Although intravenous administration of contrast media may trigger a variety of adverse reactions, sedated patients undergoing computed tomography (CT) scanning usually are not able to report their symptoms, which may delay detection of adverse reactions. Furthermore, changes in vital signs cannot be typically measured during mobile CT scanning, which worsens the situation. We aimed to characterize contrast-related hemodynamic changes that occur during mobile CT scanning and predict sudden hypotension based on subtle but robust changes in the electrocardiogram (ECG). We analyzed the digitized hemodynamic data of 20 consecutive patients who underwent clipping of a cerebral artery aneurysm and contrast-enhanced CT scanning following the surgical procedure. Hemodynamic variables, including ECG findings, invasive blood pressure (BP), pulse oximetry results, capnography findings, cardiac output, and systemic vascular resistance, were monitored simultaneously. We measured morphological changes in ECG-derived parameters, including the R–R interval, ST height, and QRS R-amplitude, on a beat-to-beat basis, and evaluated the correlation between those parameters and hemodynamic changes. After the radiocontrast injection, systolic BP decreased by a median 53 mmHg from baseline and spontaneously recovered after 63 ± 19 s. An increase in QRS R-amplitude (median 0.43 mV) occurred 25 ± 10 s before hypotension developed. The receiver operating characteristic curve showed that a 16% increase in QRS R-amplitude can predict a decrease in systolic BP of >25% (area under the curve 0.852). Increased cardiac output (median delta 2.7 L/min from baseline) and decreased systemic vascular resistance (median delta 857 dyn·s/cm⁵ from baseline) were also observed during hypotension. During mobile CT scanning, profound but transient hypotension can be observed, associated with decreased vascular resistance. Augmentation of QRS R-amplitude from an ECG represents a sensitive surrogate for onset of a hypotensive episode after contrast injection, thereby serving as a simple and continuous noninvasive hemodynamic monitoring tool. Full article

The areas in which Stromal Vascular Fraction cells (SVFs) have been used include radiotherapy based tissue damage after mastectomy, breast augmentation, calvarial defects, Crohn’s fistulas, and damaged skeletal muscle. Currently, the authors present their experience using regenerative cell therapy in breast reconstruction. The goal of this study was to evaluate the safety and efficacy of the use of Engineered Fat Graft Enhanced with Adipose-derived Stromal Vascular Fraction cells (EF-e-A) in breast reconstruction. 121 patients that were affected by the outcomes of breast oncoplastic surgery were treated with EF-e-A, comparing the results with the control group (n = 50) treated with not enhanced fat graft (EF-ne-A). The preoperative evaluation included a complete clinical examination, a photographic assessment, biopsy, magnetic resonance (MRI) of the soft tissue, and ultrasound (US). Postoperative follow-up took place at two, seven, 15, 21, 36 weeks, and then annually. In 72.8% (n = 88) of breast reconstruction treated with EF-e-A, we observed a restoration of the breast contour and an increase of 12.8 mm in the three-dimensional volume after 12 weeks, which was only observed in 27.3% (n = 33) of patients in the control group that was treated with EF-ne-A. Transplanted fat tissue reabsorption was analyzed with instrumental MRI and US. Volumetric persistence in the study group was higher (70.8%) than that in the control group (41.4%) (p < 0.0001 vs. control group). The use of EF-e-A was safe and effective in this series of treated cases. Full article

