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Objective: The aim of this study was to evaluate the patency of bridging covered stents (BCS) bridged to inner branches in custom-made thoracoabdominal endografts., Methods: This was a single-center retrospective study identifying all patients undergoing fenestrated or branched endovascular aortic repair (f/b EVAR) in whom the reno-visceral target vessels (TVs) were bridged with a BCS to an inner branch of a custom-made (CMD) endograft. Technical success and perioperative complications were noted. Follow-up BCS patencies were evaluated, and in patients with follow-up, two groups based on BCS were created, a group with BCS occlusion and a group with BCS patent. Univariable and multivariable analyses were performed to analyze factors related to visceral and renal bridging stent occlusion., Results: From 2019 through 2022, 69 patients undergoing complex aortic repair had at least one TV bridged to an inner branch built into a CMD endograft. Eighty-six percent of the grafts had only inner branches, whereas 14% had a mix of fenestrations for the visceral TVs and inner branches for the renal arteries. Twenty-five percent of patients presented as urgent and received an endograft originally designed for another patient and available on our shelf at the time. A total of 245 TVs were connected to inner branches: celiac trunk (CT), 54; superior mesenteric artery (SMA), 59; and renal artery (RA), 132. Technical success was 99%. There was a 23% complication and 9% perioperative mortality rate. At follow-up, we identified 6% of visceral and 14% of renal BCS occlusions. The primary patency for RA BCS was 83% at 12 months and 58% at 24 months. For the CT-SMA BCS, Kaplan-Maier showed a patency of 99% and 96% at 12 and 24 months. In the univariate analysis, a misaligned TV ostium (P = .001), the postoperative BCS diameter on postoperative computed tomography angiography (P = .02), and the preoperative infrarenal aortic angle >60° (P = .007) were correlated with RA BCS occlusion. In the multivariate analysis, only the misaligned TV ostium (P = .002) and infrarenal angle >60° (P = .01) were significantly correlated., Conclusions: In our series of complex aortic repair, the incorporation of inner branches to bridge TVs is associated with a high renal BCS occlusion rate. Improper alignment of the branches with the TV ostium and acute aortic angles might play a significant role. Further research on this technology is needed., Competing Interests: Disclosures T.K. has intellectual property with Cook Medical., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Iliac branch devices (IBDs) have shown good results but there is little evidence for the risk of internal iliac artery (IIA) endoleak, so there are no clear recommendations on the maximum diameter it should be. Based on limited evidence, it was hypothesised that an IIA of ≥ 11 mm in diameter presents an increased risk of type Ic endoleak., Methods: This was a single centre, retrospective case control study. Patients undergoing an IBD with the main trunk of the IIA as the target vessel, between 2015 and 2021, were identified. Two groups were created: those with a main trunk diameter of < 11 mm; and those with a diameter of ≥ 11 mm. Technical success, freedom from type Ic endoleak, and re-intervention rates were compared. A receiver operating characteristic (ROC) curve was performed to show a cutoff IIA diameter value for risk of type Ic endoleak. Multivariate analysis was performed to assess the risk of type Ic endoleak and the presence of calcification, stenosis, and landing zone length in the IIA., Results: There were 182 IBDs identified. The dilated IIA group (54 IBDs) had significantly lower technical success (91% vs. 98.4%; p = .002), lower freedom from type Ic endoleak (77% vs. 97.1% at 24 months; p = .001), and lower freedom from re-interventions (70% vs. 92.4% at 24 months; p = .002). The ROC curve showed that 10.5 mm was the cutoff diameter for type Ic endoleak. Moderate or severe calcification as well as landing zone length < 5 mm also correlated with type Ic endoleak., Conclusion: IBDs have a statistically significantly higher rate of technical failure, lower freedom from type Ic endoleak, and lower freedom from re-intervention when the IIA is ≥ 11 mm in diameter., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Fenestrated and branched endovascular aortic repair (F/BEVAR) of thoracoabdominal aortic aneurysms (TAAAs) has shown high technical success and low early mortality rates. Aneurysm extent has been reported as a factor affecting outcomes. This study aimed to assess the early and midterm follow-up outcomes of patients managed by F/BEVAR for types I through III TAAAs., Methods: