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Head and neck microvascular reconstruction is a complex but powerful tool following immediate cancer ablation or delayed sequalae after cancer treatment. Virtual surgical planning (VSP), using computer-aided design or computer-aided manufacturing has emerged as a potentially beneficial adjunct to head and neck reconstruction. The aim of this study was to assess the outcomes of VSP technology using the KLS Martin custom-made cutting guides and low-profile plates in head and neck microvascular reconstruction in our centre. A retrospective study was conducted at the regional head and neck centre in the UK from March 2017 until June 2023. A total of 127 patients were included. Among them, 77.8% of the patients underwent immediate reconstruction following cancer ablative procedure, with 22.2% being treated for osteoradionecrosis. Median flap ischaemia time was 130 min (45–360 min). Median number of osteotomies was 1 (0−3). Median operative time was 622 min (302–962 min). Procedural complications occurred in 16.2% of the patients. Total flap failure rate was 6.35%. This study found that patients who were operated on with palliative intent had significantly worse flap survival rates (p < 0.033). The length of hospital stay was significantly impacted by longer operative time (p < 0.002) and overall length of intensive therapy unit stay was significantly increased in diabetic and palliative patients. Three-dimensional planning software has become a standard of care within our centre, leading to shorter operative time, reliable and accurate reconstruction and a short learning curve for skill acquisition. Extensive surgery in palliative patients requires a robust consenting process in the context of a multi-disciplinary team discussion. [ABSTRACT FROM AUTHOR]

Open lower limb fractures are severe injuries with long-lasting consequences. Limited research has been conducted on the impact of these injuries on quality of life (QoL), internationally. The Quality of Life after Open Extremity Trauma (QUINTET) study was designed as an international, multicentric, observational, cohort study of patients presented with open lower limb fractures. Demographic and clinical information was collected, along with repeated validated QoL measures. Primary outcomes were SF-12 and EQ-5D-3L, and secondary outcomes were soft tissue infection, deep infection, non-union and amputation. A total of 92 patients were enrolled in 8 centres, based in the UK, Spain, Chile and Sudan. The mean age at presentation was 54 years, 47 years for males and 64 years for females. Males presented a higher proportion of road traffic accidents as the underlying mechanism, whereas for females, this was the case of low-energy falls. Participant retention was 71.7% and 73.9% for the 3- and 12-month assessments, respectively. There was a substantial reduction in QoL after open fracture, which only partially recovered at 12 months. Participants recruited in the UK presented lower QoL scores compared with patients treated in Spain and Chile. For this study, international patient recruitment proved challenging, leading to most patients being recruited in the UK. Despite this limitation, we found a statistically significant detriment in self-reported QoL, which did not recover after a year. This study highlights differences in quality-of-life outcomes from a gender and international perspective. [ABSTRACT FROM AUTHOR]

Growing awareness of social inequities and injustices in education highlights the urgent need to address harmful mechanisms, policies, and norms within health education curricula and systems. This study examines inclusivity and exclusivity content in four fundamental nursing textbooks and contributes to the broader discourse on fostering equitable health education. A Directed Qualitative Content Analysis on 32 chapters from four fundamental nursing textbooks was systematically conducted. Seven codes within inclusivity and exclusivity themes were deductively developed from the literature. Inclusivity codes included equity language and contextualized race-based prevalence. Exclusivity codes included normalizing Whiteness in assessment, stigmatizing and negative descriptors, race-based prevalence without context, cisgenderism, and othering. Two trained analysts independently reviewed the chapters, assigning texts to these codes. Discrepancies were resolved by team consensus. A total of 118 inclusivity instances: equity language (n = 109) and race-based prevalence with context (n = 9). Exclusivity codes were more prevalent (n = 642), including normalizing Whiteness (n = 398), stigmatizing descriptors (n = 106), cisgenderism (n = 59), and othering (n = 32). The study highlights inclusive language in fundamental nursing textbooks but reveals significant exclusive language perpetuating negative generalizations, including marginalized identities and race prevalence without context. This content undermines person-centered care and hinders understanding the complex interplay between intersectionality, social justice, and social determinants of health. • Textbooks should incorporate information that highlights socio-historical-political context as critical drivers of health risks and inequities in healthcare. • Exclusivity persists in nursing textbooks, often normalizing Whiteness and excluding diverse realities. • Revisions in nursing educational materials are essential to address health equity and improve culturally informed care. • Significant disparities in how nursing textbooks address race, gender, and social determinants of health may hinder nursing students' ability to deliver equitable and inclusive care. [ABSTRACT FROM AUTHOR]

Lymphedema microsurgery is an emerging treatment modality, with dissimilar long-term outcomes. One of the main technical challenges in lymphatic microsurgery is the identification and availability of suitable donor vessels for anastomosis. Tissue engineering using biomaterials has demonstrated promise in addressing vessel quality issues in other fields, but its application in microsurgery is still limited. Decellularized cellulose tubes were developed and bioengineered by decellularizing stems of Taraxacum-Ruderalia. The microscopic structure, mechanical properties, and residual DNA content of the cellulose tubes were evaluated. Human and murine skin fibroblasts and dermal lymphatic endothelial cells were isolated and cultured for recellularization studies. Biocompatibility, proliferative capacity, and ex-vivo endothelialization of the cellulose tubes were assessed as potential interposition grafts. Finally, the engineered cellulose tubes were assessed as interposing xenografts for lymphovenous anastomoses (LVA) in an ex-vivo swine limb model. The decellularized cellulose tubes exhibited a suitable microscopic structure, mechanical properties, and low residual DNA content. The tubes showed adequate biocompatibility, supported cell proliferation, and facilitated spontaneous ex-vivo endothelialization of lymphatic endothelial cells. In the swine limb model, LVA using the engineered cellulose tubes was successfully performed. This translational study presents the use of decellularized cellulose tubes as an adjunct for micro and supermicrosurgical reconstruction. The developed tubes demonstrated favorable structural, mechanical, and biocompatible properties, making them a potential candidate for improving long-term outcomes in lymphedema surgical treatment. The next translational step would be trialing the obtained tubes in a microsurgical in-vivo model. [ABSTRACT FROM AUTHOR]