Purpose: We aimed to study clinical and radiological outcomes of conversion from hemiarthroplasty to Charnley hip replacement (CHR) with a particular concern over reported increased dislocation rate and literature review. Conversion of hip hemiarthroplasty to total hip replacement (THR) is a procedure reported to have high rates of complications. In the literature, there is no specific study on small head conversion. The purpose of this study was to evaluate the conversion of failed hip hemiarthroplasty to CHR with the use of modern implants. Methods: The study included 42 patients, who underwent the above procedure. The operations were carried out using a modern Charnley-type THR with a 22-mm diameter of femoral head and a trans-trochanteric approach. The mean follow-up was 75.7 months (range 25–171). Radiographs from the last follow up were evaluated for loosening and other reasons of failure. Clinical outcome was assessed using postoperative pain, function scores, complications and implant survivorship as well as radiological evaluation. Charnley’s modified pain and mobility scoring system were used for clinical and Hodgkinson and Harris’ criteria were used for radiological assessment. Results: Functionally, all of the patients showed improvement. Mean improvement in the pain level was by average of 2.4. On mobility assessment, 38 patients (90.4%) improved. Three patients (7.1%) had recurrent infections and three (4.8%) cases were treated with revision surgery and pseudarthrosis. Further complications occurred in 19.1%, not requiring operative treatment. On radiological evaluation, one (2.4%) case showed cup demarcation without bone loss, two (4.8%) cup migration, and one (2.4%) stem demarcation. Kaplan Meier survival analysis showed a survival of 90% at 96 months of follow up (95% CI (confidence interval), 60–90). Conclusion: Larger head might not be the answer to decrease the dislocation rate. Complication rates during revision of hip hemiarthroplasty to modern CHR with 22.225-mm head diameter were comparable to first-time THR revision despite having a smaller head. Full article

Studies are extremely limited for the investigation of the clinical outcome of da Vinci robot-assisted bilateral internal mammary artery (BIMA) grafting in coronary artery bypass grafting (CABG) surgery. This study aimed to explore the short-term outcome of da Vinci robot-assisted BIMA grafting through the left pleural space. Relevant data were collected from patients with multi-vessel coronary artery disease receiving two kinds of CABG: a group of patients receiving da Vinci robot-assisted CABG with BIMA grafting, and another group of patients receiving sternotomy CABG with BIMA grafting. Primary endpoints, which included cardiovascular and renal endpoints, were analyzed between the groups using the chi-square test, analysis of variance test, and Kaplan–Meier analysis. Compared with the conventional group (n = 22), the robotic group (n = 22) had a significantly longer operation time (12.7 ± 1.7 vs. 8.5 ± 1.5 hours; p < 0.01) and a marginally lower mean of serum creatinine at baseline (1.2 ± 0.3 vs. 2.0 ± 1.7 mg/dL; p = 0.04). Primary endpoints (5, 22.7% vs. 12, 54.5%; p = 0.03) and renal endpoints (1, 4.5% vs. 7, 31.8%; p = 0.02) at six months were significantly reduced in the robotic group compared with the conventional group. There were no differences in cardiovascular endpoints at six months between the groups (1, 4.5% vs. 0; p = 1.00). The data showed that da Vinci robot-assisted BIMA grafting was safe, with equal cardiovascular events and lowered renal events at six months, as compared to conventional sternotomy BIMA grafting, despite the longer procedure time. The short-term study suggests that da Vinci robot-assisted BIMA grafting may be considered a favorable surgical option for patients with severe coronary artery disease. Full article

The aim of our study was to investigate the association between global spinal alignment, spinopelvic parameters, and outcomes of osteoporotic vertebral compression fractures (OVCF). Patients with vertebral compression fractures seen at our hospital between October 2017 and November of 2018 with a bone mineral density (BMD) T-score < −2.5 were recruited for the study. Surgical intervention was performed after eight weeks of conservative treatment depending on clinical symptoms and the willingness of patients. Spinopelvic and sagittal alignment parameters were compared between patients who had surgery and those that did not. Seventy-nine patients were included in the study. Twenty-five patients (31.6%, mean age: 73.28 ± 9.78 years) received surgery, and 54 (68.3%, mean age: 73 ± 8.58 years) conservative treatment only. Pelvic tilt, pelvic incidence, and local kyphotic angle were statistically different between the groups (all p < 0.05). A sagittal vertical axis ≥ 50 mm, distance between the C7 plumb line and the center of the fractured vertebra (DSVA) ≥ 60 mm, pelvic incidence outside of the range of 44 to 62°), and pelvic tilt ≥ 27° were associted with the need for surgical intervention. Measurement of spinopelvic parameters can predict the need for surgery in patients with OVCF. Full article