A single-center retrospective analysis was conducted, including data from consecutive, elective and urgent (symptomatic and ruptured cases), patients treated for types I through III TAAAs, between October 1, 2011, and October 1, 2022, using F/BEVAR. Degenerative and postdissection TAAAs were included. Patients received prophylactic cerebrospinal fluid drainage (CSFD), except those under therapeutic anticoagulation, those who were hemodynamically unstable, or those with failed CSFD application. When an initial thoracic endovascular aortic repair was performed, as part of a staged procedure, no CSFD was used. Later stages and nonstaged procedures were performed under CSFD. Thirty-day mortality and major adverse events (MAEs) were analyzed. Kaplan-Meier estimates were used for follow-up outcomes., Results: F/BEVAR for types I through III TAAAs was performed in 209 patients (56.9% males; mean age, 69.6 ± 3.2 years; mean aneurysm diameter, 65.2 ± 6.2 mm); 29.2% type I, 57.9% type II, and 12.9% type III. Urgent repair was performed in 26.7% of patients (56 cases; 23 ruptured and 33 symptomatic cases) and 153 were treated electively. Thirty-two patients (15.3%) were classified as American Society of Anesthesiologists (ASA) class IV. CSFD was used in 91% and staged thoracic endovascular aortic repair was performed in 51.2% of patients. Technical success was 93.8% (96.7% in elective vs 94.6% in urgent cases; P = .92). Thirty-day mortality was 11.0% (4.6% in elective vs 28.5% in urgent cases; P < .001) and MAEs were recorded in 17.2% of cases (7.8% in elective vs 42.8% in urgent cases; P < .001). Spinal cord ischemia rate was 20.5% (17.6% in elective vs 28.7% in urgent cases; P = .08), whereas 2.9% of patients presented paraplegia (1.3% in elective and 7.1% in urgent cases; P = .03). The mean follow-up was 16 ± 5 months. Survival was 75.0% (standard error, 4.0%) and freedom from reintervention was 73.3% (standard error, 4.4%) at 36 months. ASA IV and urgent repair were detected as independent factors related to early mortality and MAE, whereas ruptured aneurysm status was related to spinal cord ischemia evolution., Conclusions: Endovascular repair for types I through III TAAAs provides encouraging early outcomes in terms of mortality, MAE, and paraplegia, especially in an elective setting. Setting of repair and baseline ASA score should be taken into consideration during decision-making., Competing Interests: Disclosures N.T. is a proctor for Cook Medical and has intellectual property with Cook Medical and Bentley receiving institutional fees. T.K. is a consultant and proctor for and has intellectual property with Cook Medical, receiving royalties, speaking fees, and research, travel, and educational grants. The remaining authors report no conflicts., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Infective native aortic aneurysms (INAAs), formerly called mycotic aneurysms, remain an uncommon disease with significant heterogeneity among cases; hence, there is lack of solid evidence to opt for the best treatment strategy. The present study aims to describe a 20-year experience at a single institution treating this uncommon condition., Methods: Retrospective study of all patients treated for INAA at a single academic hospital in Santiago, Chile, between 2002 and 2022. Clinical characteristics are described, as well as operative outcomes per type of treatment. Nonparametric Mann-Whitney U-test or Kruskal-Wallis tests were performed when appropriate, and results were reported as median and ranges. Survival at given timeframes was determined by a Kaplan-Meier curve, with analysis performed through a Cox regression model., Results: During the study period, 1,798 patients underwent aortic procedures at our center, of which 35 (1.9%) were treated for INAA. Of them, 25 (71.4%) were male. One patient had 2 INAAs. Median age was 69.5 years (range: 34-89 years). Of the 36 INAAs, the most frequent location was the abdominal and thoracic aorta in 20 (55.5%) and 11 (30.5%) cases, respectively, followed by the iliac arteries in 4 (11.1%) cases. One (2.7%) patient presented a thoracoabdominal INAA. Overall, endovascular treatment associated with long-term antibiotics was used in 20 (57.1%) patients: 4 of them underwent hybrid treatment. Fifteen (42.8%) patients underwent direct aortic debridement followed by in situ or extra anatomic revascularization. There was a significant difference in age between both treatment strategies (a median of 76.5 years for endovascular versus a median of 57 years for open, P = 0.011). The median hospital stay was 15 days (range: 2-70 days). The early complications rate (<30 postoperative days) was 20% (n = 7). Early mortality rate (inhospital or before postoperative 30 