Patients undergoing autologous breast reconstruction usually require further operations as part of their reconstructive journey. This involves contralateral breast symmetrization and nipple-areola complex (NAC) reconstruction. Restrained access to elective operating space led us to implement a one-stop breast reconstruction pathway. Patients undergoing contemporaneous contralateral breast symmetrization and immediate NAC reconstruction with free nipple grafts between July 2020 and June 2021 were identified. A retrospective review of our prospectively maintained database was conducted, to retrieve surgical notes, postoperative complications, and length of inpatient stay. A cost analysis was performed considering savings from contralateral symmetrization. A total of 50 eligible cases were identified, which had unilateral one-stop breast reconstructions. Complication rates and length of stay were not affected by this approach, with only one free flap being lost for this cohort. This approach resulted in £181,000 being saved for our service over a calendar year. A one-stop breast reconstruction pathway has proven to be safe and effective in our unit. During these uncertain times, it has streamlined the management of eligible patients, while releasing capacity for other elective operations. Patients avoid having to wait for secondary procedures, finishing their reconstructive pathway earlier. We plan to continue providing this service which has shown to be beneficial clinically and financially. [ABSTRACT FROM AUTHOR]

Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022. Using different media, we recruited Ukrainian refugees at 13 sites between 9–12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration. Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children. Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B. We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cold gas plasma-generated ROS have anticancer potential. • A 154-drug library screening was performed in 3D tumor spheroids using quantitative high-content imaging analysis. • Candidates combining well with ROS-mediated anticancer effects were analyzed. • A compound was identified with low toxicity that amplified ROS-derived tumor toxicity in vitro , in ovo, and in vivo. Skin cancer is often fatal, which motivates new therapy avenues. Recent advances in cancer treatment are indicative of the importance of combination treatments in oncology. Previous studies have identified small molecule-based therapies and redox-based technologies, including photodynamic therapy or medical gas plasma, as promising candidates to target skin cancer. We aimed to identify effective combinations of experimental small molecules with cold gas plasma for therapy in dermato-oncology. Promising drug candidates were identified after screening an in-house 155-compound library using 3D skin cancer spheroids and high content imaging. Combination effects of selected drugs and cold gas plasma were investigated with respect to oxidative stress, invasion, and viability. Drugs that had combined well with cold gas plasma were further investigated in vascularized tumor organoids in ovo and a xenograft mouse melanoma model in vivo. The two chromone derivatives Sm837 and IS112 enhanced cold gas plasma-induced oxidative stress, including histone 2A.X phosphorylation, and further reduced proliferation and skin cancer cell viability. Combination treatments of tumor organoids grown in ovo confirmed the principal anti-cancer effect of the selected drugs. While one of the two compounds exerted severe toxicity in vivo , the other (Sm837) resulted in a significant synergistic anti-tumor toxicity at good tolerability. Principal component analysis of protein phosphorylation profiles confirmed profound combination treatment effects in contrast to the monotherapies. We identified a novel compound that, combined with topical cold gas plasma-induced oxidative stress, represents a novel and promising treatment approach to target skin cancer. [ABSTRACT FROM AUTHOR]

Angiosarcomas in the head and neck region are aggressive tumours associated with high local recurrence and metastatic rates. We present our 17-year experience at the North of England Bone and Soft Tissue Tumour Service. A retrospective review of our prospectively maintained database was undertaken, looking for patients diagnosed with angiosarcomas affecting the head and neck. Data were gathered using a pre-defined proforma to include demographics, histological characteristics, treatment modalities, adjuvant therapies, local recurrence, distant spread, and disease-specific survival. A total of 23 patients (17 males, 6 females) were identified, with a mean age of 76 years at presentation. Fourteen presented with scalp lesions, whereas the remainder arose on the face. Eighteen patients underwent resection with curative intent, whereas three received palliative radiotherapy and two received comfort-based care only. Of the patients undergoing surgery, 12 had local flap reconstruction and 6 underwent free tissue transfer. Clear resection margins were obtained in nine cases (50%). Fourteen patients (78%) presented with local recurrence after surgery, and 11 (61%) developed distant metastases. The median disease-specific survival time for patients treated with curative intent was 38 months. Eight patients had mapping biopsies ahead of their resection; however, complete resection was achieved in only two cases. Angiosarcomas of the head and neck are associated with a poor prognosis, with most patients rapidly developing local recurrence, resulting in adverse clinical outcomes. Mapping biopsies do not demonstrate a clear advantage for achieving complete surgical resection. A radical surgical approach is warranted, given the aggressiveness of the pathology. However, there remains no consensus on optimal surgical management; we recommend further synthesising studies to determine the most appropriate treatment pathway. [ABSTRACT FROM AUTHOR]

