Cancer Incidence After Diagnosis of Abdominal Aortic Aneurysm-Brief Report.

BACKGROUND: Epidemiological and mechanistic data support a potential causal link between cardiovascular disease (CVD) and cancer. Abdominal aortic aneurysms (AAAs) represent a common form of CVD with at least partially distinct genetic and biologic pathogenesis from other forms of CVD. The risk of cancer and how this risk differs compared with other forms of CVD, is unknown among AAA patients. We conducted a retrospective cohort study using the IBM MarketScan Research Database to test whether individuals with AAA have a higher cancer risk independent of traditional shared risk factors. METHODS: All individuals ≥18 years of age with ≥36 months of continuous coverage between 2008 and 2020 were enrolled. Those with potential Mendelian etiologies of AAA, aortic aneurysm with nonspecific anatomic location, or a cancer diagnosis before the start of follow-up were excluded. A subgroup analysis was performed of individuals having the Health Risk Assessment records including tobacco use and body mass index. The following groups of individuals were compared: (1) with AAA, (2) with non-AAA CVD, and (3) without any CVD. RESULTS: The propensity score-matched cohort included 58 993 individuals with AAA, 117 986 with non-AAA CVD, and 58 993 without CVD. The 5-year cumulative incidence of cancer was 13.1% (12.8%-13.5%) in participants with AAA, 10.1% (9.9%-10.3%) in participants with non-AAA CVD, and 9.6% (9.3%-9.9%) in participants without CVD. Multivariable-adjusted Cox proportional hazards regression models found that patients with AAA exhibited a higher cancer risk than either those with non-AAA CVD (hazard ratio, 1.28 [95% CI, 1.23-1.32]; P<0.001) or those without CVD (hazard ratio, 1.32 [95% CI, 1.26-1.38]; P<0.001). Results remained consistent after excluding common smoking-related cancers and when adjusting for tobacco use and body mass index. CONCLUSIONS: Patients with AAA may have a unique risk of cancer requiring further mechanistic study and investigation of the role of enhanced cancer screening.

Step-Wise Chondrogenesis of Human Induced Pluripotent Stem Cells and Purification Via a Reporter Allele Generated by CRISPR-Cas9 Genome Editing.

The differentiation of human induced pluripotent stem cells (hiPSCs) to prescribed cell fates enables the engineering of patient-specific tissue types, such as hyaline cartilage, for applications in regenerative medicine, disease modeling, and drug screening. In many cases, however, these differentiation approaches are poorly controlled and generate heterogeneous cell populations. Here, we demonstrate cartilaginous matrix production in three unique hiPSC lines using a robust and reproducible differentiation protocol. To purify chondroprogenitors (CPs) produced by this protocol, we engineered a COL2A1-GFP knock-in reporter hiPSC line by CRISPR-Cas9 genome editing. Purified CPs demonstrated an improved chondrogenic capacity compared with unselected populations. The ability to enrich for CPs and generate homogenous matrix without contaminating cell types will be essential for regenerative and disease modeling applications. Stem Cells 2019;37:65-76.

Low mortality rates after endovascular aortic repair expand use to high-risk patients.