days) was 14.2% (n = 5). Median follow-up was 33 months (range: 6-216 months). The overall survival rates at 1, 3, and 5 years were 69.9% (standard error [SE] 8.0), 61.7% (SE 9.8), and 50.9% (SE 11.8), respectively. Five-year survival rate of patients undergoing endovascular treatment compared with open approach was 45.9% (SE 15.1) versus 80.0% (SE 17.8), respectively (P = 0.431). There were no significant differences in survival between open and endovascular treatment, hazard ratio 3.58 (confidence interval 95%: 0.185-1.968, SE ± 0.45 P = 0.454)., Conclusions: Patients treated by endovascular approach were older than patients treated by open approach. Even though, the open group had a higher 5-year survival rate than the endovascular group, not statically significance differences were found between treatments., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to evaluate renal function and renal parenchymal length changes secondary to the coverage or preservation of accessory renal arteries (ARAs) in complex aortic repair., Methods: This was a single-center retrospective study identifying all patients undergoing fenestrated or branched endovascular aortic repair (f-b EVAR) who presented with ARAs. Two groups were created, a preserved ARA group, with incorporation of the vessel as a dedicated fenestration or branch in the endograft plan, and a non-preserved ARA group, without incorporation of them. Early >30% decline of glomerular filtration rate (GFR), kidney infarcts, and endoleaks were evaluated. Mid-term results with freedom from kidney shrinkage (defined as length decrease >10%) at follow-up, freedom from GFR decrease >30%, or need for postoperative dialysis at follow-up were also analyzed. Primary assisted patency of incorporated ARAs was calculated., Results: From 2011 through 2020, 145 patients undergoing complex aortic repair presented with an ARA. After excluding ruptured aneurysms, 33 patients had the ARA preserved with their incorporation into the stent graft (preserved ARA group), and 99 did not have preservation of them (not-preserved ARA group). There were no statistical differences in demographics or type of aneurysm. Patients in the ARA-preserved group had more ARAs (median of two per patient vs one in the non-preserved ARA group; P = .01) and bigger ARAs (median 4 vs 3 mm in the non-preserved ARA group; P = .001). Early postoperative worsening >30% of GFR (23% vs 6%; P = .03) as well as postoperative renal infarction (57% vs 6%; P = .001) and ARA-related endoleaks (20% vs 0%; P = .01) were statistically higher for the not-preserved ARA group. Mid-term kidney length showed significant shrinkage in the not-preserved ARA group compared with the ARA preserved group (9.7% vs 0%; P = .001). Freedom from >30% GFR decline at 2 years was significantly higher for the preserved ARA group (83% vs 47%; P = .01).Two-year primary assisted patency of incorporated ARA was 94%., Conclusions: Complex aortic repair incorporation of ARA is feasible, with low complications and good primary assisted patency at 2 years. It leads to less postoperative early renal dysfunction as well as higher freedom for mid-term renal disfunction and kidney shrinkage., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Frozen section is a standard of care procedure during thoracic surgery when an immediate diagnosis is needed. An alternative procedure is intraoperative cytology. Video-assisted thoracic surgery is currently widely used for thoracic surgical procedures. The aim of this study was to assess intraoperative cytology together with frozen section for accuracy, turnaround time, and total response time during video-assisted thoracic surgery., Methods: We included patients having video-assisted thoracic surgery between August 2018 and February 2019 at our institution. A cytopathologist and a surgical pathologist independently performed intraoperative cytology and frozen sections, respectively. Final histologic diagnosis was the reference standard. Intraoperative cytology, frozen section turnaround, and total response times were analyzed., Results: A total of 52 specimens from 27 patients were included. The intraoperative cytology correlated with final histology in 98% of cases. Frozen section correlated with final histology in 100% of cases. Intraoperative cytology turnaround and total response times were equal (mean, 4.35 minutes; range, 2-15 minutes). Mean frozen section turnaround and response times were 26.2 minutes (range, 9-61 minutes) and 36.7 minutes (range, 16-90 minutes), respectively. We found a statistically significant difference between intraoperative cytology and frozen section turnaround time and total response times (P < .001)., Conclusions: This study highlights that intraoperative