To examine whether pain sensitization is associated with hand and lower extremity function in people with hand osteoarthritis (OA) in the Nor-Hand study. Pain sensitization was assessed by pressure pain thresholds (PPTs) and temporal summation (TS). Hand function was assessed by Australian/Canadian Osteoarthritis Hand Index (AUSCAN) (range: 0–36), grip strength and Moberg pick-up test, and lower extremity function was assessed by Western Ontario and McMaster Universities Osteoarthritis Index (range: 0–68), 30-s chair stand test, and 40-m walk test. We examined whether sex-standardized PPT and TS values were cross-sectionally associated with measures of physical function using linear regression analyses. Beta coefficients were presented per sex-specific standard deviation of PPT and TS. The mediating effect of pain was examined by causal-inference based mediation analysis. In 206 participants, higher PPTs at/near the hand, indicative of less peripheral and/or central pain sensitization, were associated with greater grip strength and better self-reported hand function (beta for PPT at finger joint on AUSCAN function: −1.41, 95% CI −2.40, −0.42). Higher PPTs at/near the hand, near the knee and at trapezius were associated with lower extremity function, although not statistically significant for all outcomes. Self-reported pain severity mediated the effect of PPT on self-reported function. TS was not associated with hand or lower extremity function. Peripheral sensitization, and possibly central sensitization, was associated with impaired function. Effects of PPTs on self-reported function were mediated by self-reported pain, whereas there might be a direct effect of sensitization or effects through other mediators on performance-based function. [ABSTRACT FROM AUTHOR]

For aggressive limb sarcomas beyond reconstructive reach, an amputation may be the only alternative to achieve a complete tumour resection. However, very proximal amputations result in greater loss of function and quality-of-life impact. The spare parts principle advocates utilising tissues distal to the amputation site, for reconstructing complex defects and preserving the function. We aim to present our 10-year experience utilising this principle in complex sarcoma surgery. A retrospective review of our prospective sarcoma database was conducted for sarcoma patients treated with an amputation between 2012 and 2022. Cases in which distal segments were used for the reconstruction were identified. Demographic data, tumour characteristics, and surgical and non-surgical treatment, along with oncological outcomes and complications, were recorded and analysed. Fourteen patients were eligible for inclusion. The median age was 54 years at presentation (8–80 years) with 43% being females. Nine had a primary sarcoma resection, two were treated for recurrent tumours, two presented intractable osteomyelitis following sarcoma treatment and one had an amputation as a palliative procedure. The latter was the only oncological case in which tumour clearance was not achieved. Three patients developed metastasis and subsequently died during follow-up. Careful balancing of oncological goals and preservation of function is required for proximal limb-threatening sarcomas. When an amputation is required, tissues distal to the cancer site provide a safe reconstructive alternative, optimising patient recovery and preserving function. Our experience is limited by the small number of cases presenting with these rare and aggressive tumours. [ABSTRACT FROM AUTHOR]

[Display omitted] • Gas plasma is a novel ROS-generating tool that can be used in oncology. • Bladder cancer cells in 2D, 3D, semi- in vivo (in ovo), and in patient-derived samples were employed. • Tumor cells in all models were inactivated following gas plasma treatment. • The reactive oxygen species production was assessed in detail. • Several mechanistic targets identified in cancer patient tissues, such as FGFR3, using whole transcriptome analysis. Medical gas plasma therapy has been successfully applied to several types of cancer in preclinical models. First palliative tumor patients suffering from advanced head and neck cancer benefited from this novel therapeutic modality. The gas plasma-induced biological effects of reactive oxygen and nitrogen species (ROS/RNS) generated in the plasma gas phase result in oxidation-induced lethal damage to tumor cells. This study aimed to verify these anti-tumor effects of gas plasma exposure on urinary bladder cancer. 2D cell culture models, 3D tumor spheroids, 3D vascularized tumors grown on the chicken chorion-allantois-membrane (CAM) in ovo , and patient-derived primary cancer tissue gas plasma-treated ex vivo were used. Gas plasma treatment led to oxidation, growth retardation, motility inhibition, and cell death in 2D and 3D tumor models. A marked decline in tumor growth was also observed in the tumors grown in ovo. In addition, results of gas plasma treatment on primary urothelial carcinoma tissues ex vivo highlighted the selective tumor-toxic effects as non-malignant tissue exposed to gas plasma was less affected. Whole-transcriptome gene expression analysis revealed downregulation of tumor-promoting fibroblast growth factor receptor 3 (FGFR3) accompanied by upregulation of apoptosis-inducing factor 2 (AIFm2), which plays a central role in caspase-independent cell death signaling. Gas plasma treatment induced cytotoxicity in patient-derived cancer tissue and slowed tumor growth in an organoid model of urinary bladder carcinoma, along with less severe effects in non-malignant tissues. Studies on the potential clinical benefits of this local and safe ROS therapy are awaited. [ABSTRACT FROM AUTHOR]

Collective approaches for agri-environmental measures are known for aiming at spatial coordination of measures to enhance ecological effectiveness. In the Netherlands, governance networks for agri-environmental measures are centered around agricultural collectives that function as intermediaries between individual farmers and governmental as well as non-governmental actors. Against the background that some agricultural collectives are bottom-up and other top-down initiated, we analyzed in how far they can build up social capital through formal and informal relations. We used the Net-Map method to collect qualitative and quantitative data for a Social Network Analysis to uncover the network characteristics that contribute to a certain level of social capital. The results revealed that the umbrella organization links the collectives to the national governmental level and to other collectives. This is especially important for top-down initiated collectives. The facilitation of internal meetings within the collectives is important for social learning. Furthermore, a formalization of the exchange between collectives and stakeholders of nature conservation could strengthen cooperation where traditionally conflicts dominate. By analyzing interaction in detail, the social reasoning to promote collective agri-environmental measures was highlighted. They enable collaboration of different stakeholders at multiple levels to the end that knowledge and resources are bundled. • There is a social reasoning to promote collective agri-environmental measures, next to spatial coordination. • Collective agri-environmental measures enable collaboration of different stakeholders. • Agricultural collectives build up social capital through formal and informal relations at multiple levels. [ABSTRACT FROM AUTHOR]

