Novel Strategies in Transplantation: Genetic Engineering and Vascularized Composite Allotransplantation.

INTRODUCTION: Despite the clinical success in vascularized composite allotransplantation (VCA), systemic immunosuppression remains necessary to prevent allograft rejection. Even with potent immunosuppressive regimens (tacrolimus, mycophenolate mofetil, and steroids), most patients experience several rejection episodes, often within the same year. The risk of systemic side effects must constantly be weighed against the risk of under-immunosuppression and, thus, acute and chronic rejection. In this context, genomic editing has emerged as a potential tool to minimize the need for toxic immunosuppressive regimens and has gained attention in the fields of solid organ transplantation and xenotransplantation. This strategy may also be relevant for the future of VCA. METHODS: We discuss the topic of genetic engineering and review recent developments in this field that justify investigating tools such as clustered regularly interspaced short palindromic repeats/Cas9 in the context of VCA. RESULTS: We propose specific strategies for VCA based on the most recent gene expression data. This includes the well-known strategy of tolerance induction. Specifically, targeting the interaction between antigen-presenting cells and recipient-derived T cells by CD40 knockout may be effective. The novelty for VCA is a discovery that donor-derived T lymphocytes may play a special role in allograft rejection of facial transplants. We suggest targeting these cells prior to transplantation (e.g., by ex vivo perfusion of the transplant) by knocking out genes necessary for the long-term persistence of donor-derived immune cells in the allograft. CONCLUSION: Despite the demonstrated feasibility of VCA in recent years, continued improvements to immunomodulatory strategies using tools like clustered regularly interspaced short palindromic repeats/Cas9 could lead to the development of approaches that mitigate the limitations associated with rejection of this life-giving procedure.

Tolerance Induction in Vascularized Composite Allotransplantation-A Brief Review of Preclinical Models.

Pre-clinical studies are an obligatory tool to develop and translate novel therapeutic strategies into clinical practice. Acute and chronic rejection mediated by the recipient's immune system remains an important limiting factor for the (long-term) survival of vascularized composite allografts (VCA). Furthermore, high intensity immunosuppressive (IS) protocols are needed to mitigate the immediate and long-term effects of rejection. These IS regiments can have significant side-effects such as predisposing transplant recipients to infections, organ dysfunction and malignancies. To overcome these problems, tolerance induction has been proposed as one strategy to reduce the intensity of IS protocols and to thereby mitigate long-term effects of allograft rejection. In this review article, we provide an overview about animal models and strategies that have been used to induce tolerance. The induction of donor-specific tolerance was achieved in preclinical animal models and clinical translation may help improve short and long-term outcomes in VCAs in the future.

National Trends in Microtia Repair Cost and Hospital Length of Stay.

Microtia can have deleterious impacts on the functional, psychological, and aesthetic outcomes of affected young children. Reconstructive procedures can alleviate these negative outcomes and significantly improve the quality of life for patients; however, the cost and length of hospital stay (LOS) for such procedures and the factors that impact them have not been well-characterized. This study seeks to understand the hospital-level (institution type, size, and geographic region) and patient-level factors (race, age, and insurance status) that impact cost and LOS in patients who undergo microtia reconstructive surgery. A retrospective data analysis was conducted utilizing the National Inpatient Sample (NIS) database for the years 2008 to 2015. Inclusion criteria included patients who had an International Classification of Diseases, Ninth Revision (ICD-9) diagnostic code for microtia (744.23) as well as a procedure for microtia correction (186×/187×). A total of 714 microtia repair cases met the inclusion criteria and were sampled from the NIS database. Microtia repair cost was significantly increased on the West Coast compared with the Northeast ($34,947 versus $29,222, P =0.020), increased with patient age ($614/y, P =0.012), and gradually increased from 2008 to 2015 ($25,897-$48,985, P <0.001). Microtia LOS was significantly increased with government-controlled hospitals compared with private hospitals (1.93 versus 1.39 d, P =0.005), increased with patients on Medicaid compared with private insurance (2.33 versus 2.00 d, P =0.036), and overall decreased with patient age (-0.07 d/y, P =0.001). The results not only identify the multifactorial impacts that drive cost and LOS in microtia repair but provide insights into the financial and medical considerations patients and their families must navigate.