Hyperphosphatemia is commonly present in end-stage renal disease. Klotho (KL) is implicated in phosphate homeostasis since it acts as obligate co-receptor for the fibroblast growth factor 23 (FGF23), a major phosphaturic hormone. We hypothesized that genetic variation in the KL gene might be associated with alterations in phosphate homeostasis resulting in hyperphosphatemia. We performed sequencing for determining KL gene variants in a group of resistant hyperphosphatemic dialysis patients. In a 67-year-old female, blood DNA sequencing revealed a heterozygous deletion of a T at position 1041 (c.1041delT) in exon 2. This variation caused a frameshift with substitution of isoleucine for phenylalanine and introduction of a premature termination codon (p.Ile348Phefs*28). cDNA sequencing showed absence of deletion-carrier transcripts in peripheral blood mononuclear cells suggesting degradation of these through a nonsense-mediated RNA decay pathway. Experiments in vitro showed that p.Ile348Phefs*28 variant impaired FGF23 signaling pathway, indicating a functional inactivation of the gene. In the patient, serum levels of KL were 2.9-fold lower than the mean level of a group of matched dialysis subjects, suggesting a compromise in the circulating protein concentration due to haploinsufficiency. These findings provide a new loss-of-function variant in the human KL gene, suggesting that genetic determinants might be associated to clinical resistant hyperphosphatemia. Full article

The current standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early-stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information on early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB-approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early-stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cell-free DNA (cfDNA), methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (high versus low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6–99.3%) and 94.1% (95% CI: 82.3–100%). In addition, in patients with normal renal function (estimated glomerular filtration rate (eGFR) ≥ 90), the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be detected by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function. Full article

We aimed to investigate operating conditions, postoperative pain, and overall satisfaction of surgeons using deep neuromuscular blockade (NMB) vs. no NMB in patients undergoing lumbar spinal surgery under general anesthesia. Eighty-three patients undergoing lumbar fusion were randomly assigned to receive deep NMB (n = 43) or no NMB (n = 40). In the deep-NMB group, rocuronium was administered to maintain deep NMB (train-of-four count 0, post-tetanic count 1–2) until the end of surgery. In the no-NMB group, sugammadex 4 mg/kg at train-of-four (TOF) count 0–1 or sugammadex 2 mg/kg at TOF count ≥2 was administered to reverse the NMB 10 min after placing the patient prone. Peak inspiratory airway pressure, plateau airway pressure, lumbar retractor pressure significantly were lower in the deep-NMB group. Degree of surgical field bleeding (0–5), muscle tone (1–3), and satisfaction (1–10) rated by the surgeon were all superior in the deep-NMB group. Pain scores, rescue fentanyl consumption in post-anesthesia care unit (PACU), and postoperative patient-controlled analgesia consumption were significantly lower in the deep-NMB group, and this group had a shorter length of stay in PACU. Compared to no NMB, deep NMB provides better operating conditions, reduced postoperative pain and higher overall satisfaction in lumbar spinal surgery. Full article

Mesenchymal stem cells (MSCs) are becoming an increasingly popular therapeutic option among patients with a broad range of ailments to modulate immunity and induce regeneration. The majority of patients receiving these MSC therapies are on concurrent medication or have ongoing infection. In the present study, we examined the effect of immunosuppressive drugs and lipopolysaccharides (LPS)/endotoxins on the secretory profile, migration towards site of injury, and suppression of lymphocyte proliferation of bone marrow-derived MSCs (BMSCs). Generally, LPS coculture augmented the secretory capacity of BMSCs while exposure to immunosuppressive drugs resulted primarily in no change or attenuated secretion, with some cases of increased secretion, dependent on the cytokine assayed. Among the immunosuppressants evaluated, Hydrocortisone had the most widespread inhibitory effect, while LPS from E. coli O111:B4 had the most potent stimulatory effect. In addition, we also showed that Hydrocortisone or LPS from E. coli O111:B4 affected the migratory and immunosuppressive capacity of BMSCs. Following simulation with Hydrocortisone, BMSC migration was attenuated, and immunosuppressive capacity against T cell proliferation was enhanced, however, the opposite effects were seen with LPS from E. coli O111:B4. Our data suggests that the clinical outcomes of MSC-based therapy are affected by the use of immunosuppressive medication or the presence of endotoxemia in patients. Full article