OBJECTIVE: The 2010 endovascular aneurysm repair (EVAR) trial 2 (EVAR 2) reported that patients with comorbidity profiles rendering them unfit for open aneurysm repair who underwent EVAR did not experience a survival advantage compared with those who did not undergo intervention. These patients experienced a 30-day mortality of 7.3%, whereas reports from similar cohorts reported far lower mortality rates. The primary objective of our study was to compare the incidence of 30-day mortality in low- and high-risk patients undergoing EVAR in a contemporary data set, using patient risk stratification criteria from EVAR 2. Secondarily, we sought to identify risk factors associated with a disproportionate contribution to 30-day mortality risk. METHODS: Data were obtained from the 2005 to 2013 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data Files (N = 24,813). Patients were included in the high-risk cohort with the presence of renal, respiratory, or cardiac preoperative criteria alone or in combination. Renal impairment criteria were defined as dialysis and creatinine concentration >2.26 mg/dL. Respiratory impairment criteria included history of chronic obstructive pulmonary disease and preoperative ventilator support. Cardiac impairment criteria included history of myocardial infarction, congestive heart failure, angina, and prior coronary intervention. Patient and procedural characteristics and 30-day postoperative outcomes were compared using Pearson χ2 tests for categorical variables and Wilcoxon rank sum tests for continuous variables. RESULTS: Among 24,813 patients undergoing EVAR, 12,043 (48%) patients were characterized as high risk (at least one impairment criterion); 12,770 (52%) patients were stratified as low risk. The 30-day mortality rate was 1.9% in the high-risk cohort compared with the 7.3% reported by EVAR 2, and it was higher in the high-risk cohort compared with the low-risk cohort (1.9% vs 0.9%; P < .001). Whereas the presence of each comorbidity increased the odds of 30-day mortality (respiratory odds ratio [OR], 1.62; 95% confidence interval [CI], 1.16-2.26; P = .005; cardiac OR, 1.55; 95% CI, 1.14-2.10; P = .005), the presence of renal criteria disproportionately increased the odds of mortality threefold (OR, 3.42; 95% CI, 2.31-5.09; P < .001). CONCLUSIONS: Contemporary 30-day mortality after EVAR in high-risk patients is substantially lower than that reported in the EVAR 2 trial. Whereas low- and high-risk stratification by current comorbidity criteria is appropriate, attention needs to be paid to disproportionate risk contribution from renal disease to mortality compared with cardiac and pulmonary comorbidities. Given the lower mortality risk than previously described, patients stratified as high risk should be thoughtfully considered for definitive EVAR.

Therapeutic and prognostic significance of PARP-1 in advanced mycosis fungoides and Sezary syndrome.

While mycosis fungoides (MF) is typically an indolent malignancy, it may infrequently undertake an aggressive course. We used proteomic analyses to identify a biomarker of the aggressive course of MF. Results of this investigation demonstrated that PARP-1, heat-shock protein family A (Hsp70) member 1 like (HSAP1L), Hsp70 member 1A (HSPA1A), ATP-depending RNA helicase (DDX17) and the α-isoform of lamina-associated polypeptide 2 (TMPO) had higher expression in aggressive disease versus non-aggressive. Moreover, PARP-1 was overexpressed in patients with early stage of MF who developed later an aggressive disease. PARP-1 was evaluated as a new target for therapy, demonstrating the selective dose-dependent cytotoxic effect of PARP inhibitors on Sézary cells in comparison with non-malignant lymphocytes. In conclusion, we believe that PARP-1 may serve not only as a biomarker at initial biopsies for a disease that may become aggressive but also as a new therapeutic target of advanced MF and Sézary syndrome.

Laparotomy during endovascular repair of ruptured abdominal aortic aneurysms increases mortality.

OBJECTIVE: Subset analyses from small case series suggest patients requiring laparotomy during endovascular repair of ruptured abdominal aortic aneurysms (REVAR) have worse survival than those undergoing REVAR without laparotomy. Most concomitant laparotomies are performed for abdominal compartment syndrome. This study used data from the American College of Surgeons National Surgical Quality Improvement Program to determine whether the need for laparotomy during REVAR is associated with increased mortality. METHODS: Data were obtained from the 2005 to 2013 National Surgical Quality Improvement Program participant user files based on Current Procedural Terminology (American Medical Association, Chicago, Ill) and International Classification of Diseases-9 Edition coding. Patient and procedure-related characteristics and 30-day postoperative outcomes were compared using Pearson χ2 tests for categoric variables and Wilcoxon rank sum tests for continuous variables. A backward-stepwise multivariable logistic regression model was used to identify patient- and procedure-related factors associated with increased death after REVAR. RESULTS: We identified 1241 patients who underwent REVAR, and 91 (7.3%) required concomitant laparotomy. The 30-day mortality was 60% in the laparotomy group and 21% in the standard REVAR group (P < .001). The major complication rate was also higher in the laparotomy group (88% vs 63%; P < .001). Multivariable analysis showed laparotomy was strongly associated with 30-day mortality (odds ratio, 5.91; 95% confidence interval, 3.62-9.62; P < .001). CONCLUSIONS: Laparotomy during REVAR is a commonly used technique for the management of elevated intra-abdominal pressure and abdominal compartment syndrome development. The results of this study strongly confirm findings from smaller studies that the need for laparotomy during REVAR is associated with significantly worse 30-day survival.