Assessment of Sex Diversity Among Craniofacial Academic Faculty.

Sex diversity among plastic surgery and its subspecialties faculties lags behind many medical specialties. Despite the significant evidence in favor of diversity in leadership, female presence in high-ranking positions in medicine is lacking across multiple specialties. In this study, we aim to evaluate sex disparity among faculty across craniofacial fellowship programs by comparing the disparities among total number of faculty, program directors, years in practice, and academic rank. Our sample included 354 individuals including 193 craniofacial surgery journal editorial board members, 130 craniofacial surgery academic faculty members, and 31 craniofacial surgery association board members. A significant difference (P-value <0.0001) was seen among male and female craniofacial surgery faculty with 84.6% males. Faculty members were further subdivided by academic rank. A significant difference was found between the number of male and female faculty members at all academic positions (P-value =0.043). Of 41 full professors, 2.4% were female. There were 42 associate professors queried with 14.3% female. Similarly, 43 assistant professors were identified with 32.0% female. Years in practice after completing terminal training were analyzed across the academic faculty. There was a significant difference in the number of male and female faculty members across all experience levels (P-value =0.0037). Among the faculty with <10 years since completion of terminal training, 32.4 % were female. For faculty with 10 to 20 years after post-terminal training, 19.6% were female. For those with 20 to 30 years of experience, 0% were female. Finally, for the faculty with over 30 years since graduation, 5.9% were female. Board membership in 2 craniofacial surgery organizations was analyzed: the American Cleft Palate-Craniofacial Association and the American Society of Maxillofacial Surgeons. Among the 17 board members of the American Cleft Palate-Craniofacial Association, 8 (47.1%) were female. For the American Society of Maxillofacial Surgeons, 5 (35.7%) were female. Data were collected for 193 editorial board members from 2 craniofacial surgery journals. There was a significant difference between the number of male and female members across both journals (χ2 value: 33.3570; P-value <0.0001). Among 56 editorial board members from Cleft Palate-Craniofacial Journal, 26 (46.4%) members were female. In comparison, Journal of Craniofacial Surgery has 24.8% female editorial board members. Sex diversity among faculty members is really important and should be brought into light to highlight and improve areas of particular importance and of tremendous potential impact. Given our results, surgical residencies and fellowship programs should begin to show concrete commitment and increase their efforts to recruit and retain a diverse faculty not only for the educational benefit but more importantly to achieve a higher level of care for all.

An update on long-term mental health in eight face transplant recipients - A single center experience.

OBJECTIVE: Face transplantation is a groundbreaking and complex surgical intervention offering profound physical and psychological benefits to patients with severe facial disfigurements. This report provides an update on the long-term psychosocial outcome of eight face transplant recipients. METHOD: All transplant recipients were initially transplanted at Brigham and Women´s Hospital (Boston, USA) between 2011 and 2020 and are seen as outpatient patients at Yale New Haven Hospital (New Haven, USA). A mixed-methods approach was used to assess the psychological well-being of these patients. The Short-Form 12, Brief-COPE, EQ-VAS and CES-D were administered between October 2022 and October 2023. RESULTS: Older age of face transplant recipients was significantly and positively associated with better mental health and increased use of both emotional and instrumental support (Brief-COPE). The initial enhancement in patients' self-reported quality of life, as assessed by the EQVAS, declined on the EQ-VAS score at the last follow-up period. Similarly, an increase in depression score was observed (CES-D score) up through the last follow-up assessment. Both of the latter results, however, did not reach statistical significance. CONCLUSIONS: These results underscore the importance of ongoing psychological support throughout the long-term journey of recovery for face transplant recipients. They emphasized the need for a comprehensive, patient-centered approach that also addresses the complex psychological dimensions and contributes to our understanding of the mental health dynamics involved in face transplantation, underscoring the need for guidelines and continued research in this evolving field.