Previous studies showed that transcutaneous vagus nerve stimulation (tVNS) modulates the autonomic nervous system (ANS) in resting condition. However, the autonomic regulation in response to an orthostatic challenge during tVNS in healthy subjects remains unknown. We tested the hypothesis that tVNS reduces heart rate (HR) and alters the responsivity of ANS to orthostatic stress in healthy subjects. In a randomized and cross-over trial, thirteen healthy subjects underwent two experimental sessions on different days: (1) tVNS and (2) control. Using a tVNS device, an auricular electrode was placed on the left cymba conchae of the external ear; an electric current with a pulse frequency of 25 Hz and amplitude between 1 and 6 mA was applied. For the assessment of ANS, the beat-to-beat HR and systolic arterial pressure (SAP) were analyzed using linear and nonlinear approaches during clinostatic and orthostatic conditions. In clinostatic conditions, tVNS reduced HR (p < 0.01), SAP variability (p < 0.01), and cardiac and peripheral sympathetic modulation (p < 0.01). The responsivity of the peripheral sympathetic modulation to orthostatic stress during tVNS was significantly higher when compared to the control session (p = 0.03). In conclusion, tVNS reduces the HR and affects cardiac and peripheral autonomic control and increases the responses of peripheral autonomic control to orthostatic stress in healthy subjects. Full article

The lymphatic network is well known for its role in the maintenance of tissue fluid homeostasis, absorption of dietary lipids, trafficking of immune cells, and adaptive immunity. Aberrant lymphatic function has been linked to lymphedema and immune disorders for a long time. Discovery of lymphatic cell markers, novel insights into developmental and postnatal lymphangiogenesis, development of genetic mouse models, and the introduction of new imaging techniques have improved our understanding of lymphatic function in both health and disease, especially in the last decade. Previous studies linked the lymphatic vasculature to atherosclerosis through regulation of immune responses, reverse cholesterol transport, and inflammation. Despite extensive research, many aspects of the lymphatic circulation in atherosclerosis are still unknown and future studies are required to confirm that arterial lymphangiogenesis truly represents a therapeutic target in patients with cardiovascular disease. In this review article, we provide an overview of factors and mechanisms that regulate lymphangiogenesis, summarize recent findings on the role of lymphatics in macrophage reverse cholesterol transport, immune cell trafficking and pathogenesis of atherosclerosis, and present an overview of pharmacological and genetic strategies to modulate lymphatic vessel density in cardiovascular tissue. Full article

Recent studies have shown that body composition is an important factor that affects surgical site infection (SSI). However, each study has utilized different body composition criteria. Therefore, in this study, we aim to determine the most predictable body composition criteria for the prediction of SSI after gastrectomy. The visceral fat area (VFA), subcutaneous fat area (SFA), and muscle area were assessed by a preoperative-stage computed tomographic (CT) scan. To compare the predictive performance of body composition for SSI, logistic regression models were used, and the models were compared using the receiver operation characteristic (ROC) curve and the area under the curve (AUC) value. Of the 1038 eligible patients, 58 patients (5.6%) developed SSI. The VFA-to-SFA ratio showed the best predictive performance (mean AUC 75.11). The cutoff value for the SSI of the VFA-to-SFA ratio was 0.94, and the sensitivity and specificity were 67.86% and 77.65%, respectively. A multivariate logistic analysis indicated that a total gastrectomy (OR, 2.13; p = 0.017), stage III or IV cancer (OR, 2.66; p = 0.003), and a high VFA-to-SFA ratio (OR, 8.09; p < 0.001) were independent risk factors for SSI after gastrectomy. The VFA-to-SFA ratio is the most predictable body composition model for use in predicting the incidence of SSI after gastrectomy. Full article

