the risk of sensitisation. If eczema is recurrent/persistent, or occurs in an individual with no previous history of eczema, contact dermatitis should be considered. Dorsal aspects of the hands are most often affected by ICD, usually with involvement of the finger webs. Cumulative effects of water, soaps and detergents are the most common cause of ICD which affects the hands more often than any other site. Nickel, fragrances, rubber accelerators and biocides are the most common sensitisers in ACD. Patients with leg ulcers and stasis eczema are at especially high risk of developing allergies to ingredients of their topical treatments, dressings and bandages. If ACD is suspected the patient should be referred to secondary care for patch testing. Age should not be a deterrent to patch testing. Accurate diagnosis, avoidance of identified allergens and protection from irritants are the key to successful treatment.

Effect of Medial Patellofemoral Complex Reconstruction Technique on Patellofemoral Contact Pressure, Contact Area, and Kinematics.

BACKGROUND: Medial patellofemoral ligament (MPFL) reconstruction is considered by many to be the gold standard to treat lateral patellar instability; however, some investigators have reported good clinical results after isolated medial quadriceps tendon-femoral ligament (MQTFL) reconstruction or a combined MPFL/MQTFL reconstruction. A handful of studies have preliminarily investigated the biomechanical consequences of these various medial patellar stabilizing procedures. Despite this, no existing study has included multiple medial patellofemoral complex (MPFC) reconstructions and assessment of lateral patellar translation at distinct flexion angles. HYPOTHESIS: Combined MPFL/MQTFL reconstruction would restore patellofemoral contact areas, forces, and kinematics closest to the native state compared with isolated reconstruction of the MPFL or MQTFL alone. STUDY DESIGN: Controlled laboratory study. METHODS: Ten adult cadaveric knee specimens were prepared and analyzed under 5 different conditions: (1) intact state, (2) transected MPFC, (3) isolated MPFL reconstruction, (4) isolated MQTFL reconstruction, and (5) combined MPFL/MQTFL reconstruction. Patellar tilt, lateral patellar translation, patellofemoral contact forces, and patellofemoral contact areas were measured in each condition from 0° to 80° through simulated knee flexion using a custom servohydraulic load frame with pressure sensor technology and a motion capture system for kinematic data acquisition. RESULTS: The isolated MPFL, isolated MQTFL, and combined MPFL/MQTFL reconstruction conditions produced significantly less lateral patellar tilt compared with the transected MPFC state (P < .05). No statistically significant differences were found when each reconstruction technique was compared with the intact state in patellar tilt, lateral patellar translation, contact forces, and contact areas. CONCLUSION: All 3 reconstruction techniques (isolated MPFL reconstruction, isolated MQTFL reconstruction, and combined MPFL/MQTFL reconstruction) restored native knee kinematics, contact forces, and contact areas without overconstraint. CLINICAL RELEVANCE: Isolated MPFL reconstruction, isolated MQTFL reconstruction, and combined MPFL/MQTFL reconstruction all restore patellofemoral stability comparable with the intact MPFC state without the overconstraint that could be concerning for increasing risk of patellofemoral arthritis.

No difference in stability among various knee flexion angles during fixation of anterolateral ligament reconstruction or lateral extra-articular tenodesis: A systematic review and meta-analysis of biomechanical studies.

Purpose: The purpose of this study was to investigate the effect of anterolateral ligament reconstruction (ALLR) or lateral extra-articular tenodesis (LET) fixation at low versus high flexion angles during anterior cruciate ligament reconstruction (ACLR) on rotation or translational knee stability. Methods: The inclusion criteria for this study were (1) cadaveric study, (2) cadaveric specimens underwent ACLR, (3) cadaveric specimen underwent ALLR or LET and (4) specimen preparation technique described the knee flexion angle at the time of ALLR or LET tensioning and fixation. A priori, 'low flexion' was defined as 0-30° and 'high flexion' was defined as 60-90° at graft fixation. Main outcomes of interest included internal rotation and anterior translation. Results: Data from 92 cadaveric knees (from 9 studies) were extracted and included in the meta-analysis. The mean pooled value for internal rotation was 10.1° (95% confidence interval [CI], 5.7-14.5°) for the low flexion group and 11.5° (95% CI, 7.4-15.7°) for the high flexion group (n.s.). The mean pooled value for anterior translation was 4.3 mm (95% CI, 0.5-8.1 mm) for the low flexion group and 3.0 mm (95% CI, 1.1-5.0 mm) for the high flexion group (n.s.). Conclusion: This meta-analysis of existing biomechanical research found that the rotational and translational stability of the knee were not significantly different between scenarios in which ALLR or LET fixation was performed at low knee flexion angles (0-30°) versus high knee flexion angles (60-90°). Level of Evidence: Level IV.