Biosynthetic Origin of Formylaminooxyvinylglycine and Characterization of the Formyltransferase GvgI.

4-Formylaminooxyvinylglycine (FVG) is an herbicidal and antibacterial nonproteinogenic amino acid produced by several strains of the Pseudomonas fluorescens species complex. It contains a unique vinyl alkoxyamine moiety with an O-N bond, and its biosynthetic origin remains unknown. Here, we show that the gvg cluster from P. fluorescens WH6 is responsible for the biosynthesis of FVG and two additional O-N bond-containing oxyvinylglycines, guanidinooxyvinylglycine and aminooxyvinylglycine. Feeding studies in the producing bacteria indicate that these compounds originate from homoserine. We identify a formyltransferase gvgI that is required for the production of FVG and characterize the activity of this enzyme in vitro toward amino acids with a side chain amine. Sequence similarity network analysis reveals that GvgI and homologues make up a distinct group from the main classes of formyltransferases.

Phytostabilization of acidic mine tailings with biochar, biosolids, lime, and locally-effective microbes: Do amendment mixtures influence plant growth, tailing chemistry, and microbial composition?

Abandoned mine lands present persistent environmental challenges to ecosystems and economies; reclamation an important step for overcoming these challenges. Phytostabilization is an elegant and cost-effective reclamation strategy, however, establishing plants on severely degraded soils is problematic, often requiring soil amendment additions. We evaluated whether amendment mixtures composed of lime, biochar, biosolids, and locally effective microbes (LEM) could alleviate the constraints that hinder phytostabilization success. We hypothesized that 1) plants grown in tailings amended with lime, biochar, and biosolids (LBB) would establish faster and grow larger than plants grown in tailings amended with lime only, and 2) the LEM source would influence microbial community function and structure in amended mine tailings. We conducted a greenhouse study that simulated in situ conditions to measure the influence of LBB-LEM amendment blends on plant growth, plant nutrients, metal concentrations, microbial function, and microbial community structure. Blue wildrye [Elymus glaucus Buckley ssp. Jepsonii (Burtt Davy) Gould] was grown in tailings collected from the Formosa mine site amended with various combinations of LBB-LEM. The above and below ground biomass of plants grown in mine tailings amended with LBB was 3 to 4 times larger than the biomass of plants grown in tailings amended only with lime. Although the LEM addition did not influence immediate plant growth, it did affect nutrient content and altered the rhizosphere community membership. As such, it is not yet clear if LEM-driven alterations in microbial membership will advance mine reclamation strategies by improving long-term growth.

Hand injuries in sports - a retrospective analysis of 364 cases.

BACKGROUND: Hand injuries are common in sports and associated with high dropout rates and costs. Hence, efforts should strive for further risk prevention measures in order to increase safety in sports. This implies knowledge of sports injury risk profiles. So far, major surveillance programs exist mainly in Anglo-American countries, reflecting the specific concerns of sports in this part of the world. Data on sports injuries within Europe are scarce. As sports behaviour appears to vary demographically, we hypothesised that risk injury profiles differ as well. METHODS: To assess whether the described sports injuries of the hand are applicable to the German population, we performed a five-year retrospective, single-centre analysis of sports-related hand injuries, using data from the Enterprise Clinical Research Data Warehouse of the Hannover Medical School. RESULTS: Notable differences in comparison to other data were observed. Ball sports, cycling and equestrian sports caused most of the recorded hand injuries, which were predominantly fractures of the wrist and hand. Hand injuries in equestrian sports were associated with significantly higher operation and hospitalisation rates as well as a significantly longer inpatient treatment. CONCLUSION: Risk profiles for sports-related hand injuries appear to differ not only in terms of age- and sex, but also geographically. Nation- and Europe-wide hand trauma registries as well as a broad registry participation are necessary in order to accurately assess the risk patterns in Europe; henceforth reducing hand injuries and their sequelae.

