Presence Of Interstitial Fibrosis Research Articles

Abrasion and dental pulp morphological changes in occlusal dysfunction.

The authors set out to assess if the presence and the degree of severity of the abrasion, as a consequence of the occlusal dysfunction, determine further morphological changes in the dental pulp. Study group included teeth dental pulp from 45 cases with occlusal dysfunction, subsequently divided into two subgroups: 24 cases with abrasion (AB) and 21 cases without abrasion (NONAB). The set of morphological parameters of dental pulp were thicknesses of the outer layer, inner layer and entire peripheral pulp zone, the presence of pulpal calcifications and their extent within the dental pulp, the presence of interstitial fibrosis and its extent within the dental pulp and the vascular density (VD) of pulpal capillary network. Tissue samples were fixed in 10% buffered formalin, embedded in paraffin, and sectioned off at 4 μm. Serial slides were stained with Hematoxylin-Eosin (HE), Masson's trichrome (MT) and anti-cluster of differentiation 34 (CD34) antibodies labeled with 3,3'-Diaminobenzidine (DAB) and transformed into virtual slides on which the above-mentioned parameters were studied comparatively with the help of a dedicated in-house software, realized in MATLAB (MathWorks, USA). The numerical values of the assessed parameters were also stratified in classes, thus obtaining score scales for each parameter. Statistical tools used were Lilliefors test, t-test (two-sample assuming equal variances), Mann-Whitney test, Pearson's correlation test, one-way analysis of variance (ANOVA) test and χ² (chi-squared) test. Both peripheral zone (PZ) and its layers individually tended to be thicker in the teeth with abrasion than in those without abrasion. Also, teeth with abrasion tended to develop larger amounts of calcium deposits in their dental pulp than teeth without abrasion. On the other hand, fibrotic tissue in dental pulp had no relationship with the presence or absence of abrasion. PZ as a whole and its layers evolved together in the same way, with a stronger correlation in the group of teeth without abrasion. Deposits of calcium evolved in the opposite direction to both the amount of fibrous tissue and the capillaries density of the dental pulp. Consequently, the amount of fibrous tissue and VD evolved together in the same way, more pronounced in the teeth without abrasion. Our preliminary study pointed out that different components of the dental pulp showed slight to moderate changes depending on the degree of abrasion in teeth with occlusal dysfunction.

Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL-6], C-reactive protein [CRP], von Willebrand factor [vWF], N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity Troponin T [hs-TnT], and Galectin-3 [Gal-3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty-six patients (15 with OSA and 41 non-OSA) were included in this hypothesis-generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01-12.92), and had significantly higher baseline levels of NT-proBNP (p = .044), vWF (p = .049), Gal-3 (p = .009), IL-6 (p = .002), and CRP (p = .003). This group presented lower levels of miR-21 and miR-208 (both p < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk.

ARHGDIB and AT1R autoantibodies are differentially related to the development and presence of chronic antibody-mediated rejection and fibrosis in kidney allografts

The role of non-HLA autoantibodies in chronic-active antibody-mediated rejection (c-aABMR) of kidney transplants is largely unknown. In this study, the presence and clinical relevance of non-HLA autoantibodies using a recently developed multiplex Luminex-based assay were investigated. Patients with a kidney allograft biopsy at least 6 months after transplantation with a diagnosis of c-aABMR (n = 36) or no rejection (n = 21) were included. Pre-transplantation sera and sera at time of biopsy were tested for the presence of 14 relevant autoantibodies.A significantly higher signal for autoantibodies against Rho GDP‐dissociation inhibitor 2 (ARHGDIB) was detected in recipients with c-aABMR as compared to recipients with no rejection. However, ARHGDIB autoantibodies did not associate with graft survival. Levels of autoantibodies against angiotensin II type 1-receptor (AT1R) and peroxisomal trans‐2‐enoyl‐CoA reductase (PECR) were increased in recipients with interstitial fibrosis in their kidney biopsy. Only the signal for AT1R autoantibody showed a linear relationship with the degree of interstitial fibrosis and was associated with graft survival.In conclusion, anti-ARHGDIB autoantibodies are increased when c-aABMR is diagnosed but are not associated with graft survival, while higher levels of AT1R autoantibody are specifically associated with the presence of interstitial fibrosis and graft survival.