• The study highlights the challenges in assessing disease activity among rheumatoid arthritis patients with anxiety or depression, as well as the higher burden of patient-reported outcome measures, unemployment, worse self-evaluated economy and sleep difficulties among these patients. • As assessed by a comprehensive ultrasound assessment, disease activity was similar between patients with and without anxiety or depression, contrasting the higher disease activity found in those experiencing anxiety or depression when using a comprehensive clinical assessment. • The study advocates for the consideration of objective methods, such as ultrasound assessments, in evaluating disease activity among rheumatoid arthritis patients dealing with anxiety or depression. To compare disease activity as assessed by ultrasonography (US) between rheumatoid arthritis (RA) patients with and without anxiety or depression, and to compare clinical disease activity and sociodemographic measures between these patient groups. Anxious or depressed patients were identified by EuroQoL-5D-3L question "I am not/moderately/extremely anxious or depressed." US assessments of 36 joints and 4 tendons were performed and power Doppler (PD) and grey scale (GS) sum scores calculated (both range 0–120). Comparisons between anxious/depressed and not anxious/depressed patients were performed in unadjusted analyses, adjusted logistic regression, and sensitivity analyses. A total of 201 RA patients starting biological disease-modifying antirheumatic drugs were included (82 % women, mean age 52 years, disease duration 10 years). Hundred-and-nine patients (54.2 %) were moderately or extremely anxious/depressed. Median (IQR) PD (13 (4, 21) vs. 10 (3, 20), p = 0.53) and GS (28 (18, 42) vs. 25 (14, 41), p = 0.51) sum scores were similar between anxious/depressed and not anxious/depressed patients, respectively, whereas composite scores of disease activity were significantly worse in the anxious/depressed patients (p < 0.001), as were also patient-reported outcomes, ESR, CRP and plasma calprotectin (all p ≤ 0.02). Sensitivity analyses confirmed these findings, except for CRP. Self-reported economy and sleep difficulties were also worse in the anxious/depressed patients and a higher proportion were not working (all p < 0.001). This study highlights the negative impact of anxiety and depression on RA patients in standard care, and underscores the challenges in disease activity assessment. US examination may be a valuable objective tool in the evaluation of these patients. [Display omitted] [ABSTRACT FROM AUTHOR]

There is evidence that gender-affirming hormone treatment (GAHT) for transgender individuals modulates their risk for specific malignancies including breast and prostate cancer, and meningiomas. However, there is insufficient data to make precise risk estimates accounting for age and inherited cancer risk. As such, screening recommendations remain broad. Even less evidence exists for best practice in the management of active or historical cancers in the transgender population. Guidance is therefore mainly extrapolated from cisgender populations but with considerations of the significant benefits of GAHT in the face of any hormonal risk. Clinical experience, the multidisciplinary team and shared decision making with the patient are vital in providing person-centred care, while further research is acquired. [ABSTRACT FROM AUTHOR]

To investigate the frequency and consequences of wheelchair repairs, looking at the relationship to usage, components, out-of-pocket costs, number of days affecting the user, and factors associated with the need for repairs or consequences. Survey, cross-sectional. Nine spinal cord injury (SCI) Model Systems centers. Wheelchair users with SCI (N=533). Not applicable. Cost and incidence of wheelchair repairs and consequences and wheelchair usage within the past 6 months. A total of 310 participants (56%) reported repairs, 127 (42%) of whom experienced at least 1 adverse consequence lasting a median of 5 days (interquartile range [IQR], 2-17.3 days). Repair rates were highest for the seating system, electronics, and tires. Participants were most often stranded at home or forced to use a backup chair. Median out-of-pocket costs were $150 (IQR, $50-$620). Active users, based on type of mobility and terrain, experienced more repairs and consequences than less active users. Repairs were more common among those who were Black (odds ratio [OR], 2.42) or power wheelchair (PWC) users (OR, 1.84), whereas consequences were more common among those who were Black (OR, 2.27), PWC (OR, 2.08) or power assist users (OR, 2.76), and those who had public insurance (OR, 1.70). Wheelchair repairs continue to affect more than 50% of wheelchair users with significant financial and personal cost. High repair rates limited participation inside and outside of the home. Consequences lasted longer than 2 weeks for many and may be minimized by a working backup chair. Disparities exist based on participant and wheelchair factors; repairs and adverse consequences appear to hit those most vulnerable with the least financial resources. Costs may be a barrier to repair completion for some individuals. This ongoing problem of high repair rates and their associated effects requires action such as higher standards, access to quicker service, and better training of users on wheelchair maintenance and repair. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of childcare facilities in the transmission of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in a longitudinal study to gain further knowledge of SARS-CoV-2 prevalence, transmission, and spread among preschool children, their parents, and their caregivers.Study Design: Children aged 1-6 years, their parents, and their caregivers in 14 childcare facilities in Dresden, Saxony/Germany were invited to participate in the KiTaCoviDD19-study between July 2020 and January 2021. Seroprevalence of SARS-CoV-2 antibodies was assessed up to 4 times during the study period in all participating adults, and demographic characteristics, as well as epidemiologic information on personal SARS-CoV-2 history were obtained. Samples for stool virus shedding of SARS-CoV-2 were analyzed by polymerase chain reaction every 2-4 weeks in all participating children.Results: In total, 318 children, 299 parents and 233 childcare workers were enrolled. By January 2021, 11% of the participating adults were found to be seropositive, whereas the percentage of children shedding SARS-CoV-2 was 6.8%. Overall, we detected 17 children with SARS-CoV-2 virus shedding in 8 different childcare facilities. In 4 facilities, there were a maximum of 3 connected cases in children. Approximately 50% of SARS-CoV-2 infections in the children could not be connected to a secondary case in our study population.Conclusions: This study does not provide evidence of relevant asymptomatic ("silent") spread of SARS-CoV-2 in childcare facilities in both low- and high-prevalence settings. Our findings add to the evidence that childcare and educational settings do not have a crucial role in driving the SARS-CoV-2 pandemic. [ABSTRACT FROM AUTHOR]