Perioperative Optimization of Geriatric Lower Extremity Bypass in the Era of Increased Performance Accountability.

BACKGROUND: The initiation of bundled payment for care improvement by Centers for Medicare and Medicaid Services (CMS) has led to increased financial and performance accountability. As most vascular surgery patients are elderly and reimbursed via CMS, improving their outcomes will be critical for durable financial stability. As a first step in forming a multidisciplinary pathway for the elderly vascular patients, we sought to identify modifiable perioperative variables in geriatric patients undergoing lower extremity bypass (LEB). METHODS: The 2011-2013 LEB-targeted American College of Surgeons National Surgical Quality Improvement Program database was used for this analysis (n = 5316). Patients were stratified by age <65 (n = 2171), 65-74 (n = 1858), 75-84 (n = 1190), and ≥85 (n = 394) years. Comparisons of patient- and procedure-related characteristics and 30-day postoperative outcomes stratified by age groups were performed with Pearson χ2 tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. RESULTS: During the study period, 5316 total patients were identified. There were 2171 patients aged <65 years, 1858 patients in the 65-74 years age group, 1190 patients in the 75-84 years age group, and 394 patients in the ≥85 years age group. Increasing age was associated with an increased frequency of cardiopulmonary disease (P < 0.001) and a decreased frequency of diabetes, tobacco use, and prior surgical intervention (P < 0.001). Only 79% and 68% of all patients were on antiplatelet and statin therapies, respectively. Critical limb ischemia occurred more frequently in older patients (P < 0.001). Length of hospital stay, transfusion requirements, and discharge to a skilled nursing facility increased with age (P < 0.001). Thirty-day amputation rates did not differ significantly with age (P = 0.12). CONCLUSIONS: Geriatric patients undergoing LEB have unique and potentially modifiable perioperative factors that may improve postoperative outcomes. These modifiers will be the basis of a multidisciplinary care path targeting the geriatric vascular surgery patients.

Clinical assessment of the sensory ataxias; diagnostic algorithm with illustrative cases.

Ataxia is a common neurological syndrome resulting from cerebellar, vestibular or sensory disorders. The recognition and characterisation of sensory ataxia remains a challenge. Cerebellar ataxia is the more common and easier to identify; sensory ataxia is often mistaken for cerebellar ataxia, leading to diagnostic errors and delays. A coherent aetiological work-up is only possible if clinicians initially recognise sensory ataxia. We discuss ways to separate sensory from cerebellar ataxia, the causes of sensory ataxia and the clinico-neurophysiological syndromes causing the sensory ataxia syndromes. We summarise a logical tiered approach as a diagnostic algorithm.

Efferocytosis in atherosclerosis.

Cardiovascular disease is the leading cause of death worldwide, and it commonly results from atherosclerotic plaque progression. One of the increasingly recognized drivers of atherosclerosis is dysfunctional efferocytosis, a homeostatic mechanism responsible for the clearance of dead cells and the resolution of inflammation. In atherosclerosis, the capacity of phagocytes to participate in efferocytosis is hampered, leading to the accumulation of apoptotic and necrotic tissue within the plaque, which results in enlargement of the necrotic core, increased luminal stenosis and plaque inflammation, and predisposition to plaque rupture or erosion. In this Review, we describe the different forms of programmed cell death that can occur in the atherosclerotic plaque and highlight the efferocytic machinery that is normally implicated in cardiovascular physiology. We then discuss the mechanisms by which efferocytosis fails in atherosclerosis and other cardiovascular and cardiometabolic diseases, including myocardial infarction and diabetes mellitus, and discuss therapeutic approaches that might reverse this pathological process.

Introducing a new proforma for the safe use of intraoperative tourniquets in orthopaedic surgery.