Comparative genome structure, secondary metabolite, and effector coding capacity across Cochliobolus pathogens.

The genomes of five Cochliobolus heterostrophus strains, two Cochliobolus sativus strains, three additional Cochliobolus species (Cochliobolus victoriae, Cochliobolus carbonum, Cochliobolus miyabeanus), and closely related Setosphaeria turcica were sequenced at the Joint Genome Institute (JGI). The datasets were used to identify SNPs between strains and species, unique genomic regions, core secondary metabolism genes, and small secreted protein (SSP) candidate effector encoding genes with a view towards pinpointing structural elements and gene content associated with specificity of these closely related fungi to different cereal hosts. Whole-genome alignment shows that three to five percent of each genome differs between strains of the same species, while a quarter of each genome differs between species. On average, SNP counts among field isolates of the same C. heterostrophus species are more than 25× higher than those between inbred lines and 50× lower than SNPs between Cochliobolus species. The suites of nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and SSP-encoding genes are astoundingly diverse among species but remarkably conserved among isolates of the same species, whether inbred or field strains, except for defining examples that map to unique genomic regions. Functional analysis of several strain-unique PKSs and NRPSs reveal a strong correlation with a role in virulence.

Solution NMR structures of Pyrenophora tritici-repentis ToxB and its inactive homolog reveal potential determinants of toxin activity.

Pyrenophora tritici-repentis Ptr ToxB (ToxB) is a proteinaceous host-selective toxin produced by Pyrenophora tritici-repentis (P. tritici-repentis), a plant pathogenic fungus that causes the disease tan spot of wheat. One feature that distinguishes ToxB from other host-selective toxins is that it has naturally occurring homologs in non-pathogenic P. tritici-repentis isolates that lack toxic activity. There are no high-resolution structures for any of the ToxB homologs, or for any protein with >30% sequence identity, and therefore what underlies activity remains an open question. Here, we present the NMR structures of ToxB and its inactive homolog Ptr toxb. Both proteins adopt a ß-sandwich fold comprising three strands in each half that are bridged together by two disulfide bonds. The inactive toxb, however, shows higher flexibility localized to the sequence-divergent ß-sandwich half. The absence of toxic activity is attributed to a more open structure in the vicinity of one disulfide bond, higher flexibility, and residue differences in an exposed loop that likely impacts interaction with putative targets. We propose that activity is regulated by perturbations in a putative active site loop and changes in dynamics distant from the site of activity. Interestingly, the new structures identify AvrPiz-t, a secreted avirulence protein produced by the rice blast fungus, as a structural homolog to ToxB. This homology suggests that fungal proteins involved in either disease susceptibility such as ToxB or resistance such as AvrPiz-t may have a common evolutionary origin.

Persistence of the Host-Selective Toxin Ptr ToxB in the Apoplast.

The necrotrophic fungus Pyrenophora tritici-repentis is responsible for the disease tan spot of wheat. Ptr ToxB (ToxB), a proteinaceous host-selective toxin, is one of the effectors secreted by P. tritici-repentis. ToxB induces chlorosis in toxin-sensitive wheat cultivars and displays characteristics common to apoplastic effectors. We addressed the hypothesis that ToxB exerts its activity extracellularly. Our data indicate that hydraulic pressure applied in the apoplast following ToxB infiltration can displace ToxB-induced symptoms. In addition, treatment with a proteolytic cocktail following toxin infiltration results in reduction of symptom development and indicates that ToxB requires at least 8 h in planta to induce maximum symptom development. In vitro assays demonstrate that apoplastic fluids extracted from toxin-sensitive and -insensitive wheat cultivars cannot degrade ToxB. Additionally, ToxB can be reisolated from apoplastic fluid after toxin infiltration. Furthermore, localization studies of fluorescently labeled ToxB indicate that the toxin remains in the apoplast in toxin-sensitive and -insensitive wheat cultivars. Our findings support the hypothesis that ToxB acts as an extracellular effector.