Increased remote extracellular volume measured by CMR T1 mapping allows early identification of left atrial dysfunction in hypertrophic cardiomyopathy

Abstract Background Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM). Cardiac magnetic resonance (CMR) detects replacement fibrosis (RF) through late gadolinium enhancement (LGE) and interstitial fibrosis (IF) in apparently unscarred myocardium by T1 mapping-derived increased extracellular volume (ECV). Differently from LGE, to date only few small studies have explored the clinical significance of IF in HCM and a correlation between IF and diastolic dysfunction (DD) has been proposed. However, DD detection is challenging in this population since the accuracy of standard echocardiographic parameters is controversial, especially in presence of left ventricular outflow tract obstruction (LVOTO). Left atrial (LA) dysfunction is associated with high left ventricular (LV) filling pressures and may represent an early marker of DD in HCM. Purpose To explore the correlation between IF and LA dysfunction in HCM patients with preserved systolic function. Methods 93 consecutive HCM patients with preserved EF underwent a standard CMR scan. Semi-automatic threshold-based quantification of ventricular volumes, function and mass was performed. LA volumes (LAV) and function were evaluated by CMR feature-tracking (FT) analysis. The three atrial phasic functions were analyzed: (i) passive strain (εe), (ii) active strain (εa) and (iii) total strain (εs). LGE was quantified using the standard deviations (SDs) method (≥4 SDs). IF was assessed by T1 mapping-derived ECV quantification in remote myocardium (r-ECV). A matched group of 15 healthy subjects (HS) served as controls. Results Compared to HS, HCM patients showed increased LAV (LAV max: HS 39±9ml, HCM 59±20 ml; LAV min: HS 16±4 ml, HCM 34±17 ml; p&amp;lt;0.001), reduced LA EF (HS 61±3%, HCM 45±12%, p&amp;lt;0.001), impaired εs (HS 40±7%, HCM 29±11%, p&amp;lt;0.001) and εe (HS 26±7%, HCM 15±7%, p&amp;lt;0.001). No differences in εa were observed (HS 13±4%, HCM 14±7%, p 0.56). HCM patients were divided into 2 groups according to the presence of IF, defined as r-ECV values ≥29%. The two ECV groups did not differ in terms of LV EF, LA EF, LAV, LA area, E/E', LGE, LV mass, maximal wall thickness and LVOTO (all p&amp;gt;0.05). HCM patients with increased r-ECV showed significantly impaired LA function in terms of all three strain parameters vs. normal r-ECV group (HCM r-ECV &amp;lt;29%: εs 31±12%, εe15±7%, εa 15±5%; HCM r-ECV≥29%: εs 24±7%, εe 12±4%, εa 12±5%; all p&amp;lt;0.05). Conclusions In HCM patients increased r-ECV correlates with LA dysfunction, hinting towards a possible role for IF in determining altered LV relaxation and DD. LA strain in controls and HCM ECV groups Funding Acknowledgement Type of funding source: None

Expert recommendations for the diagnosis and treatment of interstitial lung disease caused by novel coronavirus pneumonia

COVID-19 is an acute infectious disease caused by a newly discovered coronavirus (SARS-CoV2). COVID-19 may manifest bilateral interstitial pneumonia on imaging. About 30%-60% of patients present varying degrees of interstitial changes, while most patients have a good prognosis. Since there's little practical instruct on treating interstitial lung disease (ILD) caused by COVID-19, we present this file as references for all the colleagues fighting with this disease. The primary findings on CT are bilateral, peripheral ground-glass opacities (GGO) and consolidation. Inter-/intra-lobular septal thickening are also common. Subpleural lines and traction bronchiectasis can be seen in some cases which indicate the presence of interstitial fibrosis. Images of severe cases are similar with those in advanced stage of nonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP). COVID-19 could present the typical two phases of diffuse alveolar damage: acute and proliferative phase on pathology. Massive pulmonary interstitial fibrosis may also be present. HRCT is the best radiological approach for the diagnosis and differential diagnosis of COVID-19, and to assess the presence of ILD. Periodical CT following-up is recommended for patients who present interstitial manifestations. Biomarkers such as KL-6, SP-D, RAGE may also helpful on evaluating the severity of interstitial fibrosis and therapeutic response. We do not suggest applying pulmonary function tests and 6-minute walking test on patients in active stage of the disease. The primary treatments in acute phase are antiviral therapy and supportive treatment. We do not suggest routine use of corticosteroids, while on patients with excessive activation of inflammatory response or rapid progression of lung lesions, a low to medium dosage of corticosteroids could be applied for a short course. Pirfenidone and Nintedanib are encouraged to apply on patients in reparative phase with evidence of progressing fibrosis. Low to medium dosage of corticosteroids is also feasible on patients with NSIP or OP manifestation in this phase, with a relatively longer course. Chinese traditional medicine and rehabilitation medicine may also helpful. Lung transplant surgery is an option for severe pulmonary fibrosis patients. Patients should receive CT following-up after be discharged from hospital, especially those whose pulmonary exudation is not well absorbed. We suggest a routine following-up on month 1, 4 and 10 after discharging, and an extended period for those who have developed irreversible interstitial fibrosis.

