PD-L1 (22C3) Expression Correlates with Clinical and Molecular Features of Lung Adenocarcinomas in Cytological Samples.

INTRODUCTION: PD-L1 expression is the most widely used predictive marker for immune checkpoint inhibitor (ICI) therapy in patients with lung adenocarcinoma. However, the current understanding of the association between PD-L1 expression and treatment response is suboptimal. A significant percentage of patients have only a cytological specimen available for clinical management. Therefore, it is relevant to examine the impact of molecular features on PD-L1 expression in cytological samples and how it might correlate with a therapeutic response. METHODS: We evaluated patients diagnosed with adenocarcinoma of the lung who had both in-house targeted next-generation sequencing analysis and paired PD-L1 (22C3) immunohistochemical staining performed on the same cell blocks. We explored the association between molecular features and PD-L1 expression. In patients who underwent ICIs therapy, we assessed how a specific gene mutation impacted a therapeutic response. RESULTS: 145 patients with lung adenocarcinoma were included in this study. PD-L1-high expression was found to be more common in pleural fluid than in other sample sites. Regional lymph node samples showed a higher proportion of PD-L1-high expression (29%) compared with lung samples (6%). The predictive value of PD-L1 expression was retained in cytological samples. Mutations in KRAS were also associated with a PD-L1-high expression. However, tumors with TP53 or KRAS mutations showed a lower therapy response rate regardless of the PD-L1 expression. CONCLUSION: Cytological samples maintain a predictive value for PD-L1 expression in patients with lung adenocarcinoma as regards the benefit of ICI treatment. Specific molecular alterations additionally impact PD-L1 expression and its predictive value.

Aromatase inhibition increases blood pressure and markers of renal injury in female rats.

Aromatase is a monooxygenase that catalyzes the rate-limiting step of estrogen biosynthesis from androgens. Aromatase inhibitors are widely used for the treatment of patients with hormone receptor-positive breast cancer. However, the effects of aromatase inhibitors on cardiovascular and renal health in females are understudied. Given that estrogen is protective against cardiovascular and kidney diseases, we hypothesized that aromatase inhibition elevates blood pressure and induces kidney injury in female Sprague-Dawley rats. Twelve-week-old female rats were implanted with radiotelemetry transmitters to continuously monitor blood pressure. After baseline blood pressure recording, rats were randomly assigned to treatment with the aromatase inhibitor anastrozole (ASZ) or vehicle (Veh) in drinking water. Twenty days after treatment initiation, rats were shifted from a normal-salt (NS) diet to a high-salt (HS) diet for an additional 40 days. Rats were euthanized 60 days after treatment initiation. Body weight increased in both groups over the study period, but the increase was greater in the ASZ-treated group than in the Veh-treated group. Mean arterial pressure increased in ASZ-treated rats during the NS and HS diet phases but remained unchanged in Veh-treated rats. In addition, urinary excretion of albumin and kidney injury marker-1 and plasma urea were increased in response to aromatase inhibition. Furthermore, histological assessment revealed that ASZ treatment increased morphological evidence of renal tubular injury and proximal tubular brush border loss. In conclusion, chronic aromatase inhibition in vivo with ASZ increases blood pressure and markers of renal proximal tubular injury in female Sprague-Dawley rats, suggesting an important role for aromatization in the maintenance cardiovascular and renal health in females.NEW & NOTEWORTHY Aromatase enzyme catalyzes the rate-limiting step in estrogen biosynthesis. Aromatase inhibitors are clinically used for the treatment of patients with breast cancer; however, the impact of inhibiting aromatization on blood pressure and renal function is incompletely understood. The present findings demonstrate that systemic anastrozole treatment increases blood pressure and renal tubular injury markers in female rats fed a high-salt diet, suggesting an important role for aromatization in preserving cardiovascular and renal health in females.

Hydroxyproline stimulates inflammation and reprograms macrophage signaling in a rat kidney stone model.