Myxofibrosarcomas are associated with a locally infiltrative growth pattern, making a clear-margin resection margin challenging. This leads to high local recurrence rates. While immediate wound closure and adjuvant radiotherapy has been proposed to mitigate incomplete excisions, we present our experience treating myxofibrosarcomas with staged excisions until clear margins are obtained, prior to reconstruction. All patients with myxofibrosarcomas treated with a curative intent at our centre between 2009 and 2019 were identified. Patient demographics, tumour characteristics, number of resections, method of reconstruction, adjuvant therapy, complications, local recurrence rates, length of hospital stay and overall survival were assessed. 97 consecutive eligible patients were identified. Forty-six (47%) had positive margins reported following a first resection. The median number of resections required to obtain clear margins was two and the median time from first excision to definitive wound closure was 15 days. Local recurrence rate for the whole cohort was 14%. Patients who had staged resection until clear margins were obtained had a significantly lower rate of local recurrence compared to those who had positive margins at time of reconstruction (p-value = 0.001). The estimated 5-year disease-specific survival for the whole cohort was 93%. Obtaining clear margins in myxofibrosarcoma via staged resections was associated with lower local recurrence rates for patients who had an initial resection with positive margins. The outcomes of performing staged resections are equivalent to patients for whom a clear margin were obtained in the first instance. [ABSTRACT FROM AUTHOR]

Limb-threatening sarcomas invading major vessels present an oncological and reconstructive challenge. Curative resection involves either performing an amputation or an immediate reconstruction of the invaded vessels. We present our 15-year experience of these cases at the North of England Bone and Soft Tissue Tumour Service. A Strengthening the Reporting of Observational studies in Epidemiology (STROBE) compliant retrospective review of our prospective database was performed including patients who required major vessel reconstruction following sarcoma excision from 2003 until 2018. Patient demographic data along with tumour and histological subtypes, treatment modality, complications and outcomes were inquired. Autologous and prosthetic vessel reconstruction approaches were compared. Nineteen patients were identified with the most common tumour locations being the thigh and groin areas. Five cases involved recurrent tumours. Clear resection margins were obtained in 15 cases. Autologous vein grafts were preferred over polytetrafluoroethylene (PTFE) prosthesis in 17 cases. A pedicled flap or free flap was required to achieve adequate soft tissue cover in six patients, while the rest underwent primary closure. Five patients lost the patency of the reconstructed vessels with one of these requiring an amputation. The estimated disease-specific survival at 5 years was 58%. Limb-preservation surgery in the context of vessel compromise is not only safe, but also a functionally and psychosocially beneficial means of avoiding an amputation. We believe that careful pre-operative planning and discussion in a multidisciplinary setting is key for obtaining positive outcomes. [ABSTRACT FROM AUTHOR]

Scleromyositis is an autoimmune disease and an overlap syndrome of scleroderma and poly/dermatomyositis. It is characterized by frequent cardiovascular involvement including heart failure, arrhythmias and conduction disturbances. We present a case of a 73-year old female patient who required an upgrade from a DDD pacemaker to cardiac resynchronization therapy due left ventricular dysfunction and permanent ventricular pacing. Electroanatomical mapping (CARTO 3D) revealed extensive right atrial fibrosis which resulted in significant delay in intraatrial conduction. Interval from atrial paced stimulus to A signal in His bundle was 364 ms, while AH and HV intervals were within normal range. [ABSTRACT FROM AUTHOR]

This paper aims to contribute to the definition of ancient rare diseases in skeletons displaying pathologies associated with paralysis. It uses a new suite of methods, which can be applied to challenging cases of possible paralysis in archaeologically-derived human skeletal material, specifically applied to the identification of poliomyelitis. An adult male skeleton from Roman Halbturn, Austria. Morphological and entheseal change analyses, CT scans, X-rays, cross-section morphology, and histology, alongside modern clinical, as well as historic, literature were used to discuss paralyses. The results suggest a diagnosis of poliomyelitis; now considered a rare disease, but perhaps ubiquitous in antiquity, thus complicating the definition of 'rare disease'. The integrated methodological procedures employed for this case constitutes a replicable and thorough approach to diagnosis, and explores the nature of ancient rare diseases. Due to the socio-environmental aspects of poliomyelitis transmission, it is likely that polio was likely not rare in the past. Therefore, the definition of 'rare diseases in the past' must include rarely occurring rarely diagnosed diseases due to biases and challenges within the archaeological and environmental record. The developed suite of methods has not been applied to establish a diagnosis of polio in the past. The individual considered in this study is fairly well-preserved; thus, this set of analyses may not be applicable to all remains where preservation is poor or highly fragmentary, and the discussion of rare diseases requires relatively secure diagnoses and context. Large collections and series of skeletal human remains are recommended to develop definitive conclusions. [ABSTRACT FROM AUTHOR]