Peripheral type squamous cell carcinoma of the lung: clinicopathologic characteristics in comparison to the central type.

BackgroundSquamous cell carcinomas (SqCCs) of the lung are known to arise more often in a central area but reports of peripheral SqCCs have increased, with a pathogenesis that is obscured. In this study, the clinicopathologic characteristics of peripheral lung SqCCs were studied and compared with those of the central type.MethodsThis study included 63 peripheral lung SqCCs and 48 randomly selected central cases; hematoxylin and eosin-stained slides of surgically resected specimens were reviewed in conjunction with radiologic images and clinical history. Cytokeratin-7 immunohistochemical staining of key slides and epidermal growth factor receptor (EGFR)/KRAS mutations tested by DNA sequencing were also included.ResultsStages of peripheral SqCCs were significantly lower than central SqCCs (p=.016). Cystic change of the mass (p=.007), presence of interstitial fibrosis (p=0.007), and anthracosis (p=.049) in the background lung were significantly associated with the peripheral type. Cytokeratin-7 positivity was also higher in peripheral SqCCs with cutoffs of both 10% and 50% (p=.011). Pathogenic mutations in EGFR and KRAS were observed in only one case out of the 72 evaluated. The Cox proportional hazard model indicated a significantly better disease-free survival (p=.009) and the tendency of better overall survival (p=.106) in the peripheral type.ConclusionsIn peripheral type, lower stage is a favorable factor for survival but more frequent interstitial fibrosis and older age are unfavorable factors. Multivariate Cox analysis revealed that peripheral type is associated with better disease-free survival. The pathogenesis of peripheral lung SqCCs needs further investigation, together with consideration of the background lung conditions.

P0377THE RELATIONSHIP BETWEEN SEVERITY OF INTERSTITIAL FIBROSIS AND ANEMIA IN PATIENT WITH PRIMARY GLOMERULONEPHRITIS: THE DATA FROM TSN-GOLD WORKING GROUP

Abstract Background and Aims Anemia is one of the most important complications in chronic renal disease and inadequate erythropoietin production is the most important reason for anemia. Fibrosis of renal interstitium may be associated with inadequate synthesis of erythropoietin and anemia. In our study, we investigated the relationship between the severity of interstitial fibrosis (IF) in patients with primary glomerulonephritis (PGN) and anemia parameters. Method A total of 2794 patients who were recorded to the database of the Turkish Society of Nephrology, Glomerular Diseases (TSN-GOLD) Working Group between May 2009 and June 2019 were included in our national multicenter (44 centers) study. Patients aged 16 years or more with documented biopsy were included in the study. Patients were divided into four groups according to IF severity. IF was not detected in the interstitial area, was defined as none, if fibrosis was present in less than 25% of the area, defined as mild, if fibrosis was present in 25-50%, defined as moderate and if more than 50%, defined as severe. Anemia was defined as hemoglobin &amp;lt;12 g/dl in adult female patients and &amp;lt;13 g/dl in adult male patients, according to Clinical Practice Guidelines for anemia of CKD published by The Kidney Disease: Improving Global Outcomes Foundation. The relationship between IF severity and anemia parameters at the time of biopsy was investigated. Results In the study, 57% of the patients were male and their mean age was 41.0 ± 14.3 years. The mean eGFR was 82.7 ± 36.9 ml / min / 1.73 m2 and the hemoglobin level was 13.1 ± 1.9 g/dl. General characteristics of patients with and without anemia are given in Table 1. While 41.1% of patients had no IF, 41.2% had mild, 14.1% had moderate and 3.5% had severe IF. When the patients were divided into four groups according to the severity of IF, the mean hemoglobin and hematocrit levels were significantly different between the groups (Figure 1). Anemia was present in 960 patients (34.4%) (Figure 2). Anemia rate was significantly higher in the patients with IF than patients without IF (36.8% vs 30.9%, p = 0.001). Anemia rate was %25.1 in patients with eGFH≥60 ml/min/1.73m2 and 56% in patients with eGFR&amp;lt;60 ml/min/1.73m2. Gender, serum albumin, eGFR, proteinuria, presence of diabetes, presence of nephrotic syndrome, and presence of IF were the independent variables in the regression analysis of hemoglobin-related factors (Table 2). Conclusion Approximately one-third of PGN patients had anemia at the time of biopsy and the frequency of anemia increases in patients with IF. The presence of IF is an independent risk factor associated with the development of anemia in PGN. The elucidation of the etiopathogenesis of anemia in PGN patients may play an important role in the follow-up and treatment of patients. Studies on IF can play a critical role.