Meals rich in oxalate are associated with calcium oxalate (CaOx) kidney stone disease. Hydroxy-L-proline (HLP) is an oxalate precursor found in milk and collagen-containing foods. HLP has been shown to induce CaOx crystal formation in rodents. The purpose of this study was to evaluate the effect of HLP induced oxalate levels on inflammation and renal leukocytes during crystal formation. Male Sprague-Dawley rats (6-8 weeks old) were fed a control diet containing no oxalate for 3 days before being randomized to continue the control diet or 5% HLP for up to 28 days. Blood, 24 h urine, and kidneys were collected on Days 0, 7, 14, or 28. Urinary oxalate levels, crystal deposition, and renal macrophage markers were evaluated using ion chromatography-mass spectrometry, immunohistochemistry, and qRT-PCR. Renal leukocytes were assessed using flow cytometry and RNA-sequencing. HLP feeding increased urinary oxalate levels and renal crystal formation in animals within 7 days. HLP also increased renal macrophage populations on Days 14 and 28. Transcriptome analysis revealed that renal macrophages from animals fed HLP for 7 days were involved in inflammatory response and disease, stress response to LPS, oxidative stress, and immune cell trafficking. Renal macrophages isolated on Day 14 were involved in cell-mediated immunological pathways, ion homeostasis, and inflammatory response. Collectively, these findings suggest that HLP-mediated oxalate levels induce markers of inflammation, leukocyte populations, and reprograms signaling pathways in macrophages in a time-dependent manner. Additional studies investigating the significance of oxalate on renal macrophages could aid in our understanding of kidney stone formation.

Podocyte specific deletion of PKM2 ameliorates LPS-induced podocyte injury through beta-catenin.

BACKGROUND: Acute kidney injury (AKI) is associated with a severe decline in kidney function caused by abnormalities within the podocytes' glomerular matrix. Recently, AKI has been linked to alterations in glycolysis and the activity of glycolytic enzymes, including pyruvate kinase M2 (PKM2). However, the contribution of this enzyme to AKI remains largely unexplored. METHODS: Cre-loxP technology was used to examine the effects of PKM2 specific deletion in podocytes on the activation status of key signaling pathways involved in the pathophysiology of AKI by lipopolysaccharides (LPS). In addition, we used lentiviral shRNA to generate murine podocytes deficient in PKM2 and investigated the molecular mechanisms mediating PKM2 actions in vitro. RESULTS: Specific PKM2 deletion in podocytes ameliorated LPS-induced protein excretion and alleviated LPS-induced alterations in blood urea nitrogen and serum albumin levels. In addition, PKM2 deletion in podocytes alleviated LPS-induced structural and morphological alterations to the tubules and to the brush borders. At the molecular level, PKM2 deficiency in podocytes suppressed LPS-induced inflammation and apoptosis. In vitro, PKM2 knockdown in murine podocytes diminished LPS-induced apoptosis. These effects were concomitant with a reduction in LPS-induced activation of ß-catenin and the loss of Wilms' Tumor 1 (WT1) and nephrin. Notably, the overexpression of a constitutively active mutant of ß-catenin abolished the protective effect of PKM2 knockdown. Conversely, PKM2 knockdown cells reconstituted with the phosphotyrosine binding-deficient PKM2 mutant (K433E) recapitulated the effect of PKM2 depletion on LPS-induced apoptosis, ß-catenin activation, and reduction in WT1 expression. CONCLUSIONS: Taken together, our data demonstrates that PKM2 plays a key role in podocyte injury and suggests that targetting PKM2 in podocytes could serve as a promising therapeutic strategy for AKI. TRIAL REGISTRATION: Not applicable. Video abstract.

Lupus nephritis correlates with B cell interferon-ß, anti-Smith, and anti-DNA: a retrospective study.