cytology could be as accurate as frozen section and considerably faster during video-assisted thoracic surgery (P < .001). Total response time could potentially be used as a quality metric for video-assisted thoracic surgery., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Acute exacerbations of fibrosing interstitial lung disease (ILD) occur in both idiopathic pulmonary fibrosis (IPF) as well as non-IPF ILDs. An expert consensus definition has allowed for more frequent reporting of IPF exacerbations. The same is lacking for non-IPF ILD exacerbations. The incidence of non-IPF ILD exacerbations is likely less than in IPF, but the two entities share similar risk factors, such as increased frequency as physiologic derangements advance. The radiologic and histopathologic spectrum of acute ILD exacerbations extends from organizing pneumonia (OP) to the more treatment-refractory diffuse alveolar damage (DAD) pattern. Indeed, responsiveness to various therapies may depend on the relative components of these entities, favoring OP over DAD. There are no proven therapies for acute ILD exacerbations. Corticosteroids are a mainstay in any regimen although clear evidence of benefit does not exist. A variety of immunosuppressant agents have purported success in historical cohort studies - cyclophosphamide, cyclosporine A, and tacrolimus most commonly. Only one randomized controlled trial has been published, studying recombinant thrombomodulin for IPF exacerbation, but the primary outcome of survivor proportion at 90 days was not met. Other novel therapies for ILD exacerbations are still under investigation. The short and long-term prognosis of acute exacerbations of ILD is poor, especially in patients with IPF. Transplant referral should be considered early for both IPF as well as fibrosing non-IPF ILDs, given the unpredictability of the exacerbation event., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Delayed graft function (DGF) in renal transplant is associated with reduced graft survival and increased immunogenicity. The complement-driven inflammatory response after brain death (BD) and posttransplant reperfusion injury play significant roles in the pathogenesis of DGF. In a nonhuman primate model, we tested complement-blockade in BD donors to prevent DGF and improve graft survival. BD donors were maintained for 20 hours; kidneys were procured and stored at 4°C for 43-48 hours prior to implantation into ABO-compatible, nonsensitized, MHC-mismatched recipients. Animals were divided into 3 donor-treatment groups: G1 - vehicle, G2 - rhC1INH+heparin, and G3 - heparin. G2 donors showed significant reduction in classical complement pathway activation and decreased levels of tumor necrosis factor α and monocyte chemoattractant protein 1. DGF was diagnosed in 4/6 (67%) G1 recipients, 3/3 (100%) G3 recipients, and 0/6 (0%) G2 recipients (P = .008). In addition, G2 recipients showed superior renal function, reduced sC5b-9, and reduced urinary neutrophil gelatinase-associated lipocalin in the first week posttransplant. We observed no differences in incidence or severity of graft rejection between groups. Collectively, the data indicate that donor-management targeting complement activation prevents the development of DGF. Our results suggest a pivotal role for complement activation in BD-induced renal injury and postulate complement blockade as a promising strategy for the prevention of DGF after transplantation., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Few series of ruptured abdominal aortic aneurysm (RAAA) from Latin America have been published., Objectives: To report the outcomes of RAAA treated with open surgical repair (OSR) in a University Hospital in Chile. Secondary objectives are the identification of prognostic factors and survival rates., Methods: Retrospective review of consecutive RAAA patients treated with OSR between September 1979 and December 2017. Medical records, diagnostic images, and follow-up details were obtained. Statistical methods include multiple logistic regression analysis., Results: One hundred and sixteen patients underwent OSR for RAAA. The average age was 72.3 years (54-95), 62.9% ≥ 70 years, and 81.9% male. Preoperative systolic pressure <90 mm Hg was present in 74 patients (63.8%), and 10 (8.6%) experienced cardiac arrest before surgery. Only 30.2% were known to have an AAA before rupture. The mean aortic diameter was 7.9 cm. Sixteen patients had juxtarenal aneurysms (13.8%). The rupture was intra or retroperitoneal in 111 cases (95.7%), there were 4 fistulas to neighboring veins and one into the duodenum. Reconstruction included tubular graft in 39.7% and bifurcated in 58.6%. The estimated mean blood loss was 3,456 ± 2,768 mL (median 