SAT-410 Clinicopathologic Features and Outcomes of Patients with Crescentic Glomerulonephritis with Renal Involvement: A Single-Center, 13-year Retrospective Study from Turkey

Crescentic glomerulonephritis (GN) is a group of the disease spectrum characterized by the presence of glomerular crescent formation as the principal histologic finding. We aimed to investigate the etiologic distribution and clinicopathologic features of the patients with biopsy-proven crescentic GN in the last 13 years in our center according to different percentages of crescents. Patients who had renal biopsy-proven glomerular crescent formation and recorded from 2005 to 2018 were retrospectively reviewed. The baseline clinical and laboratory parameters of all patients were obtained at the time of renal biopsy. Renal histopathological data were reviewed by light and immunofluorescence microscopy. According to the percentages of crescentic glomeruli, the patients were divided into three subgroups: group I (crescents <10%), group II (10%≤ crescents ≤30%) and group III (crescents >30%). The clinical, laboratory and histopathological features of patients, risk factors and outcomes were compared among the three groups. A total of 103 patients with biopsy-proven crescentic GN were included in the analysis and followed up. The results according to different percentages of crescents are presented in Table. As the percentage of crescentic glomeruli increased, it was associated with increased levels of baseline serum creatinine (p=0.018), lower baseline estimated glomerular filtration rate (eGFR) (p=0.002) and decreased macroscopic hematuria (p=0.032). In last outpatient clinic visit, eGFR, serum albumin and amounts of proteinuria were not different among the groups (p=0.096). The most common renal biopsy indications were rapidly progressive glomerulonephritis and nephrotic syndrome in all three groups (p=0.031). The disease spectrum of crescentic GN was as follows: 6 (6%) had anti-GBM GN, 16 (15.5%) had lupus nephritis, 27 (26%) had IgA nephropathy, 3 (3%) had infection-related GN, 5 (5%) had membranoproliferative GN, 42 (40.5%) had pauci-immune GN and 4 (4%) had others. There were no significant differences in the histological findings among the three groups except for mesangial cell proliferation and matrix expansion (p=0.002). Twenty three patients (%22.3) required dialysis on admission, including 6 (15%) patients with group II and 17 (36%) patients with group III (p<0.01). By the end of the follow-up period of 30 months, 35 (34%) patients progressed to end-stage renal disease (ESRD), requiring renal replacement therapy (7 (7%) renal transplantation and 28 (27%) dialysis) and 14 (13.5%) patients died. Cox regression analysis for renal survival showed that serum creatinine levels of 3.5 mg/dl or greater (HR= 1.5, 95% CI: 1.9-10.5, p<0.001) on admission and presence of interstitial fibrosis and tubular atrophy score >25% (HR= 2.7, 95% CI: 2-113, p=0.008) on renal biopsy were risk factors for ESRD. Of the etiologic spectrum of crescentic GN, pauci-immune GN had the poor renal and patient outcomes. This study provides valuable information about the disease spectrum of crescentic GN in our country. In patients with crescentic GN who present with different clinical features, an accurate and early diagnosis is essential for both renal and patient survival. Prognosis mostly depends on the degree of renal failure, histopathologic findings and the type of crescentic GN. Studies with larger sample sizes, including national registry data is still needed.

Shear wave elastography findings in Immunoglobulin A Nephropathy patients: is it more specific and sensitive for interstitial fibrosis or interstitial fibrosis/tubular atrophy?

Background Prediction of prognosis in Immunoglobulin A Nephropathy (IgAN) and taking appropriate precautions may reduce annual incidence of chronic kidney disease. This may be possible by close follow-up for the development and progression of interstitial fibrosis (IF) or interstitial fibrosis/tubular atrophy (IFTA) in IgAN patients. Aim To investigate whether Young’s elastic modulus (YM) which measured shear wave elastography (SWE) might be used for follow-up of IF or IFTA in IgAN patients. Methods Prospective study was approved by Human Research Ethics Committee. Group 1 consisted of patients with IgAN. Group 2 consisted of healthy control participants. Young’s elastic modulus which is a value of stiffness along with longitudinal stiffness was used to evaluate tissue elasticity. Specificity, sensitivity, positive predictive value (PPV) of YM for the presence of IF and IFTA were evaluated. Results Group 1 consisted of 30 participants, and group 2 consisted of 32 participants. Sensitivity and specificity of SWE to diagnose presence of IF for YM > 15 kPa were 89% and 90%, respectively. PPV among the ones whom IF was diagnosed by YM >15 kPa was 91%. Sensitivity and specificity of SWE to diagnose presence of IFTA for YM > 15 were 65% and 51%, respectively. PPV among the ones whom IFTA was diagnosed by YM >15 kPa was 78.1%. Conclusions YM which measured SWE is highly specific and sensitive in the diagnosis of IF, but not for IFTA in IgAN patients. Therefore, progression for IF in IgAN may be followed by SWE.