BACKGROUND: In systemic lupus erythematosus (SLE), detection of interferon-ß (IFNß) in B cells was found to be most prominent in patients with high anti-Smith (Sm) and renal disease, but a mechanistic connection was not clear. The objective of the present study is to determine the association of IFNß in peripheral blood naïve B cells with the histopathological features of lupus nephritis (LN). METHODS: The percentage of IFNß+ cells in IgD+CD27- naïve CD19+ B cells (B cell IFNß) among peripheral blood mononuclear cells (PBMCs) from 80 SLE patients were analyzed using flow cytometry. Serological and clinical data were collected. The correlations of B cell IFNß with LN classification and with histopathological findings (light, electron, and immunofluorescence [IF] microscopic analyses for deposition of IgM, IgG, IgA, C1q, and C3) were determined in 23 available biopsy specimens. RESULTS: B cell IFNß is positively associated with anti-Sm (p = 0.001), anti-DNA (p = 0.013), and LN (p < 0.001) but was negatively associated with oral/nasal ulcer (p = 0.003) and photosensitivity (p = 0.045). B cell IFNß positively correlated with immune complex (IC) deposit in the glomerular basement membrane (GBM) (p = 0.002) but not in the mesangial (p = 0.107) or tubular region (p = 0.313). Patients with high B cell IFNß had statistically increased development of the proliferative LN (Classes III, IV and/or V), compared to patients with low B cell IFNß (p < 0.0001). Histopathological features positively associated with increased B cell IFNß included active glomerular lesions as determined by fibrocellular crescents (p = 0.023), chronic glomerular lesions indicated by segmental sclerosis (p = 0.033), and a membranous pattern of renal damage indicated by spike/holes (p = 0.015). CONCLUSION: B cell IFNß correlates with history of severe LN, glomerular basement membrane (GBM) IC deposition, and anatomical features of both active and chronic glomerular lesions.

Abnormal time-zero histology is predictive of kidney transplant outcomes.

INTRODUCTION: Time-zero biopsies can detect donor-derived lesions at the time of kidney transplantation, but their utility in predicting long-term outcomes is unclear under the updated Kidney Allocation System. METHODS: We conducted a single-center retrospective cohort study of 272 consecutive post-reperfusion time-zero biopsies. We tested the hypothesis that abnormal time-zero histology is a strong indicator of donor quality that increases the precision of the kidney donor profile index (KDPI) score to predict long-term outcomes. RESULTS: We detected abnormal biopsies in 42% of the cohort, which were independently associated with a 1.2-fold increased hazard for a composite of acute rejection, allograft failure, and death after adjusting for clinical characteristics including KDPI. By Kaplan-Meier analysis, the relationship between abnormal time-zero histology and the composite endpoint was only significant in the subgroup of deceased donor kidney transplants with KDPI scores >35. Abnormal time-zero histology, particularly vascular intimal fibrosis and arteriolar hyalinosis scores, was independently associated with lower 12-month estimated GFR. CONCLUSION: In conclusion, abnormal time-zero histology is relatively common and identifies a group of kidney recipients at increased risk for worse long-term outcomes. Further studies are needed to determine the optimal patient population in which to deploy time-zero biopsies as an additional surveillance tool.

Open Abdominal Aortic Aneurysm Surgery and Renal Dysfunction; Association of Demographic and Clinical Variables with Proximal Clamp Location.