3,000). Mean mechanical ventilation was 7.4 ± 12.0 days and hemodialysis requirement in 21.8%. Six patients died during surgery and other 24 during the first postoperative month or in hospital, for an overall mortality rate of 25.9%. Age ≥70 years (P < 0.01), blood pressure less than 90 mm Hg (P = 0.03) and dialysis (P < 0.01) were associated with higher 30-day mortality rates. The survival rate was 68.0, 65.3, 44.3, and 25.2% at 1, 2, 5, and 10 years, respectively., Conclusions: EVAR for RAAA is not affordable in every country. Outcomes of open RAAA repair at our institution are similar to results reported recently for OSR by the USA and European Medical centers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In non-small cell lung cancer (NSCLC), 18 fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) assists in diagnosis, staging, and evaluating treatment response. One variable of FDG-PET, the maximum standard uptake value (SUV m ), is considered an objective measure of glucose uptake. However, little is known about the fate of glucose in FDG-avid lung tumors in vivo. This study used stable glucose isotope tracing to determine whether the SUV m predicts glycolytic metabolism or other glucose fates in tumors., Methods: In this prospective Institutional Review Board-approved clinical trial, 52 untreated potentially resectable confirmed NSCLC patients underwent FDG-PET computed tomography. During the surgical procedure, the patients were infused with 13 C-labeled glucose. Blood, tumor, and normal lung samples were analyzed by mass spectrometry to determine 13 C enrichment in glycolytic intermediates. These values were compared with clinical variables, including SUV m , maximum tumor diameter, stage, grade, and MIB-1/Ki67 proliferation index., Results: For each patient, 13 C enrichment in each metabolite was compared between tumor and adjacent lung. Although all tumors metabolized glucose, SUV m did not correlate with glycolytic intermediate labeling. Rather, SUV m correlated with markers indicating the use of other respiratory substrates, including lactate, and with the proliferation index., Conclusions: SUV m does not correlate with glycolytic metabolism in human NSCLC but does correlate with the proliferation index, suggesting that SUV m predicts glucose use by pathways other than glycolysis. These pathways may offer alternative therapeutic targets, including biosynthetic pathways required for cell proliferation. The research techniques in this study offer the opportunity to understand the relationships between SUV m , tumor metabolism, and therapeutic vulnerabilities in human NSCLCs., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Pathologic antibody-mediated rejection (pAMR) occurs in 10% of cardiac transplant patients and is associated with increased mortality. The endomyocardial biopsy remains the primary diagnostic tool to detect and define pAMR. However, certain challenges arise for the pathologist. Accurate identification of >10% of intravascular macrophages along with endothelial swelling, which remains a critical component of diagnosing pAMR, is one such challenge. We used double labeling with an endothelial and histiocytic marker to improve diagnostic accuracy. Twenty-two cardiac transplant endomyocardial biopsies were screened using a CD68/CD31 immunohistochemical (IHC) double stain. To determine whether pAMR diagnosis would change using the double stain, intravascular macrophage staining was compared to using CD68 alone. Twenty-two cardiac pAMR cases from patients were included. Fifty-nine percent of cases previously called >10% intravascular macrophage positive by CD68 alone were called <10% positive using the CD68/CD31 double stain. Not using the double stain was associated with a significant overcall. In C4d-negative cases, using the CD68/CD31 double stain downgraded the diagnosis of pAMR2 to pAMR1 in 32% of cases. It was concluded that more than one third of patients were overdiagnosed with pAMR using CD68 by IHC alone. We demonstrate the value of using a CD68/CD31 double stain to increase accuracy., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Although we know that young patients with peripheral artery disease (PAD) have worse outcomes than older patients, there is a scarcity of information about the incidence of hypercoagulability in this population. Our aim was to analyze outcomes of young patients diagnosed with a hypercoagulable state (unusual tendency toward thrombosis) after lower extremity revascularization compared with similar patients without hypercoagulability., Methods: All patients 50 years of age or younger undergoing an initial procedure for lower extremity PAD from 2000 to 2015 at the Cleveland Clinic were retrospectively analyzed. Patients