1047 Increased interstitial fibrosis in patients with mitral valve prolapse and mitro-annular dysjunction

Abstract Background in patients with myxomatous mitral valve prolapse (MVP), mitral annular disjunction (MAD) has been associated with the presence of late gadolinium enhancement (LGE) at papillary muscle level and the risk of sudden cardiac death. However, patients with MAD but no detectable LGE still may have arrhythmia. We investigated the relation between MAD and the presence of interstitial fibrosis in the basal inferior left ventricular myocardium. Methods 28 patient with MVP and associated MAD underwent Cardiovascular Magnetic Resonance imaging (CMR) at 1.5 T scanner (Aera, Siemens Medical Solutions, Erlangen, Germany). Exclusion criteria were ischemic heart disease, infiltrative cardiomyopathy and contraindication to CMR. 12 patients with mitral valve regurgitation but no MAD and 10 patients without mitral disease served as the control group. MAD severity was measured from LA wall-posterior MV leaflet junction to the top of the LV infero-basal wall during end systole. Insterstitial fibrosis was assessed by calculating the extracellular volume (ECV) from T1 mapping of the left ventricular basal slice acquired before and after Gadolinium injection. Results Mean age was 47,5+\-23,3 years and 60% were male. ECV was higher in patients with MVP compared with controls (basal septum: 0.27 ± 0.04 vs 0.23 ± 0.03 p = 0.006; basal inferoposterior wall 0.28 ± 0.03 vs 0.23 ± 0.02 p = 0.003) and there was a significant correlation between MAD severity and ECV of the basal inferior wall (spearman rho 0.68, p &amp;lt; 0.0001) (Figure 1). Among MVP patients, ECV of the basal inferoposterior wall was higher in patients positive for LGE in the papillary muscles (ECV 0.31 ± 0.03 vs 0.27 ± 0.03 p 0,004). Conclusion In MVP patients, MAD severity was associated with a higher amount of interstitial fibrosis even in the absence of detectable macroscopic fibrosis in the papillary muscle region. Abstract 1047 Figure 1

Changes in the telocyte/CD34+ stromal cell and α-SMA+ myoid cell networks in human testicular seminoma

Telocytes (TCs), also known as CD34+ stromal/interstitial cells, have recently been identified within the connective tissue of a variety of organs including the normal human testis. Testicular TCs appear to constitute a widespread reticular network distributed either in the peritubular or in the intertubular stromal spaces where they have been suggested to play different roles, such as participation to testis morphogenesis, postnatal preservation of the normal tissue/organ three-dimensional structure, and regulation of spermatogenesis and androgen hormone secretion and release. Although increasing evidence indicates that TCs may be involved in the pathophysiology of various diseases, no study has yet reported possible changes in these cells within the stromal compartment of seminoma, one of the most frequent malignant testicular cancers in humans. Therefore, here we carried out the first investigation of the presence and tissue distribution of TCs/CD34+ stromal cells in human testicular seminoma in comparison with normal human testis using either CD34 immunohistochemistry or CD34/CD31 and CD34/α-smooth muscle actin (α-SMA) double immunofluorescence analyses. In seminoma tissue sections, we observed an overall loss of TCs (CD34+/CD31− stromal cells) accompanying a severe degeneration of the normal architecture of seminiferous tubules and stromal tissue associated with dense cellularity increase and presence of interstitial fibrosis. Noteworthy, in the seminoma tissue the disappearance of TCs was paralleled by an expansion of α-SMA+ myoid cells. Moreover, the CD34+/CD31+ blood vessel network was greatly expanded, while steroidogenic Leydig cells were undetectable in seminoma specimens. Since TCs are emerging as important regulators of tissue and organ homeostasis, collectively the present findings indicate that the possible pathophysiologic implications of the loss of TCs in human testicular seminoma should not be further overlooked.