BACKGROUND: While cross-clamp site is a known risk factor for postoperative acute and chronic renal dysfunction following open abdominal aortic aneurysm surgery (AAA), the additive impact of patient demographic and clinical factors is lacking. In this study, we investigated the impact of body mass index (BMI), surgical duration and aneurysm diameter on the association between proximal cross-clamp location and postoperative renal dysfunction. METHODS: In this study, we conducted a retrospective analysis of 4,197 patients undergoing open AAA surgery between 2011 and 2018 using data housed in the American College of Surgeons National Safety Quality Improvement Program (ACS-NSQIP) database. The primary outcome was renal dysfunction, which was defined as patients requiring dialysis within 30 days or patients with ≥2 mg/dL rise in creatinine from baseline. We assessed the incidence of renal dysfunction with regard to clamp location and subsequently used multivariable logistic regression to assess clinical and demographic factors associated with renal dysfunction. We used a regression model to plot the association of BMI, surgical duration, and aneurysm diameter with an adjusted probability of postoperative acute and chronic renal dysfunction for individual cross-clamp locations. RESULTS: Of the 4,197 patients analyzed, 405 patients (9.6%) developed renal dysfunction within 30 days with 287 patients requiring dialysis. Patients with supraceliac clamp location had the highest incidence of renal dysfunction (20.4%). Our data showed a significant association of renal dysfunction with higher BMI patients [OR 1.04 (1.02, 1.07), P = 0.001], longer operative times [OR1.01 (1.01, 1.02), P < 0.001], clamp location between the superior mesenteric artery (SMA) and renal artery [OR 1.80 (1.17, 2.78), P = 0.007] and supraceliac clamp location [OR 2.47 (1.62, 3.76), P < 0.001]. CONCLUSIONS: The incidence of renal dysfunction increases with suprarenal clamps. Patients with higher BMI, longer operative times, and increasing aneurysm diameter, and a suprarenal clamp have a significantly increased risk of renal dysfunction compared to those who also had a suprarenal clamp but lower BMI, shorter operative times and smaller aneurysm diameter.

Three-Dimensional Transesophageal Echocardiography Simulator: New Learning Tool for Advanced Imaging Techniques.

The use of intraoperative three-dimensional (3D) transesophageal echocardiography (TEE) has grown exponentially in recent years. Three-dimensional TEE technology has evolved to allow for real-time display of 3D images and, thus, has become the standard of care for the evaluation of cardiac anatomy and function. Its use has provided a new dimension of clinical insight when managing patients for cardiac surgery or structural heart interventions. While the intraoperative utility of 3D TEE has expanded, there has been a slower advancement in the area of training and, specifically, simulator-based training in 3D TEE. This training is essential, as the skill set involved in acquiring 3D data sets differs from that of two-dimensional (2D) TEE and requires users to be able to appreciate how 3D anatomic display differs from that of tomographic cross-sectional 2D imaging. This added skill set requires mental reconstruction and spatial reorientation to appreciate the added elevational dimension in frustum-based imaging and is best achieved in a simulation environment rather than the busy operating room. In this review article, the authors evaluate the functionality of a 3D TEE simulator and how simulators such as this can establish preclinical proficiency in novices in the expanding area of advanced 3D TEE imaging.

Regional Anaesthesia for Lower Extremity Amputation is Associated with Reduced Post-operative Complications Compared with General Anaesthesia.

OBJECTIVE: Primary and secondary lower extremity amputation, performed for patients with lower extremity arterial disease, is associated with increased post-operative morbidity. The aim of the study was to assess the impact of regional anaesthesia vs. general anaesthesia on post-operative pulmonary complications. METHODS: A retrospective analysis of 45 492 patients undergoing lower extremity amputation between 2005 and 2018 was conducted using data from the American College of Surgeons National Safety Quality Improvement Program database. Multivariable logistic regression was carried out to assess differences in primary outcome of post-operative pulmonary complications (pneumonia or respiratory failure requiring re-intubation) within 48 hours and 30 days after surgery between patients receiving regional (RA) or general anaesthesia (GA). Secondary outcomes included post-operative blood transfusion, septic shock, re-operation, and post-operative death within 30 days. RESULTS: Of 45 492 patients, 40 026 (88.0%) received GA and 5 466 (12.0%) RA. Patients who received GA had higher odds of developing pulmonary complications at 48 hours (2.1% vs. 1.4%; adjusted odds ratio [aOR] 1.39, 95% confidence interval [CI] 1.09 - 1.78; p = .007) and within 30 days (6.3% vs. 5.9%; aOR 1.15, 95% CI 1.09 - 1.78; p = .039). The odds of blood transfusions (aOR 1.11, 95% CI 1.02 - 1.21; p = .017), septic shock (aOR 1.29, 95% CI 1.03 - 1.60; p = .025) and re-operation (OR 1.26, 95% CI 1.03 - 1.53; p = .023) were also higher for patients who received GA vs. patients who received RA. No difference in mortality rate was observed between patients who received GA and those who received RA (5.7% vs. 7.1%; odds ratio 0.95, 95% CI 0.84 - 1.07). CONCLUSION: A statistically significant reduction in pulmonary complications was observed in patients who received RA for lower extremity amputation compared with GA.