Healthcare expenditures in the United States are growing at an alarming level with the Centers for Medicare and Medicaid Services (CMS) projecting that they will reach $5.7 trillion per year by 2026. Inflammatory diseases and related syndromes are growing in prevalence among Western societies. This growing population that affects close to 60 million people in the U.S. places a significant burden on the healthcare system. Characterized by relatively slow development, these diseases and syndromes prove challenging to diagnose, leading to delayed treatment against the backdrop of inevitable disability progression. Patients require healthcare attention but are initially hidden from clinician’s view by the seemingly generalized, non-specific symptoms. It is imperative to identify and manage these underlying conditions to slow disease progression and reduce the likelihood that costly comorbidities will develop. Enhanced diagnostic criteria coupled with additional technological innovation to identify inflammatory conditions earlier is necessary and in the best interest of all healthcare stakeholders. The current total cost to the U.S. healthcare system is at least $90B dollars annually. Through unique analysis of financial cost drivers, this review identifies opportunities to improve clinical outcomes and help control these disease-related costs by 20% or more. Full article

We aimed to assess national trends in the rates of diabetes-related potentially preventable hospitalizations (overall and by preventable condition) in the total adult population of Spain. We performed a population-based study of all adult patients with diabetes who were hospitalized from 1997 to 2015. Overall potentially preventable hospitalizations and hospitalizations by diabetes-related preventable conditions (short-term complications, long-term complications, uncontrolled diabetes, and lower-extremity amputations) were examined. Annual rates adjusted for age and sex were analyzed and trends were calculated. Over 19-years-period, 424,874 diabetes-related potentially preventable hospitalizations were recorded. Overall diabetes-related potentially preventable hospitalizations decreased significantly, with an average annual percentage change of 5.1 (95%CI: −5.6–(−4.7%); p_trend < 0.001). Among preventable conditions, the greatest decrease was observed in uncontrolled diabetes (−5.6%; 95%CI: −6.7–(−4.7%); p_trend < 0.001), followed by short-term complications (−5.4%; 95%CI: −6.1–(−4.9%); p_trend < 0.001), long-term complications (−4.6%; 95%CI: −5.1–(−3.9%); p_trend < 0.001), and lower-extremity amputations (−1.9%; 95%CI: −3.0–(−1.3%); p_trend < 0.001). These reductions were observed in all age strata for overall DM-related PPH and by preventable condition but lower-extremity amputations for those <65 years old. There was a greater reduction in overall DM-related PPH, uncontrolled DM, long-term-complications, and lower extremity amputations in females than in males (all p < 0.01). No significant difference was shown for short-term complications (p = 0.101). Our study shows a significant reduction in national trends for diabetes-related potentially preventable hospitalizations in Spain. These findings could suggest a sustained improvement in diabetes care in Spain, despite the burden of these diabetes-related complications and the increase in the diabetes mellitus prevalence. Full article

A retrospective review was performed to assess the risk factors and outcomes of BK virus infection and nephropathy (BKVN), an early complication in pediatric kidney allograft recipients. The study investigated the incidence, risk factors, and clinical outcomes of BK viremia and BKVN in a Korean population of pediatric patients who received renal transplantation from 2001–2015 at the Seoul National University Hospital. BKVN was defined as biopsy-proven BKVN or plasma BK viral loads >10,000 copies/mL for >3 weeks. BK viremia was defined as a BK viral load >100 copies/mL in blood. Among 168 patients assessed for BK virus status, 30 patients (17.9%) tested positive for BK viremia at a median of 12.6 months after transplantation. BKVN was diagnosed in six patients (3.6%) at a median of 13.4 months after transplantation. Three of the six BKVN patients had Alport syndrome (p = 0.003), despite this disease comprising only 6% of the study population. Every patient with BK viremia and Alport syndrome developed BKVN, while only 11.1% of patients with BK viremia progressed to BKVN in the absence of Alport syndrome. Multivariate analysis revealed that Alport syndrome was associated with BKVN development (hazard ratio 13.2, p = 0.002). BKVN treatment included the reduction of immunosuppression, leflunomide, and intravenous immunoglobulin. No allografts were lost in the two years following the diagnosis of BKVN. In summary, the incidence of BKVN in pediatric kidney allograft recipients was similar to findings in previous reports, but was higher in patients with underlying Alport syndrome. Full article