5. Isolated head drop: first symptom of anti-synthetase syndrome

IntroductionHead drop is an unusual clinical manifestation of myositis or neuromuscular weakness, and typically requires extensive investigation to identify the underlying pathology. Case report data are limited on this topic.Case descriptionA 72-year-old man with a background of extractable nuclear antigen (ENA) negative mixed connective tissue disease, trigeminal neuralgia, interstitial nephritis and ischaemic heart disease presented with an isolated head drop. On further prompting, he confirmed mild shortness of breath on exertion. He had sclerodactyly but no features of mechanic’s hands. Serum creatinine kinase was 1398 IU/L. Electromyography was myelopathic. Muscle biopsy taken from the neck was inconclusive. He had a strongly positive anti-nuclear antibody (ANA) test, and borderline myositis ENA panel result with borderline positive anti-EJ antibody.The myositis panel result prompted further investigation for underlying interstitial lung disease. Pulmonary function testing revealed a restrictive picture, with KCO of 82%. High resolution computed tomography showed areas of fine interstitial fibrotic change in all lobes.He was treated with a reducing course of oral prednisolone and 15mg weekly oral methotrexate with an excellent clinical response, with resolution of the head drop and normalisation of serum CK value. Repeat pulmonary function testing remains stable after 5 months.DiscussionThis is an unusual presentation of presumed anti-synthetase syndrome. As methotrexate had already been prescribed before the underlying lung pathology was identified with resulting excellent clinical response and stable respiratory symptoms, a multi-disciplinary decision was made to continue with this choice of disease modifying agent. The decision to use methotrexate in the presence of interstitial fibrosis is always difficult, and requires close liaison between rheumatology and respiratory colleagues.Key learning pointsPositive anti-synthetase antibodies should prompt further investigation for underlying interstitial lung disease. Head drop can be a first symptom of autoimmune myositis and warrants further investigation.Conflicts of interestThe authors have declared no conflicts of interest.

Predictors of Acute Kidney Injury in Deceased Kidney Donors After Brain Death

BackgroundDonors with acute kidney injury (AKI) are generally accepted as a valuable source of kidneys for transplant. The aim of this study was to assess the risk of developing AKI based on deceased kidney donor parameters. Materials and MethodsThe data of 162 kidneys procured from deceased donors after brain death were collected. These included clinical characteristics of donors and histologic assessment in organ biopsy specimens. The donors’ kidney terminal function was classified according to the Acute Kidney Injury Network criteria. All biopsies were performed with the use of a 16G automatic needle, and the 20-mm tissue specimen was available in all cases. Biopsy specimens were secured and prepared in a routine way with hematoxylin and eosin. The presence of chronic changes was analyzed according to the Banff 2009 classification by 1 experienced nephropathologist. The logistic regression model was used to assess the risk of AKI regarding donor characteristics and histologic findings. ResultsThere were 50 kidneys (30.9%) with AKI identified. The risk of AKI increased with donor age (P = .002; odds ratio [OR], 1.02; 95% CI, 1.01–1.03), body mass index (P = .003; OR, 1.05; 95% CI, 1.01–1.09), and male sex (P = .001; OR, 1.79; 95% CI, 1.31–2.27). Regarding the histologic findings, the interstitial fibrosis presence was a risk factor of AKI (P = .004; OR, 1.04; 95% CI, 1.01–1.06). ConclusionsOlder donor age, male sex, higher body mass index, and presence of interstitial fibrosis in kidney graft biopsy specimen are risk factors of AKI.

Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart.

This study investigates the impact of decreased fetal plasma glucose concentrations on the developing heart in late gestation, by subjecting pregnant ewes to a 50% global nutrient restriction. Late gestation undernutrition (LGUN) decreased fetal plasma glucose concentrations whilst maintaining a normoxemic blood gas status. LGUN increased the mRNA expression of IGF2 and IGF2R. Fetal plasma glucose concentrations, but not fetal blood pressure, were significantly correlated with IGF2 expression and the activation of CAMKII in the fetal right ventricle. LGUN increased interstitial collagen deposition and altered the protein abundance of phospho-PLB and phospho-troponin I, regulators of cardiac contractility and relaxation. This study shows that a decrease in fetal plasma glucose concentrations may play a role in the development of detrimental changes in the right ventricle in early life, highlighting CAMKII as a potential target for the development of intervention strategies. Exposure of the fetus to a range of environmental stressors, including maternal undernutrition, is associated with an increased risk of death from cardiovascular disease in adult life. This study aimed to determine the effect of maternal nutrient restriction in late gestation on the molecular mechanisms that regulate cardiac growth and development of the fetal heart. Maternal undernutrition resulted in a decrease in fetal glucose concentrations across late gestation, whilst fetal arterial PO2 remained unchanged between the control and late gestation undernutrition (LGUN) groups. There was evidence of an up-regulation of IGF2/IGF2R signalling through the CAMKII pathway in the fetal right ventricle in the LGUN group, suggesting an increase in hypertrophic signalling. LGUN also resulted in an increased mRNA expression of COL1A, TIMP1 and TIMP3 in the right ventricle of the fetal heart. In addition, there was an inverse relationship between fetal glucose concentrations and COL1A expression. The presence of interstitial fibrosis in the heart of the LGUN group was confirmed through the quantification of picrosirius red-stained sections of the right ventricle. We have therefore shown that maternal undernutrition in late gestation may drive the onset of myocardial remodelling in the fetal right ventricle and thus has negative implications for right ventricle function and cardiac health in later life.