Renin and aldosterone measurements in the management of arterial hypertension.

Renin-angiotensin-aldosterone system (RAAS) is recognized as the main regulatory system of hemodynamics in man, and its derangements have a key role in the development and maintenance of arterial hypertension. Classification of the hypertensive states according to different patterns of renin and aldosterone levels ("RAAS profiling") allows the diagnosis of specific forms of secondary hypertension and may identify distinct hemodynamic subsets in essential hypertension. In this review, we summarize the application of RAAS profiling for the diagnostic assessment of hypertensive patients and discuss how the pathophysiological framework provided by RAAS profiling may guide therapeutic decision-making, especially in the context of uncontrolled hypertension not responding to multi-therapy.

Expression of GBGT1 is epigenetically regulated by DNA methylation in ovarian cancer cells.

BACKGROUND: The GBGT1 gene encodes the globoside alpha-1,3-N-acetylgalactosaminyltransferase 1. This enzyme catalyzes the last step in the multi-step biosynthesis of the Forssman (Fs) antigen, a pentaglycosyl ceramide of the globo series glycosphingolipids. While differential GBGT1 mRNA expression has been observed in a variety of human tissues being highest in placenta and ovary, the expression of GBGT1 and the genes encoding the glycosyltransferases and glycosidases involved in the biosynthesis of Fs as well as the possible involvement of DNA methylation in transcriptional regulation of GBGT1 expression have not yet been investigated. RESULTS: RT-qPCR profiling showed high GBGT1 expression in normal ovary surface epithelial (HOSE) cell lines and low GBGT1 expression in all (e.g. A2780, SKOV3) except one (OVCAR3) investigated ovarian cancer cell lines, a finding that was confirmed by Western blot analysis. Hierarchical cluster analysis showed that GBGT1 was even the most variably expressed gene of Fs biosynthesis-relevant glycogenes and among the investigated cell lines, whereas NAGA which encodes the alpha-N-acetylgalactosaminidase hydrolyzing Fs was not differentially expressed. Bisulfite- and COBRA-analysis of the CpG island methylation status in the GBGT1 promoter region demonstrated high or intermediate levels of GBGT1 DNA methylation in all ovarian cancer cell lines (except for OVCAR3) but marginal levels of DNA methylation in the two HOSE cell lines. The extent of DNA methylation inversely correlated with GBGT1 mRNA and protein expression. Bioinformatic analysis of GBGT1 in The Cancer Genome Atlas ovarian cancer dataset demonstrated that this inverse correlation was also found in primary ovarian cancer tissue samples confirming our cell line-based findings. Restoration of GBGT1 mRNA and protein expression in low GBGT1-expressing A2780 cells was achieved by 5-aza-2'-deoxycytidine treatment and these treated cells exhibited increased helix pomatia agglutinin-staining, reflecting the elevated presence of Fs disaccharide on these cells. CONCLUSIONS: GBGT1 expression is epigenetically silenced through promoter hypermethylation in ovarian cancer. Our findings not only suggest an involvement of DNA methylation in the synthesis of Fs antigen but may also explain earlier studies showing differential GBGT1 expression in various human tissue samples and disease stages.

The microtubule-depolymerizing agent ansamitocin P3 programs dendritic cells toward enhanced anti-tumor immunity.