Donor-Derived ALECT2 Amyloidosis and Recurrent Fibrillary Glomerulonephritis in a Transplant Allograft.

The occurrence of renal amyloidosis and fibrillary glomerulonephritis in the same biopsy specimen is exceptional and poses a diagnostic challenge. We describe the case of a non-Hispanic White patient with end-stage kidney disease due to fibrillary glomerulonephritis who received a second living donor kidney from a Hispanic individual. A 40-month-posttransplantation biopsy performed for an elevated serum creatinine level revealed interstitial congophilic deposits and glomerular noncongophilic fibrillary deposits, in addition to rejection. Separate laser microdissections of the glomerular and interstitial deposits followed by liquid chromatography-tandem mass spectrometry (LC MS/MS) revealed DNAJB9 peptide spectra in glomeruli and a peptide profile consistent with leukocyte chemotactic factor 2 (ALECT2) amyloidosis in the interstitium. Based on these findings, a 2-week-posttransplantation biopsy was re-reviewed and analyzed using LC MS/MS, which revealed a peptide profile consistent with ALECT2 amyloidosis in the interstitium, without peptide spectra for ALECT2 or DNAJB9 in glomeruli. The findings were consistent with donor-derived ALECT2 amyloidosis and recurrent fibrillary glomerulonephritis. At 49 months posttransplantation, allograft function was stable with minimal proteinuria. Thus, LC MS/MS was crucial to establish the accurate diagnosis of these 2 nephropathies characterized by fibrillary deposits. The indolent posttransplantation course suggests that donated kidneys with focal interstitial ALECT2 deposits may be suitable for transplantation but the deposits persist for many years.

Enhanced Post-Operative Recovery with Continuous Peripheral Nerve Block After Lower Extremity Amputation.

BACKGROUND: Despite progress in perioperative care standards, there has not been a significant risk reduction in morbidity and mortality rates of lower extremity amputations, an intermediate risk surgery performed on high risk patients. The single-shot peripheral nerve block has shown equivocal impact on postoperative course following lower extremity amputation. Hence, we assessed the potential of preemptive use of continuous catheter-based peripheral nerve block in lower extremity amputations for reduction in pulmonary complications, acute post-operative pain scores, and opioid use in post-operative period. METHODS: A retrospective review of a quality improvement project initiated in 2018 was conducted to compare outcomes amongst general anesthesia in combination with a catheter-based peripheral nerve block (catheter group) and general anesthesia alone in patients receiving lower extremity amputation. The rate of postoperative pulmonary complications was identified as a primary endpoint. The secondary outcomes assessed were acute post-operative pain scores and opioid consumption up to 48 hours. Our analysis was adjusted for potential confounding variables inclusive of demographics, medical comorbidities, type of surgical procedure and smoking status. RESULTS: Ninety-six patients were included in the study (61 in the general anesthesia group, 35 in the catheter group). After adjusting for baseline demographics, comorbidities, surgical technique and smoking status, the odds of postoperative pulmonary complications were significantly lower with catheter-based peripheral nerve block in comparison to general anesthesia alone, OR 0.11 [95% CI, 0.01- 0.88] (P = 0.048). The decrease in acute pain scores was also observed in the catheter group when compared to general anesthesia alone, OR 0.72 [95% CI, 0.56 - 0.93] (P = 0.012). Similarly, the opioid consumption was also lower in the catheter group in comparison to general anesthesia alone, OR 0.97 [95% CI, 0.95 - 0.99] (P = 0.025). CONCLUSION: Preemptive use of continuous peripheral nerve block in patients undergoing lower extremity amputation reduces the incidence of pulmonary complications, acute postoperative pain scores and narcotic use in post-operative period.