with a hypercoagulability panel were included and classified into groups as hypercoagulable positive (HP) or hypercoagulable negative (HN). Demographics, preoperative risk factors, form of presentation, level of disease, and type of intervention were analyzed in addition to perioperative complications, early failure, and length of stay. Primary outcomes were limb loss and primary, primary assisted, and secondary patencies. Outcomes were analyzed and Kaplan-Meier curves generated., Results: Ninety-one patients were included for a total of 118 limbs. Mean follow-up was 32 months; 55% of patients had a hypercoagulable disorder, with 59% having lupus anticoagulant and 32% hyperhomocysteinemia. In the HP group, 71% were men; 49% were men in the HN group. Patients overall had a high prevalence of smoking (86%), hypertension (36%), and hyperlipidemia (33%). Acute limb ischemia was the most common form of presentation for both groups (50% HP, 38% HN). The aortoiliac segment was the most commonly affected (38% HP, 50% HN). The most frequent operation in the HN group was endarterectomy or bypass (32%); in the HP group, it was an endovascular intervention (29%). Perioperative occlusion or failure was 18% in the HN group vs 30% in the HP group (P > .05). Primary patency, primary assisted patency, and secondary patency at 36 months were all better for the HN group (no statistical significance) in all treatment groups. Major amputation at 36 months was significantly worse for the HP group (40% vs 10% in the HN group; P < .005). There was no difference in perioperative complications or length of stay., Conclusions: Young patients undergoing lower extremity revascularization for PAD have worse outcomes when associated with hypercoagulability. There are trends to decreased patency of revascularization in these patients, with significantly more major amputations. No clear differences between modalities of treatment were demonstrated., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Patients with hypersensitivity pneumonitis are at risk of developing pulmonary fibrosis, which is associated with reduced survival. In families with multiple affected members, individuals might be diagnosed as having idiopathic pulmonary fibrosis (IPF) or chronic (fibrotic) hypersensitivity pneumonitis, which suggests these disorders share risk factors. We aimed to test whether the genomic risk factors associated with the development and progression of IPF are also associated with the development of fibrosis and reduced survival in people with chronic hypersensitivity pneumonitis., Methods: We did an observational study of two independent cohorts of patients with chronic hypersensitivity pneumonitis, one from the University of California San Francisco, CA, USA (UCSF), and one from the University of Texas Southwestern, TX, USA (UTSW). We measured two common single-nucleotide polymorphisms associated with IPF (MUC5B rs35705950 and TOLLIP rs5743890) and telomere length in peripheral blood leucocytes, and assessed their associations with chronic hypersensitivity pneumonitis risk, survival, and clinical, radiographic, and pathological features. We compared findings with those in patients with IPF from the UCSF and UTSW cohorts, and healthy controls from the European population of the 1000 Genomes Project Phase 3, version 1., Findings: The cohorts included 145 patients from UCSF and 72 from UTSW. The minor allele frequency (MAF) was greater for MUC5B rs35705950 in patients with chronic hypersensitivity pneumonitis than in healthy controls (24·4% in UCSF and 32·3% in UTSW vs 10·7%, both p<0·0001), but not for TOLLIP rs5743890. The MAFs were similar to those for IPF (UCSF 33·3%, p=0·09; UTSW 32·0%, p=0·95). In the combined UCSF and UTSW chronic hypersensitivity pneumonitis cohort, we saw associations between extent of radiographic fibrosis and MUC5B rs35705950 minor alleles (adjusted odds ratio [OR] 1·91, 95% CI 1·02-3·59, p=0·045) and short telomere length (adjusted OR per unit change in mean natural logarithm-transformed ratio of telomere repeat copy number to single gene copy number 0·23, 0·09-0·59, p=0·002). Telomere length less than the tenth percentile for age was also significantly associated with reduced survival (log-rank p=0·006)., Interpretation: The associations between MUC5B rs35705950 and short telomere length with extent of fibrosis, histopathological features of usual interstitial pneumonia, and reduced survival in patients with chronic hypersensitivity pneumonitis suggest shared pathobiology with IPF, and might help to stratify risk., Funding: National Institutes of Health and Nina Ireland Program for Lung Health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The carotid bifurcation can host a