INTRODUCTION: The routine use of pneumatic tourniquets in orthopaedic surgery is widely adopted in current practice; however, practice varies considerably based mainly on anecdotal and cultural traditions. This Quality Improvement Project evaluated current service as per the newly published British Orthopaedic Association Standards for Trauma & Orthopaedics guideline on 'The Safe Use of Intraoperative Tourniquets'. METHODS: Patient records were reviewed retrospectively for all patients who underwent orthopaedic surgery in September 2021 at one NHS hospital trust. Simultaneously, a nine-question survey was distributed to the orthopaedic teams allowing assessment of non-quantifiable aspects of the guidelines. The results were delivered as a local presentation, and trust-wide dissemination of posters using the mnemonic 'PRESSURE' was used to educate staff. The quantitative audit was repeated twice, after this intervention (March 2022) and after the advent of a new electronic patient record system with an online proforma (January 2023). RESULTS: There was significant improvement (p<0.05) in all aspects of tourniquet documentation between the audit cycles. Maximum advised tourniquet duration was exceeded in <2% of cases regardless of guideline publication. Recommended pressures were used in less than one-third of cases in all audit cycles, with no significant change throughout. More than 50% of respondents sized their tourniquet on 'whatever looked best fit'. CONCLUSIONS: Despite tourniquet usage being part of the UK Trauma & Orthopaedic Surgery curriculum, this study is the first to highlight a lack of compliance with 'gold standard' guidelines and the need for increased training for staff to ensure patients are exposed to the safest possible environment. Although electronic proformas can aid recording of information, the limitation to change is cultural tradition and anecdotal experience.

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Photoacoustic imaging has sufficient penetration and sensitivity to map and characterize human atherosclerotic plaque. Here, near infrared photoacoustic imaging is shown to detect plaque components and, when combined with ultrasound imaging, to differentiate stable and vulnerable plaque. In an ex vivo study of photoacoustic imaging of excised plaque from 25 patients, 88.2% sensitivity and 71.4% specificity were achieved using a clinically-relevant protocol. In order to determine the origin of the near-infrared auto-photoacoustic (NIRAPA) signal, immunohistochemistry, spatial transcriptomics and proteomics were applied to adjacent sections of the plaque. The highest NIRAPA signal was spatially correlated with bilirubin and associated blood-based residue and inflammatory macrophages bearing CD74, HLA-DR, CD14 and CD163 markers. In summary, we establish the potential to apply the NIRAPA-ultrasound imaging combination to detect vulnerable carotid plaque.

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Here, near-infrared auto-photoacoustic (NIRAPA) imaging is shown to detect plaque components and, when combined with ultrasound imaging, to differentiate stable and vulnerable plaque. In an ex vivo study of photoacoustic imaging of excised plaque from 25 patients, 88.2% sensitivity and 71.4% specificity were achieved using a clinically-relevant protocol. In order to determine the origin of the NIRAPA signal, immunohistochemistry, spatial transcriptomics and spatial proteomics were co-registered with imaging and applied to adjacent plaque sections. The highest NIRAPA signal was spatially correlated with bilirubin and associated blood-based residue and with the cytoplasmic contents of inflammatory macrophages bearing CD74, HLA-DR, CD14 and CD163 markers. In summary, we establish the potential to apply the NIRAPA-ultrasound imaging combination to detect vulnerable carotid plaque and a methodology for fusing molecular imaging with spatial transcriptomic and proteomic methods.

Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle functions.

Rbfox RNA binding proteins are implicated as regulators of phylogenetically-conserved alternative splicing events important for muscle function. To investigate the function of rbfox genes, we used morpholino-mediated knockdown of muscle-expressed rbfox1l and rbfox2 in zebrafish embryos. Single and double morphant embryos exhibited changes in splicing of overlapping sets of bioinformatically-predicted rbfox target exons, many of which exhibit a muscle-enriched splicing pattern that is conserved in vertebrates. Thus, conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated alternative splicing. Morphology and development of single morphant embryos were strikingly normal; however, muscle development in double morphants was severely disrupted. Defects in cardiac muscle were marked by reduced heart rate and in skeletal muscle by complete paralysis. The predominance of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibril assembly is defective and disorganized in double morphants. Ultra-structural analysis revealed that although sarcomeres with electron dense M- and Z-bands are present in muscle fibers of rbfox1l/rbox2 morphants, they are substantially reduced in number and alignment. Importantly, splicing changes and morphological defects were rescued by expression of morpholino-resistant rbfox cDNA. Additionally, a target-blocking MO complementary to a single UGCAUG motif adjacent to an rbfox target exon of fxr1 inhibited inclusion in a similar manner to rbfox knockdown, providing evidence that Rbfox regulates the splicing of target exons via direct binding to intronic regulatory motifs. We conclude that Rbfox proteins regulate an alternative splicing program essential for vertebrate heart and skeletal muscle functions.