In addition to direct tumor cell cytotoxicity, chemotherapy can mediate tumor reduction through immune modulation of the tumor microenvironment to promote anti-tumor immunity. Mature dendritic cells (DCs) play key roles in priming robust immune responses in tumor-bearing hosts. Here, we screened a panel of 21 anticancer agents with defined molecular targets for their ability to induce direct maturation of DCs. We identified ansamitocin P3, a microtubule-depolymerizing agent, as a potent inducer of phenotypic and functional maturation of DCs. Exposure of both murine spleen-derived and human monocyte-derived DCs to ansamitocin P3 triggered up-regulation of maturation markers and production of pro-inflammatory cytokines, resulting in an enhanced T cell stimulatory capacity. Local administration of ansamitocin P3 induced maturation of skin Langerhans cells in vivo and promoted antigen uptake and extensive homing of tumor-resident DCs to tumor-draining lymph nodes. When used as an adjuvant in a specific vaccination approach, ansamitocin P3 dramatically increased activation of antigen-specific T cells. Finally, we demonstrate that ansamitocin P3, due to its immunomodulatory properties, acts in synergy with antibody-mediated blockade of the T cell inhibitory receptors PD-1 and CTLA-4. The combination treatment was most effective and induced durable growth inhibition of established tumors. Mechanistically, we observed a reduced regulatory T cell frequency and improved T cell effector function at the tumor site. Taken together, our study unravels an immune-based anti-tumor mechanism exploited by microtubule-depolymerizing agents, including ansamitocin P3, and paves the way for future clinical trials combining this class of agents with immunotherapy.

Metagenome-assembled genomes of an acid-tolerant nitrifying bacterial community isolated from a bioreactor used in ammonium scrubbers at animal-rearing facilities.

We report 12 metagenome-assembled genomes (MAGS) of a bioreactor community of acid-tolerant nitrifying bacteria. The MAGS include autotrophs in the Nitrospira genus and heterotrophs in the Xanthomonadales, Ktedonobacterales, Cytophagales, Burkholderiales, and Hyphomicrobiales. These taxonomic and genomic data provide insights into the core community members required for nitrification at low pH.

Preclinical Performance of the Combined Application of Two Robotic Systems in Microsurgery: A Two-center Study.

Background: Recent advancements in the development of robotic devices increasingly draw the attention toward the concept of robotic microsurgery, as several systems tailored to open microsurgery are being introduced. This study describes the combined application of a novel microsurgical robot, the Symani, with a novel robotic microscope, the RoboticScope, for the performance of microvascular anastomoses in a two-center preclinical trial. Methods: Six novices, residents, and experienced microsurgeons (n = 18) performed five anastomoses on 1.0-mm-diameter silicone vessels with a conventional versus combined robotic approach, resulting in 180 anastomoses. Microsurgical performance was evaluated, analyzing surgical time, subjective satisfaction with the anastomosis and robotic setup, anastomosis quality using the anastomosis lapse index score, microsurgical skills using the Structured Assessment of Microsurgery Skills score, and surgical ergonomics using the Rapid Entire Body Assessment score. Results: All participants significantly improved their performance during the trial and quickly adapted to the novel systems. Surgical time significantly decreased, whereas satisfaction with the anastomosis and setup improved over time. The use of robotic systems was associated with fewer microsurgical errors and enhanced anastomosis quality. Especially novices demonstrated accelerated skill acquisition upon robotic assistance compared with conventional microsurgery. Moreover, upper extremity positioning was significantly improved. Overall, the robotic approach was subjectively preferred by participants. Conclusions: The concept of robotic microsurgery holds great potential to improve precision and ergonomics in microsurgery. This two-center trial provides promising evidence for a steep learning curve upon introduction of robotic microsurgery systems, suggesting further pursuit of their clinical integration.

Understanding Epidemiological Trends in Geriatric Burn Injuries: A National Multicenter Analysis from NEISS 2004-2022.