variety of tumors requiring complex surgical management. Treatment requires resection and, in some cases, vascular reconstruction that may compromise the cerebral circulation. The most frequent lesion at this location is the carotid body tumor (CBT). CBT are classified according to Shamblin in 3 types depending on the degree of carotid vessels encasement. Our main objective was to report our clinical experience managing carotid bifurcation tumors throughout the last 30 years., Methods: Between 1984 and 2014, we treated 30 patients with 32 carotid bifurcation tumors. There were 21 women and 9 men (2.3:1), with a mean age of 45.5 years (18-75). The most frequent presentation was an asymptomatic neck swelling or palpable mass localized at the carotid triangle (86.7%)., Results: Thirty of 32 tumors were resected. Since 1994, computed tomography scan has been the most frequently used diagnostic imaging tool (80%), followed by magnetic resonance imaging. Angiography was used mainly during the first 10 years of the study period. Mean size of the tumor was 44.6 mm (20-73 mm). Nineteen (63%) were classified as Shamblin II and 6 (20%) as Shamblin's III. All specimens were analyzed by a pathologist; 28 tumors (93%) were confirmed as paragangliomas, 2 (7%) were diagnosed as schwannomas. Two patients underwent preoperative embolization of the CBT; 5 patients (17%) required simultaneous carotid revascularization, all of them Shamblin III. Mean hospitalization time was 4.5 days (1-35 days). Transient extracranial nerve deficit was observed in 7 patients (23.3%). Three patients (Shamblin III) required red blood cells transfusion. One patient (Shamblin III) underwent a planned en bloc excision of the vagus nerve. There was no perioperative mortality or procedure-related stroke. No malignancy or tumor recurrence were observed during follow-up., Conclusions: CBTs can be diagnosed on clinical grounds requiring vascular imaging confirmation. These infrequent lesions are generally benign. Early surgical removal by surgeons with vascular expertise avoids permanent neurologic and or vascular complications., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor-specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean-calculated panel-reactive antibody and MFImax ranged from 10.3-57.2% and 262-1691, respectively, between low- and high-risk protocols. Mean MFImax increased significantly from transplant to 1 week and 1 year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71-6.45) and increased specific antibodies at 1-week post transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients.

Morphological changes that occur during kidney injury involve actin skeleton remodeling. Here we tested whether heat-shock protein 27 (HSP27), a small stress response protein involved in cytoskeletal remodeling, protects the kidney from tubulointerstitial fibrosis in obstructive nephropathy. Tubular cell HSP27 immunostaining was significantly increased in human kidneys with ureteropelvic junction obstruction, supporting the clinical relevance of our studies. To develop an animal model for mechanistic studies, we generated transgenic mice that specifically overexpress human HSP27 in renal tubules, under the kidney androgen-regulated protein promoter, and determined the effects of HSP27 overexpression on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis following unilateral ureteral obstruction. This was associated with decreased fibrogenesis as evidenced by significant declines in phosphorylated p38MAPK, collagen III, α-smooth muscle actin, 4-hydroxynonenal, and reduced trichrome staining following obstruction. Notably, E-cadherin and β-catenin remained at the cell membrane of tubular cells in transgenic mice with an obstructed ureter. Monocyte/macrophage infiltration, however, was not significantly affected in these transgenic mice. Thus, tubular HSP27 inhibits fibrogenesis in obstructive nephropathy. Further studies are needed to determine pathways regulating the interactions between HSP27 and the E-cadherin-β-catenin complex.

Acute fibrinous and organizing pneumonia (AFOP) has recently been identified as an unusual variant of acute lung injury. We describe a man with rapidly progressive lung disease who had AFOP detected via surgical lung biopsy. The patient acutely decompensated while in the hospital and required mechanical ventilation as well as a prolonged ICU stay. He responded poorly to initial treatment and progressively worsened, but he subsequently responded very well to combined therapy with mycophenolate mofetil and methylprednisolone. The combination of corticosteroids and mycophenolate may provide a safe and effective treatment strategy for severe forms of this newly defined pulmonary syndrome.