Renal allograft recipients fail to increase interferon-γ during invasive fungal diseases.

Invasive fungal diseases are a major cause of death in renal allograft recipients. We previously reported that adjunctive recombinant human interferon-γ therapy has clinical utility for invasive fungal diseases after renal transplantation. We have now developed a rapid peripheral blood-based quantitative real-time PCR assay that enables accurate profiling of cytokine imbalances. Our preliminary studies in renal transplant patients with invasive fungal diseases suggest that they fail to mount an adequate interferon-γ response to the fungal infection. In addition, they have reduced IL-10 and increased TNF-α when compared to stable renal transplant patients. These preliminary cytokine profiling-based observations provide a possible explanation for the therapeutic benefit of adjunctive human interferon-γ therapy in renal allograft recipients with invasive fungal diseases.

Systematic review and meta-analysis of management of incompetent perforators in patients with chronic venous insufficiency.

OBJECTIVE: Incompetent perforator veins (IPVs) contribute to venous pathology and are surgically treated based on hemodynamic measurements, size, and the CEAP (Clinical, Etiological, Anatomical, and Pathophysiological) classification. The objective of the present study was to systematically review and synthesize the current literature regarding the surgical management of IPVs, including open ligation, subfascial endoscopic perforator surgery (SEPS), endovascular laser ablation, ultrasound-guided sclerotherapy, and radiofrequency ablation. METHODS: English-language literature reported before November 2021 was reviewed from the PubMed, EMBASE, and MEDLINE databases for primary studies reporting safety and efficacy outcomes in the surgical treatment of IPVs. Study quality and risk of bias were assessed using the Cochrane risk of bias tool for comparative studies and a modified version of the Newcastle-Ottawa scale for noncomparative studies. A random effects model was used to pool the effect sizes for efficacy outcomes of wound healing and freedom from wound recurrence. RESULTS: A total of 81 studies were included for qualitative synthesis, representing 7010 patients, with a mean age of 54.7 years. The overall evidence quality was low to intermediate, with a moderate to high risk of bias in the comparative studies. An 11.3% complication rate was found across the interventions, with no reported incidence of stroke or air embolism. Regarding efficacy, the pooled estimates for short-term (≤1 year) wound healing were 99.9% for ultrasound-guided sclerotherapy (95% confidence interval [CI], 0.81%-1%), 72.2% for open ligation (95% CI, 0.04%-0.94%), and 96.0% for SEPS (95% CI, 0.79%-0.99%). For short-term freedom from wound recurrence, the pooled estimate for SEPS was 91.0% (95% CI, 0.3%-0.99%). CONCLUSIONS: The current evidence regarding the treatment of IPVs is limited owing to the low adherence to reporting standards in the observational studies and the lack of randomization, blinding, and allocation concealment in the comparative studies. Additional comparative studies are needed to guide clinical decision-making regarding the invasive treatment options for IPVs.

Dynamic changes in chromatin accessibility are associated with the atherogenic transitioning of vascular smooth muscle cells.