Infrared thermography allows the detection of infrared radiation which can be reliably associated with skin temperature. Modern portable thermography devices have been used to identify the location of skin perforators by detecting subtle differences in skin temperature. The aim of this study is to conduct a diagnostic accuracy systematic review to determine the specificity and sensitivity of infrared thermography. A PRISMA-compliant systematic review and meta-analysis was conducted, scrutinising PUBMED and EMBASE databases for diagnostic studies measuring the accuracy of infrared thermography for perforator identification. Article screening, review and data gathering was conducted in parallel by two independent authors. Eligible studies were subject to a formal risk of bias was assessment using the QUADAS2 instrument. A total of 254 entries were obtained, of which 7 satisfied our pre-established inclusion criteria. These studies reported a total of 435 perforators in 133 individuals. The most commonly investigated locations were the antero-lateral thigh and abdominal wall. Reported sensitivity values ranged from 73.7% to 100%. A meta-analysis demonstrated a cumulative sensitivity of 95%. Specificity was not routinely reported. All studies presented a moderate to high risk of bias according to QUADAS2. Affordable infrared thermography devices are an interesting alternative to traditional preoperative investigations for perforator mapping. They are sensitive enough to reliably identify a large proportion of perforators as "hot-spots". However, there is limited evidence to estimate the specificity of this technology, as studies have failed to report true negative values associated with "cold-spots". [ABSTRACT FROM AUTHOR]

The integrity of the intestinal barrier in the diseased is key to prevent further complications and disease such as sepsis and death, whereas, the role of food bioactive molecules (i. e. phenolic compounds (PCs) on the intestinal barrier, is still unknown. The current aim was to explore the benefits of the oral PC administration on the intestinal barrier integrity in animals. The effects of PCs on the intestinal barrier integrity in in vivo animal models of intestinal inflammation were assessed up-to August 2020 from the PubMed, SCOPUS, and Cochrane Library databases under the PRISMA methodology. The risk of bias was assessed from ARRAY and SCYRCLE tools. From 1241 articles, 14 studies were included. In animals, oral resveratrol (n = 6) improves the intestinal barrier integrity and reduces intestinal damage. Additionally, grape seed extract (n = 2), curcumin (n = 1), genistein (n = 1), chlorogenic acid (n = 1), grape pomace (n = 1), olive leaf (n = 1) or cranberry extract (n = 1) improve the intestinal barrier integrity downregulating various inflammatory molecules (TNF-α, and other interleukins), and increasing the antioxidant enzymes in animals. Furthermore, resveratrol, quercetin, epigallocatechin, and other PCs improve the epithelial barrier integrity and pro-inflammatory molecule expression in the intestinal epithelia. The oral PC administration in animals improves the intestinal barrier integrity and function from three main mechanisms: 1) The reduction of pro-inflammatory molecules, 2) the improvement in tight-junction protein expression, and 3) the improvement of the antioxidant intracellular activity suggesting the potential use of PCs in the management of intestinal injury in humans, particularly for resveratrol, the most studied PC. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas arising in the groin and inguinal canal can be difficult to diagnose and manage. This is in part explained by the complex anatomy of the region. Early referral to specialist centres has been advocated, as inadvertent excision of these tumours can jeopardise definitive treatment. We present our 16-year experience at a regional sarcoma service. A retrospective review of patients treated for a sarcoma in the groin and inguinal canal within the North of England Bone and Soft Tissue Tumour Service was performed. Demographic information, along with therapeutic approach and outcomes, was recorded and analysed. A total of 67 patients were identified, out of which 18 presented with new lesions, 32 presented after having a previous inadvertent sarcoma excision, 10 had a planned resection and 7 presented with recurrent disease. Liposarcomas were the most common histological subtype (55%), and the spermatic cord the most common origin (45%). Fifty-seven patients had surgery for this condition, with seven incomplete excision. Regional flaps were used in 60% of the cases, to allow an adequate oncological resection and soft tissue cover. Patients who had undergone a previous inadvertent sarcoma excision did not have worse rates of local recurrence, metastases and disease-specific mortality. Kaplan–Meier disease-specific survival at 5 years was 82%. Inadvertent and inadequate groin sarcoma excision outside of specialist centres remains a problem despite clear guidance. Despite this, an aggressive oncological approach to inadequately managed tumours shows similar outcomes as tumour managed exclusively by our specialist centre. [ABSTRACT FROM AUTHOR]