Is there a correlation between kidney shear wave velocity measured with VTQ and histological parameters in patients with chronic glomerulonephritis? A pilot study.

To analyze the relationship between shear wave velocity in the kidney measured by point shear wave elastographyusing Virtual Touch Quantification (VTQ) (Siemens Acuson S2000) and histological parameters obtained from renal biopsies,in patients with chronic glomerulonephritis (CGN). The study group included 20 patients (meanage 47.95±13.59 years) with different types of CGN, that had underwent renal biopsy and 57 normal controls (mean age38.07±17.32 years). In all patients, five valid stiffness measurements were obtained in each kidney, with the patient in lateraldecubitus. Regarding the histological results, we assessed the presence or absence of glomerulosclerosis, interstitial fibrosis,and arteriolo-hyalinosis. In patients with CGN we obtained the following mean values of VTQ values: right kidney:2.12±0.81 m/s, left kidney 1.65±0.54 m/s, while in the normal controls significantly higher VTQ values were obtained: rightkidney 2.69±0.72 m/s (p=0.004), left kidney 2.48±0.73 m/s (p<0.0001). In patients with CGN no statistically significant correlationsbetween VTQ values and eGFR (r=0.37, p=0.12) or proteinuria (r=0.2, p=0.37) were found. We found significantlylower VTQ values in patients with interstitial fibrosis (1.46 vs. 1.99 m/s, p<0.05) and also in patients with arteriolo-hyalinosis(1.55 vs. 2.47 m/s, p<0.05). Our pilot study shows that shear wave velocity values in patients with CGN are significantlylower compared to normal controls, and there is a tendency to decrease with the decrease of eGFR, with the presenceof interstitial fibrosis and of arteriolo-hyalinosis.

Interstitial fibrosis in papillary thyroid microcarcinoma and its association with biological behavior.

Previous studies have revealed that fibrosis may affect the biological behavior of tumors, however associated research on papillary thyroid microcarcinoma (PTMC) is rare. The aim of the present study was to explore the association between interstitial fibrosis (IF) and the biological behavior of PTMC. In the present study, a total of 511 consecutive cases of PTMC were evaluated for the presence of IF and its association with clinical parameters and pathologic biomarkers. IF was identified in 340 of the 511 consecutive cases and it was significantly associated with the age (P=0.033), tumor diameter (P=0.017) and lymphocytic metastasis (P<0.001) of the patient. There were significantly more female in the fibrosis group than in fibrosis-absent group (P=0.024). In the analysis of clinical biomarkers using immunohistochemistical staining, IF was significantly associated with cytokeratin 19 (P=0.008) and galectin-3 (P=0.022). Analysis of patient outcomes indicated that IF was an independent prognostic factor of recurrence (hazard ratio = 2.181; 95% confidence interval = 1.163–4.090; P=0.015). These findings suggest that the combined effect of a patient's age, sex and tumor size may potentially contribute to fibrotic lesions and IF was a factor contributing to poor prognosis in patients with PTMC.

Clinicopathological correlation and treatment response of primary focal segmental glomerulosclerosis in adults and adolescents.

The incidence of focal segmental glomerulosclerosis (FSGS) is approximately 10% in children <6 years, 20% in adolescents, and 20-25% in adults. A retrospective observational study was done to document clinicopathological correlation, treatment response, and risk factors in the progression of chronic kidney disease (CKD) of primary FSGS in adults and adolescents. A total of 170 patients were studied with a mean follow-up of 4.32 ± 1.2 years. FSGS not otherwise specified was the most common subtype (56%) followed by tip variant (24%). About 32% had complete remission (CR) at a mean time of 6.4 months, 23% had partial remission (PR) at a mean time of 5.7 months, and 45% had no response to steroids. Persistent nephrotic proteinuria at 3rd and 6th month and presence of interstitial fibrosis and tubular atrophy >30% in renal biopsy are the independent predictors of poor response to treatment. Presence of anemia, interstitial fibrosis, and tubular atrophy of >30% in renal biopsy and the absence of remission after treatment were the independent predictors of CKD progression. Overall renal survival was 78% at 3 years and 54% at 5 years. Renal survival difference with or without nephrotic proteinuria at onset was 39% and 69% at 5 years. Renal survival was higher in patients with normal renal function (66%) compared with those who had renal failure (42%) at 5 years. Renal survival at 5 years for CR was 69%, PR was 49%, and no remission was 42%.