Protocolized Based Management of Cerebrospinal Fluid Drains in Thoracic Endovascular Aortic Aneurysm Repair Procedures.

BACKGROUND: Spinal cord ischemia (SCI) resulting in paraplegia is a devastating complication associated with thoracic endovascular aortic aneurysm repair (TEVAR) whose incidence has significantly declined over time. In this review, we present our experience with a multidisciplinary clinical protocol for cerebrospinal fluid (CSF) drain management in patients undergoing TEVAR. Furthermore, we aimed to characterize complications of CSF drain placement in a large, single center experience of patients who underwent TEVAR. METHODS: This retrospective review is of patients undergoing TEVAR with and without CSF drain placement between January 2014 and December 2019 at a single institution. Patient demographics, hospital course, and drain-related complications were analyzed to assess the incidence of CSF drain-related complications. RESULTS: A total of 235 patients were included in this study, of which 85 received CSF drains. Eighty patients (94.1%) were placed by anesthesiologists, while 5 (5.9%) were placed under fluoroscopic guidance by interventional neurosurgery. The most common level of placement was L3-L4 in 38 (44.7%) cases followed by L4-L5 in 36 (42.4%) cases. The mean duration of CSF drain was 1.9 ± 1.4 days. Complications due to CSF drainage occurred in 5 (5.9%) patients and included partial retainment of catheter, subdural edema, epidural hematoma, headache, and bleeding near the drain site. The overall 30-day mortality rate was 5.5% and did not differ between those who received a CSF drain and those who did not (P = 0.856). The overall incidence of SCI resulting in paraplegia was 1.7% in the studied patients. CONCLUSIONS: A protocol-based CSF drainage program for spinal cord protection involves a multifaceted approach in identification and selection of patients meeting criteria for prophylactic drain placement, direct closed loop communication, and perioperative management by an experienced team. Despite the inherent advantages of CSF drain placement, it is not without complications, thus risk and benefit need to be weighed in context of the procedure and the patient with close communication and team approach.

In vitro anti-leishmanial activity of Prunus armeniaca fractions on Leishmania tropica and molecular docking studies.

Prunus armeniaca (L.) is a member of the Rosaceae, subfamily Prunoideae, shows anticancer, antitubercular, antimutagenic, antimicrobial, antioxidant, and cardioprotective activities. Here we fractionated the leaves extract of this highly medicinally important plant for antileishmanial activity. In the current study, the leaves extract was fractionated and characterized using column and thin layer chromatography by n-hexane, ethyl acetate, and methanol solvents. Twelve fractions were isolated and subjected for evaluation of their cytotoxicity and in vitro antileishmanial activity against promastigotes and amastigotes of Leishmania tropica. Among all fractions used, the fraction (F7) exhibited the strongest antileishmanial activity. The bioactive fraction was further characterized by spectroscopy (FTIR, UV-Vis), and GC-MS analysis. The in silico docking was carried out to find the active site of PTR1. All derived fractions exhibited toxicity in the safety range IC50 > 100 µg/ml. The fraction (F7) showed significantly the highest antipromastigotes activity with IC5011.48 ± 0.82 µg/ml and antiamastigotes activity with IC50 21.03 ± 0.98 µg/ml compared with control i.e. 11.60 ± 0.70 and 22.03 ± 1.02 µg/ml respectively. The UV-Vis spectroscopic analysis revealed the presence of six absorption peaks and the FTIR spectrum revealed the presence of alkane, aldehyde, carboxylic acid, thiols, alkynes, and carbonyls compounds The GC-MS chromatogram exhibited the presence of nine compounds: (a) benzeneethanol, alpha, beta dimethyl, (b)carbazic acid, 3-(1 propylbutylidene)-, ethyl ester, (c)1, 2-benzenedicarboxylic acid, diisooctyl ester, (d)benzeneethanamine a-methyl, (e)2aminononadecane, (f)2-heptanamine-5-methyl, (g)cyclobutanol, (h)cyclopropyl carbine, and (i)nitric acid, nonyl ester. Among all compounds, the 1, 2-benzenedicarboxylic acid, diisooctyl ester bound well to the PTR1 receptor. Fraction (F7) showed acceptable results with no cytotoxicity. However, in vivo studies are required in the future.