AIMS: De-differentiation and activation of pro-inflammatory pathways are key transitions vascular smooth muscle cells (SMCs) make during atherogenesis. Here, we explored the upstream regulators of this 'atherogenic transition'. METHODS AND RESULTS: Genome-wide sequencing studies, including Assay for Transposase-Accessible Chromatin using sequencing and RNA-seq, were performed on cells isolated from both murine SMC-lineage-tracing models of atherosclerosis and human atherosclerotic lesions. At the bulk level, alterations in chromatin accessibility were associated with the atherogenic transitioning of lesional SMCs, especially in relation to genes that govern differentiation status and complement-dependent inflammation. Using computational biology, we observed that a transcription factor previously related to coronary artery disease, Activating transcription factor 3 (ATF3), was predicted to be an upstream regulator of genes altered during the transition. At the single-cell level, our results indicated that ATF3 is a key repressor of SMC transitioning towards the subset of cells that promote vascular inflammation by activating the complement cascade. The expression of ATF3 and complement component C3 was negatively correlated in SMCs from human atherosclerotic lesions, suggesting translational relevance. Phenome-wide association studies indicated that genetic variation that results in reduced expression of ATF3 is correlated with an increased risk for atherosclerosis, and the expression of ATF3 was significantly down-regulated in humans with advanced vascular disease. CONCLUSION: Our study indicates that the plasticity of atherosclerotic SMCs may in part be explained by dynamic changes in their chromatin architecture, which in turn may contribute to their maladaptive response to inflammation-induced stress.

Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy.

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of 'covert' virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.

The treatment of Dupuytren disease.

The treatment of progressive Dupuytren contractures has historically been and continues to be largely surgical. Although a number of surgical interventions do exist, limited palmar fasciectomy continues to be the most common and widely accepted treatment option. Until recently, nonsurgical options were limited and clinically ineffective. However, the commercial availability and recent approval of collagenase clostridium histolyticum now provides practitioners with a nonsurgical approach to this disease. This article presents a comprehensive review of the surgical and nonsurgical treatments of Dupuytren disease, with a focus on collagenase.

Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses.

The immune response to HIV-1 in patients who carry human histocompatibility leukocyte antigen (HLA)-B27 is characterized by an immunodominant response to an epitope in p24 gag (amino acids 263-272, KRWIILGLNK). Substitution of lysine (K) or glycine (G) for arginine (R) at HIV-1 gag residue 264 (R264K and R264G) results in epitopes that bind to HLA-B27 poorly. We have detected a R264K mutation in four patients carrying HLA-B27. In three of these patients the mutation occurred late, coinciding with disease progression. In another it occurred within 1 yr of infection and was associated with a virus of syncytium-inducing phenotype. In each case, R264K was tightly associated with a leucine to methionine change at residue 268. After the loss of the cytotoxic T lymphocyte (CTL) response to this epitope and in the presence of high viral load, reversion to wild-type sequence was observed. In a fifth patient, a R264G mutation was detected when HIV-1 disease progressed. Its occurrence was associated with a glutamic acid to aspartic acid mutation at residue 260. Phylogenetic analyses indicated that these substitutions emerged under natural selection rather than by genetic drift or linkage. Outgrowth of CTL escape viruses required high viral loads and additional, possibly compensatory, mutations in the gag protein.

Exogenous interferon-gamma immunotherapy for invasive fungal infections in kidney transplant patients.

The incidence of invasive fungal infections (IFIs) in nonneutropenic solid organ transplant patients is increasing. We report our clinical experience with the use of interferon-gamma (IFN-gamma) immunotherapy in seven renal transplant patients who developed life threatening, disseminated IFIs refractory to conventional antifungal drug therapy. The infections were all microbiologically and histologically proven. The rapid cure of these disseminated infections with exogenous IFN-gamma injections was not associated with impaired kidney allograft function despite the use of liposomal amphotericin B in all cases. No clinical toxicity from the IFN-gamma immunotherapy was seen and no IFI relapsed during long-term follow-up. Our experience is both uncontrolled and in patients with unpredictable fungal infection-related outcomes. However, compared to standard approaches, the accelerated cure of life threatening, disseminated IFIs with 6 weeks of combination antifungal drug therapy and IFN-gamma immunotherapy saved lives, retained allograft function and led to substantial cost savings in this small patient group.

Failed distal biceps tendon repair using a single-incision EndoButton technique and its successful treatment: case report.

Surgical repair has become a mainstay in the treatment of ruptures of the distal biceps tendon and multiple surgical techniques have been described advocating anatomic or near-anatomic repair. Fixation with an EndoButton technique has been shown to have superior fixation strength and durable clinical outcomes. Here, we describe a case of failed EndoButton fixation of the distal biceps tendon, and its successful treatment.