Development and validation of a prognostic index for allograft outcome in kidney recipients with transplant glomerulopathy

We studied 92 patients with transplant glomerulopathy to develop a prognostic index based on the risk factors for allograft failure within five years of diagnosis (Development cohort). During 60 months (median) follow up, 64 patients developed allograft failure. A chronic-inflammation score generated by combining Banff ci, ct and ti scores, serum creatinine and proteinuria at biopsy, were independent risk factors for allograft failure. Based on the Cox model, we developed a prognostic index and classified patients into risk groups. Compared to the low risk group (median allograft survival over 60 months from diagnosis), patients in the medium risk group had a hazard ratio of 2.83 (median survival 25 months), while those in the high risk group had a hazard ratio of 5.96 (median survival 3.7 months). We next evaluated the performance of the prognostic index in an independent external cohort of 47 patients with transplant glomerulopathy (Validation cohort). The hazard ratios were 2.18 (median survival 19 months) and 16.27 (median survival 1.6 months), respectively, for patients in the medium and high risk groups, compared to the low risk group (median survival 47 months). Our prognostic index model did well in measures of discrimination and calibration. Thus, risk stratification of transplant glomerulopathy based on our prognostic index may provide informative insight for both the patient and physician regarding prognosis and treatment.

Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency--histologic and immunohistochemical analyses of 16 cases.

Common variable immunodeficiency is a primary immunodeficiency of unknown etiology characterized by low serum immunoglobulin G, a decreased ability to make specific antibodies, and variable T-cell defects. Approximately 10-30% of patients with common variable immunodeficiency develop clinical evidence of a diffuse parenchymal lung disease with a constellation of histopathologic findings termed granulomatous and lymphocytic interstitial lung disease. In this study, we characterized the histologic and immunohistochemical features in a series of 16 cases diagnosed by open lung biopsy. Peribronchiolar and interstitial lymphocytic infiltration, granulomatous inflammation, and organizing pneumonia were consistent features; interstitial fibrosis with architectural remodeling was also found in a subgroup of patients. By immunohistochemistry, a predominance of CD4+ T lymphocytes with variable numbers of CD8+ T cells and B cells was present, with a striking absence of FOXP3-positive T-regulatory cells. This heretofore unrecognized immunohistochemical finding needs further investigation for a potential role in the pathogenesis of the condition. The presence of interstitial fibrosis with or without architectural remodeling in a subset of patients also needs additional study, for effect on prognosis.

Pattern, clinical features and response to corticoids of glomerular diseases in a Brazilian population. An analytical cross-sectional study.

Glomerular disease registries are increasing all around the world. The aim of this study was to evaluate the clinical characteristics and treatment response among patients with glomerular diseases followed up in a tertiary hospital in Brazil. Analytical cross-sectional study; tertiary-level public hospital. This study included patients with glomerular diseases followed up at a tertiary hospital in Fortaleza, northeastern Brazil. Clinical and laboratory data on each patient were registered. The response to specific treatment was evaluated after 3, 6 and 12 months. The study included 168 patients of mean age 37 ± 14 years. The most prevalent glomerular diseases were focal segmental glomerulosclerosis FSGS] (19.6%), minimal change disease MCD] (17.9%), membranous nephropathy MN] (16.7%) and lupus nephritis LN] (11.9%). The main clinical presentations were nephrotic proteinuria (67.3%) and renal insufficiency (17.9%). The mean proteinuria value decreased after the treatment began. Regarding 24-hour proteinuria on admission, there was no significant difference between patients with a good response and those with no response (7,448 ± 5,056 versus 6,448 ± 4,251 mg/24 h, P = 0.29). The glomerular disease with the highest remission rate was MCD (92%). Absence of interstitial fibrosis presented a strong correlation with remission (remission in patients without fibrosis = 83.4% versus 16.3% in those with fibrosis, P = 0.001). The present study found that the most frequent glomerular disease was FSGS, followed by MCD, MN and LN. The presence of interstitial fibrosis was a predictor of poor therapeutic response.