Burn injuries pose a significant source of patient morbidity/mortality and reconstructive challenges for burn surgeons, especially in vulnerable populations such as geriatric patients. Our study aims to provide new insights into burn epidemiology by analyzing the largest national, multicenter sample of geriatric patients to date. Utilizing the National Electronic Injury and Surveillance System (NEISS) database (2004-2022), individuals with a "Burn" diagnosis were extracted and divided into two comparison age groups of 18-64 and 65+. Variables including sex, race, affected body part, incident location, burn etiology, and clinical outcomes were assessed between the two groups utilizing two proportion z-tests. 60,581 adult patients who sustained burns were identified from the NEISS database with 6,630 of those patients categorized as geriatric (65+). Geriatric patients had a significantly greater frequency of scald burns (36.9% vs. 35.4%; p<0.01), and third degree/full-thickness burns (10.4% vs 5.5%, p<0.01) relative to non-geriatric adult patients with most of these burns occurring at home (75.9% vs 67.4%; p<0.01). The top five burn sites for geriatric patients were the hand, face, foot, lower arm, and lower leg and the top five burn injury sources were hot water, cookware, oven/ranges, home fires, and gasoline. Geriatric patients had over two times greater risk of hospital admission (OR: 2.32, 95% CI: 2.17-2.49, p<0.01) and over five times greater risk of ED mortality (OR: 6.22, 95% CI: 4.00-9.66, p<0.01) after incurring burn injuries. These results highlight the need for stronger awareness of preventative measures for geriatric burn injuries.

A Nationwide Analysis on Major Upper Extremity Amputations and Replantations.

BACKGROUND: The loss of an upper extremity is a severely disabling condition made medically challenging by the limited window for replantation. This study aims to investigate the burden of traumatic major upper extremity amputations in the United States and uncover possibilities for improvements in treatment. METHODS: The Healthcare Cost and Utilization Project's National Inpatient Sample was screened for International Classification of Diseases-9/10 diagnosis/procedure codes for traumatic and nontraumatic major upper extremity amputations and replantations within the years 2008 to 2017. The resulting pool of cases was analyzed for multiple variables, including level of injury, patient demographics, hospital type and location, length of stay, costs, comorbidities, and complications. RESULTS: A total of 15 155 major upper extremity amputations were recorded, of which 15.20% (n = 2305) were traumatic amputations-almost half of them related to the upper arm (49.6%; P = .0002). The great majority of replantations, however, was conducted at the lower arm level (87.4%; P < .0001), with an overall replantation rate of 22.3%. Nontraumatic amputations were overall associated with significantly higher burden of comorbidities relative to traumatic amputations except for long-term alcohol use (P < .0001). Both, amputations and replantations, were predominantly treated in large urban teaching hospitals, and were significantly more likely to occur in white men. The Southern region of the United States was handling the highest proportion of amputations in the United States, but had the lowest likelihood of replantation. CONCLUSION: This study provides an overview of the national trends in major traumatic upper extremity amputations and replantations, revealing potential health care shortcomings.

Golimumab improves health-related quality of life of patients with moderate-to-severe ulcerative colitis: Results of the go-care study.

BACKGROUND: In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy. METHODS: We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment). RESULTS: Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48. CONCLUSIONS: GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.

From standard therapies to monoclonal antibodies and immune checkpoint inhibitors - an update for reconstructive surgeons on common oncological cases.

Malignancies represent a persisting worldwide health burden. Tumor treatment is commonly based on surgical and/or non-surgical therapies. In the recent decade, novel non-surgical treatment strategies involving monoclonal antibodies (mAB) and immune checkpoint inhibitors (ICI) have been successfully incorporated into standard treatment algorithms. Such emerging therapy concepts have demonstrated improved complete remission rates and prolonged progression-free survival compared to conventional chemotherapies. However, the in-toto surgical tumor resection followed by reconstructive surgery oftentimes remains the only curative therapy. Breast cancer (BC), skin cancer (SC), head and neck cancer (HNC), and sarcoma amongst other cancer entities commonly require reconstructive surgery to restore form, aesthetics, and functionality. Understanding the basic principles, strengths, and limitations of mAB and ICI as (neo-) adjuvant therapies and treatment alternatives for resectable or unresectable tumors is paramount for optimized surgical therapy planning. Yet, there is a scarcity of studies that condense the current body of literature on mAB and ICI for BC, SC, HNC, and sarcoma. This knowledge gap may result in suboptimal treatment planning, ultimately impairing patient outcomes. Herein, we aim to summarize the current translational endeavors focusing on mAB and ICI. This line of research may serve as an evidence-based fundament to guide targeted therapy and optimize interdisciplinary anti-cancer strategies.