Wearable inertial measurement units (IMUs) enable gait analysis in the clinic, but require calibrations that may affect subsequent gait measurements. This study assessed concurrent validity and within-session reliability of gait kinematics measured by a frequently calibrated IMU-based system. Calibration pose accuracy and intra-rater repeatability, and IMU orientation tracking accuracy, were additionally quantified. Calibration poses and gait were recorded in 15 women using IMUs and optical motion capture (OMC) (reference standard) simultaneously. Participants performed six consecutive trials: each comprising a calibration pose and a walk. IMU tracking was assessed separately (once-off) using technical static and dynamic tests. Differences of > 5° constituted clinical significance. Concurrent validity for gait revealed clinically significant between-system differences for sagittal angles (root-mean-square error [RMSE] 6.7°–15.0°; bias −9.3°–3.0°) and hip rotation (RMSE 7.9°; bias −4.2°). After removing modelling offsets, differences for all angles (except hip rotation) were < 5°. Gait curves correlated highly between systems (r > 0.8), except hip rotation, pelvic tilt and -obliquity. Within-session reliability of IMU-measured gait angles was clinically acceptable (standard error of measurement [SEM] < 5°). Calibration poses were repeatable (SEM 0.3°–2.2°). Pose accuracy revealed mean absolute differences (MAD) < 5° for all angles except sagittal ankle, hip and pelvis. IMU tracking accuracy demonstrated RMSE ≤ 2.0°. A frequently calibrated IMU system provides reliable gait measurements; comparing highly to OMC after removing modelling differences. Calibration poses can be implemented accurately for most angles and consistently. IMU-measured gait data are clinically useful and comparable within participants, but should not be compared to OMC-measured data. [ABSTRACT FROM AUTHOR]

Early postoperative compression of free flaps for lower limb reconstruction remains controversial. It may reduce venous congestion and promote the resolution of oedema. However, concerns remain regarding inadvertent pedicle compression, which may lead to flap failure. The aim of this systematic review was to determine the safety and effectiveness of this intervention. A systematic review was designed in compliance with PRISMA. MEDLINE and EMBASE databases were searched. Parallel screening, selection of eligible studies, and data gathering were carried out by two independent authors. A formal risk of bias assessment was included along with the appraisal of outcomes. A total of 847 abstracts were retrieved and 262 free flaps for lower limb reconstruction were identified in ten eligible articles. The overall flap failure rate for patients who underwent early postoperative compression was 1.6%. Apart from flap failure rates, there were no other outcomes consistently reported and none of the studies included a no-compression group for comparison. All included studies had methodological flaws, resulting in a high risk of bias. Nevertheless, there was consistent reporting of flap failure as a postoperative outcome. Compression of free flaps in the context of lower limb reconstruction does not appear to be associated with a higher flap failure rate compared with other series. Compression bandages may reduce the pain associated with dangling regimes. However, there is no evidence to support that free flap compression in the context of lower limb reconstruction is associated with any other clinical benefit. [ABSTRACT FROM AUTHOR]

Background: Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1(PD-L1) therapy frequently entails immune-related adverse events (irAEs), and biomarkers to predict irAEs are lacking. Although checkpoint inhibitors have been found to reinvigorate T cells, the relevance of autoantibodies remains elusive.Objective: Our aim was to explore whether IgG autoantibodies directed against coexpressed antigens by tumor tissue and healthy skin correlate with skin irAEs and therapy outcome.Methods: We measured skin-specific IgG via enzyme-linked immunosorbent assay in patients with non-small cell lung cancer (NSCLC) who received anti-PD1/PD-L1 treatment between July 2015 and September 2017 at the Kantonsspital St. Gallen. Sera were sampled at baseline and during therapy after 8 weeks.Results: Analysis of publicly available tumor expression data revealed that NSCLC and skin coexpress BP180, BP230, and type VII collagen. A skin irAE developed in 16 of 40 recruited patients (40%). Only elevated anti-BP180 IgG at baseline significantly correlated with the development of skin irAEs (P = .04), therapy response (P = .01), and overall survival (P = .04).Limitations: The patients were recruited in a single tertiary care center.Conclusions: Our data suggest that the level of anti-BP180 IgG of NSCLC patients at baseline is associated with better therapy response and overall survival and with a higher probability to develop skin irAEs during anti-PD1/PD-L1 treatment. [ABSTRACT FROM AUTHOR]

To determine the effectiveness of the Functional Mobility Assessment (FMA) when measuring an individual's satisfaction with functional mobility. Secondary analysis of cross-sectional self-report data. Assistive technology center within an academic medical center in the Midwestern United States. Individuals with a disability that use or plan to use a mobility device (N=871). Not applicable. FMA. All FMA items (10/10) contributed to a single unidimensional construct with good to strong fit to a unidimensional confirmatory factor model. Rasch analysis revealed that the rating scale, majority of persons (>90%), and all items fit the Rasch measurement model. The FMA demonstrated adequate reliability (person reliability=0.85) and separated persons into 3 strata: those with high, medium, and low satisfaction with functional mobility. The FMA is an appropriate measure for use in research and clinical settings to quantify satisfaction with functional mobility among mobility device users. [ABSTRACT FROM AUTHOR]

Autologous breast reconstruction, on its own, is a complex microsurgical procedure. However, this operation is usually just one of a series of steps along a patient's reconstructive journey. This includes not only a primary major surgical event but also the consequent recovery, potential complications and secondary surgeries required to optimise the final outcome. Unfortunately, there is limited information of what patients can expect from this reconstructive journey in the literature. The aim of this study was to characterise the journey of a consecutive cohort of patients through their whole reconstructive pathway in a high-volume UK-based breast reconstruction service. A retrospective case analysis was undertaken including all the patients who had an autologous breast reconstruction at the Queen Victoria Hospital in East Grinstead between January 2012 and December 2014. Their case notes were reviewed from their initial referral to their final discharge. Number of operations, complication rates and time required to complete their journey were recorded, as well as differences between different flap options, immediate versus delayed and unilateral versus bilateral breast reconstructions. A total of 409 autologous breast reconstruction cases were performed in the 3-year study period. The vast majority of breast reconstructions used a deep inferior epigastric perforator flap (81.5%), with muscle-sparing transverse abdominal flaps (14.6%) and transverse upper gracilis flaps (3.9%) being the other options utilised. Free flap success was observed in 99.5% cases. Almost all patients opted for subsequent surgery (94%) of any kind. Only 75% opted for the reconstruction of their nipples. On average, 3.20 procedures were required per patient on this cohort, and these procedures were performed in 1.5 surgical episodes on average. Bilateral reconstructions reached the discharge point sooner than unilateral reconstructions and required a smaller number of operations. The average time to complete the reconstructive journey was 20.8 months. Patient-centred decision-making is fundamental to select the correct intervention for each patient and empower her in her healing journey. Standard measuring of patient satisfaction is still an unaccomplished goal in our unit. [ABSTRACT FROM AUTHOR]