In mice and humans, the immunologic effects of developmental exposure to noninherited maternal antigens (NIMAs) are quite variable. This heterogeneity likely reflects differences in the relative levels of NIMA-specific T regulatory (T(R)) versus T effector (T(E)) cells. We hypothesized that maintenance of NIMA-specific T(R) cells in the adult requires continuous exposure to maternal cells and antigens (eg, maternal microchimerism [MMc]). To test this idea, we used 2 sensitive quantitative polymerase chain reaction (qPCR) tests to detect MMc in different organs of NIMA(d)-exposed H2(b) mice. MMc was detected in 100% of neonates and a majority (61%) of adults; nursing by a NIMA+ mother was essential for preserving MMc into adulthood. MMc was most prevalent in heart, lungs, liver, and blood, but was rarely detected in unfractionated lymphoid tissues. However, MMc was detectable in isolated CD4+, CD11b+, and CD11c+ cell subsets of spleen, and in lineage-positive cells in heart. Suppression of delayed type hypersensitivity (DTH) and in vivo lymphoproliferation correlated with MMc levels, suggesting a link between T(R) and maternal cell engraftment. In the absence of neonatal exposure to NIMA via breastfeeding, MMc was lost, which was accompanied by sensitization to NIMA in some offspring, indicating a role of oral exposure in maintaining a favorable T(R) > T(E) balance.

Advances in lung transplantation have improved 1-year survival rates, but allograft dysfunction continues to be a significant cause of post-transplant death. Diffuse alveolar damage is an early indication of allograft dysfunction and has been linked to gastroesophageal reflux. We report a case of diffuse alveolar damage-associated allograft dysfunction in a patient found to have significant non-acid gastroesophageal reflux.

Treating patients with kidney failure by organ transplantation has been extraordinarily successful. Although, current immunosuppressants have improved short-term allograft survival, most transplants are eventually lost due to chronic allograft nephropathy (CAN). The molecular mechanisms underlying CAN are poorly understood. Smooth muscle cells (SMC) play a major role in the pathogenesis of CAN by contributing to the thickening of the intima and narrowing of the lumen of blood vessels. We show that selenium-binding protein-1 (SBP-1), a protein implicated in protein trafficking and secretion, is localized primarily to SMC in vivo. SBP-1 was heavily tyrosine-phosphorylated in vivo. Remarkably, SBP-1 was absent or strongly downregulated in vascular SMC in monkey kidney allografts with CAN. In contrast, the SMC alpha-actin was strongly expressed in the vascular SMC of the same allografts, indicating that the decrease in SBP-1 was not due to a global decrease in SMC proteins. Out of four growth factors implicated in the pathogenesis of CAN, only TGF-beta blocked the expression of SBP-1; thus, TGF-beta could regulate the expression of SBP-1 in CAN. These results show that SBP-1 localizes primarily to SMC in vivo and implicate this phosphoprotein in the effects of TGF-beta on SMC and in the process of CAN.

Canine kidney preservation models have historically used autotransplants to avoid the complications of rejection, although clinically all transplants are allografts. This study investigated the effects of preservation time and method on early kidney function in a canine allograft vs. autograft model. Kidneys were harvested from beagles, preserved by cold storage (CS) in UW solution for 0, 24 or 72 h, or by machine perfusion (MP) with Belzer MPS for 72 h. In some experiments 45 min of warm ischemia (WI) was performed in situ before harvest. Allograft recipients received steroid immunosuppression. Kidney function was assessed by serum creatinine and survival for 7 days. Allografts preserved for 0 and 24 h performed as well as autografts. Allografts preserved for 72 h by either CS or MP had a higher incidence of primary nonfunction (PNF) compared with autografts, as determined by survival (50% vs. 100%, p < 0.003). Primary nonfunction kidneys had thrombotic microangiopathy, vascular and peritubular capillary binding of IgM and complement C4d, and evidence of circulating donor-specific antibodies; all consistent with humoral rejection. These responses were dependent on hypothermia time and were not attributable to ischemia, immunosuppression, preservation solution, or cellular rejection. In conclusion, prolonged hypothermia can cause PNF in allografts owing to acute humoral rejection.