Use of Erector Spinae Plane Block in Thoracic Surgery Leads to Rapid Recovery From Anesthesia.

BACKGROUND: Ultrasound guidance has resulted in a continuous evolution in techniques for pain control for video-assisted thoracoscopic surgery (VATS). The objective of this study was to compare erector spinae plane block with intercostal block as multimodal analgesia to elucidate quality of postoperative pain control and preservation of pulmonary function after VATS. METHODS: A consecutive cohort of patients undergoing elective VATS was enrolled in the study and divided into erector spinae plane block and intercostal block groups. Spirometry and visual analog scale pain score exams were performed to measure forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, and forced expiratory flow in intervals of 25% to 75%. Chronic pain was assessed by reviewing surgical follow-up notes. RESULTS: Seventy-eight patients were included. Comparing the erector spinae plane block group with the intercostal block group found significant improvement in visual analog scale pain score (3.2 vs 6.4, P < .001), postanesthesia care unit length of stay (127.3 vs 189.5 minutes, P = .045), preservation in lung volume parameters at 2 hours (FVC: 40.5% vs 51.4%, P < .001; FEV1: 40.9% vs 53.8%, P < .001; and forced expiratory flow in intervals of 25%-75%: 39.7% vs 53.7%, P = .019) and at 24 hours (FVC: 37.8% vs 50.5%, P < .001; FEV1: 34.3% vs 51.9%, P < .001; forced expiratory flow in intervals of 25%-75%: 27.1% vs 56.3%, P < .001), respectively. CONCLUSIONS: Erector spinae plane block improves acute and chronic pain control and preserves lung function. Thus, it has the potential for enhanced recovery from VATS as part of a multimodal analgesia regimen.

Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study.

Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, ß2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.

Glomerular Immunodeposits of Patients with IgA Nephropathy Are Enriched for IgG Autoantibodies Specific for Galactose-Deficient IgA1.

BACKGROUND: IgA nephropathy (IgAN) is the leading primary GN worldwide. The disease is thought to result from glomerular deposition of circulating immune complexes of IgG bound to galactose-deficient IgA1 (Gd-IgA1). However, routine immunofluorescence microscopy fails to detect IgG in many kidney biopsies from patients with IgAN and the specificity of IgG in immunodeposits has not been tested. METHODS: We used remnant frozen kidney-biopsy specimens from 34 patients with IgAN; 14 were IgG-positive and 20 were IgG-negative by routine immunofluorescence microscopy. Six patients with primary membranous nephropathy (MN) and eight with lupus nephritis (LN) served as controls. IgG in the kidney tissue was extracted and its amount determined by ELISA. IgG molecular integrity was assessed by SDS-PAGE immunoblotting. Antigenic specificity of extracted IgG was determined by ELISA using phospholipase A2 receptor (PLA2R) or Gd-IgA1 as antigen. In addition, ten other IgAN cases, six IgG-positive and four IgG-negative by routine immunofluorescence, were used for colocalization studies by confocal microscopy. RESULTS: IgG extracted from MN but not IgAN immunodeposits reacted with PLA2R. Conversely, IgG extracted from IgAN but not MN or LN immunodeposits reacted with Gd-IgA1. Even IgAN kidney-biopsy specimens without IgG by routine immunofluorescence microscopy had IgG specific for Gd-IgA1. Confocal microscopy confirmed the presence of IgG in the IgAN biopsies with colocalization of glomerular IgA and IgG. CONCLUSIONS: These results reveal for the first time that IgAN kidney biopsies, with or without IgG by routine immunofluorescence, contain Gd-IgA1-specific IgG autoantibodies. These findings support the importance of these autoantibodies in the pathogenesis of IgAN.