In this study, a cohort of Ohio pharmacy students were surveyed about knowledge and attitudes regarding medical marijuana (MMJ). Pharmacy educators in legalized states were asked how MMJ education was incorporated into pharmacy curricula. Pharmacy students from six colleges were emailed surveys. Pharmacy educators from 79 colleges in states with legal MMJ programs were emailed regarding curricular content covering MMJ. A total of 319 student respondents received scores between 50 and 60% on knowledge-based questions. Students favored legalization of medical, but not recreational marijuana; they are not confident in ability to counsel; they believe little education on MMJ is provided in pharmacy school; and feel that more education is needed on MMJ. Students supporting MMJ were more likely to support recreational use of marijuana (p < 0.001), and education about MMJ (p < 0.001). Students in advanced years were less willing to dispense medical marijuana (p < 0.01), and less likely to support pharmacist availability for counseling (p < 0.05). Sixty-two percent of colleges who responded to the survey in legalized states provided education on MMJ to pharmacy students. Sixty-four percent of colleges responding who provided MMJ education offered a required course; 84.6% educated on indications and misuse/abuse; 92.3% on side effects, and adverse drug reactions; 53.8% on drug interactions. Ohio pharmacy student knowledge regarding medical marijuana is low. Students believe pharmacists should be available for counseling on MMJ; they feel unprepared to dispense MMJ, and would like more education on MMJ. Some colleges of pharmacy in the US report providing MMJ education; extent is unknown. [ABSTRACT FROM AUTHOR]

Introduction: Facial synkinesis is characterised by abnormal and unintentional co-contractions of facial muscles caused by aberrant facial nerve healing, usually as a sequalae of facial palsy. The aim of this project is to propose a consensus for reporting this condition in the literature to facilitate the conduction of primary and secondary evidence studies, considering that no previous research has inquired in to this matter. Methods: A systematic literature search was performed in MEDLINE and EMBASE databases, considering all the published articles on facial synkinesis. Studies that used a particular measuring system for this condition were included. Two authors independently assessed these articles focusing on the grading instruments utilised. The most commonly used instruments were analysed, and their basic components were incorporated in a modified Delphi survey, which was sent to a panel of experts. Results: The systematic literature search retrieved 502 articles, of which 159 met the inclusion criteria. The two most commonly mentioned instruments were the House–Brackmann Scale and the Sunnybrook Facial Grading System. These were then followed by the Yanagihara scale, the Synkinesis Assessment Questionnaire, the eFace system and the Facial Clinimetric Evaluation. The modified Delphi study concluded that an ideal grading system for facial synkinesis should not only include a clinician-based evaluation of symmetry and signs of synkinesis, but also patient-reported symptoms. Conclusions: Considering the characteristics of the studies found in the literature, the Sunnybrook Facial Grading System fits best with the ideal synkinesis measuring instrument described by the panel of experts. However, in order to satisfy the need to include patient-reported outcomes, the use of the Facial Clinimetric Evaluation as an adjunct to the Sunnybrook Facial Grading System is proposed. [ABSTRACT FROM AUTHOR]

In the isoprenoid biosynthesis pathway, mevalonate is phosphorylated in 2 subsequent enzyme steps by MVK and PMVK to generate mevalonate pyrophosphate that is further metabolized to produce sterol and nonsterol isoprenoids. Biallelic pathogenic variants in MVK result in the autoinflammatory metabolic disorder MVK deficiency. So far, however, no patients with proven PMVK deficiency due to biallelic pathogenic variants in PMVK have been reported. This study reports the first patient with functionally confirmed PMVK deficiency, including the clinical, biochemical, and immunological consequences of a homozygous missense variant in PMVK. The investigators performed whole-exome sequencing and functional studies in cells from a patient who, on clinical and immunological evaluation, was suspected of an autoinflammatory disease. The investigators identified a homozygous PMVK p.Val131Ala (NM_006556.4: c.392T>C) missense variant in the index patient. Pathogenicity was supported by genetic algorithms and modeling analysis and confirmed in patient cells that revealed markedly reduced PMVK enzyme activity due to a virtually complete absence of PMVK protein. Clinically, the patient showed various similarities as well as distinct features compared to patients with MVK deficiency and responded well to therapeutic IL-1 inhibition. This study reported the first patient with proven PMVK deficiency due to a homozygous missense variant in PMVK, leading to an autoinflammatory disease. PMVK deficiency expands the genetic spectrum of systemic autoinflammatory diseases, characterized by recurrent fevers, arthritis, and cytopenia and thus should be included in the differential diagnosis and genetic testing for systemic autoinflammatory diseases. [ABSTRACT FROM AUTHOR]