Technical Varieties of Ross Procedure: A Case Series.

Replacement of aortic valve with the pulmonary autograft is carried out through the Ross procedure due to its potential for growth, durability in pediatric population, and absence of anticoagulation. This case series reports the postoperative outcome of two technical variations of Ross procedure in eight patients who underwent surgery from January 2007 to December 2016. The dominant valvular hemodynamic indication was aortic regurgitation. The techniques employed for Ross procedure included free standing root replacement in six patients and modified root replacement with autograft stabilisation using Dacron interposition graft in two patients. Right ventricular outflow tract (RVOT) conduit reconstruction was achieved by utilisation of Contegra bio prosthesis in four patients; and use of manually constructed valved conduit comprising of PTFE (polytetrafluoroethelene) membrane and bovine pericardial tube in remaining four patients. There was no mortality and no re-intervention. The technical varieties of Ross procedure offer freedom from need of anti-coagulation, mortality, and RVOT conduit failure in younger adults.

Rare Presentation of a Posterior Mediastinal Cystic Schwannoma as a Large Pleural Effusion.

A 46-year-old man presented with shortness of breath and recurrent, left-sided pleural effusions. A computed tomography (CT) scan of the chest showed a large, left-sided pleural effusion with a mass in the posterior mediastinum. A pleural tap showed lymphocytic exudate. The biopsy of the mass was inconclusive. A left posterolateral thoracotomy was performed, which showed a large posterior mediastinal mass adherent to the left lung. The mass was completely excised and the histopathology proved it to be giant predominantly cystic schwannoma. The pleural effusion resolved after tumor resection.

Haploinsufficiency of the Transcription Factor Ets-1 Is Renoprotective in Dahl Salt-Sensitive Rats.

Studies using Dahl salt-sensitive (SS) rats identified specific quantitative trait loci that predispose animals to hypertension-associated albuminuria and kidney injury. We explored the hypothesis that kidney-specific expression of the transcription factor Ets-1, located within one of these loci on chromosome 8, mediates glomerular injury in SS hypertension. During the first week on a high-salt diet, SS rats and SS rats with only one functioning Ets-1 gene (ES rats) demonstrated similar increases in BP. However, serum creatinine concentration, albuminuria, and glomerular expression of ETS-1 and two ETS-1 targets, MCP-1 and MMP2, did not increase as substantially in ES rats as in SS rats. Mean BP subsequently increased further in SS rats and remained higher than that of ES rats for the rest of the study. After 4 weeks of high-salt intake, ES rats still showed a lower mean serum creatinine concentration and less albuminuria, as well as less histologic evidence of glomerular injury and kidney fibrosis, than SS rats did. To investigate the specific contribution of renal Ets-1, we transplanted kidneys from ES or SS rats into salt-resistant SS-Chr 13BN/McwiCrl (SS-13BN) rats. Within 10 days on a high-salt diet, BP increased similarly in ES and SS allograft recipients, becoming significantly higher than the BP of control isograft recipients. However, mean serum creatinine concentration and albuminuria remained lower in ES allograft recipients than in SS allograft recipients at 2 weeks, and ES allografts showed less glomerular injury and interstitial fibrosis. In conclusion, reduced renal expression of ETS-1 prevented hypertension-associated kidney injury in SS rats.