Organ Biopsy Research Articles

Primary cardiac amyloidosis.

Cardiac amyloidosis - the disease which is characterized by deposition of insoluble protein amyloid in intercellular space is one of the most severe implications of systemic amyloidosis. Primary cardiac amyloidosis possesses a wide range of clinical implications that complicates well-timed diagnostics and, respectively, treatment. The long latent current and the adverse forecast do extremely important diagnostics of cardiac amyloidosis at early stages of a disease. The modern concept of pathogenesis and morphology of an amyloidosis is covered in article, the clinical options of a current, diagnostic methods of dysfunction of heart including bio- and immunochemical blood analysis and urine, a complex of tool methods of a research and «the gold standard» of verification of deposits of amyloid - a biopsy of various organs and tissues are described.

Laparoscopy: a challenge for surgeons, benefit for patients

Laparoscopy is commonly referred to as keyhole surgery. Operational techniques based on laparoscopy have been widely applied in humans, and recently also in veterinary medicine, with a wider application. Laparoscopy is a minimally invasive surgical technique for viewing various abdominal organs like adrenal gland, spleen, kidney, ovaries, gallbladder, bile ducts, liver and intestines. The most common indications for laparoscopy in animals are: biopsy of abdominal organs or abdominal tissue masses, as well as surgical operations such as: gynaecological procedures, cholecystectomy, adrenalectomy, nephrectomy, hernia repair, bowel resection and vasoligation. Therefore, the same surgical interventions in traditional surgery can be performed by this innovative surgical technique: minimally invasive surgery.

A bioequivalence evaluation of long-chain triacylglycerol/medium-chain triacylglycerol emulsion in beagle dogs

Objective Long-chain triacylglycerol(LCT) by three producers, each mixed with the same medium-chain triacylglycerol(MCT), were compared with the brand MCT/LCT in causing focal necrosis of hepatocytes in beagle dogs (a bioequivalence evaluation). Methods 21 beagle dogs (male, 0.7-1.5 years old, 10-15 kg) were used in this study. According to the sources of the LCT, the animals were divided into Group A (LCT made in China), Group B (LCT made in Japan), Group C (LCT made in Germany), and the control group (the brand 10% MCT/LCT). Central venous port was placed via the lumber vein of the animals under general anesthesia. After 2 weeks of rehabilitation, MCT/LCT was administered through this port for 28 days at 9 g/(kg·d)[while the routine dose used clinically was 1 g/(kg·d)]. The laboratory indexes and the pathomorphism of the liver and kidney were studied single blindly. Results Laboratory tests, including liver and kidney function, blood coagulation function and lipid metabolism, did not identify differences among emulsions with different sources of LCT. Liver biopsy at day 28 showed no focal necrosis in Group C and the control group; there was minor damage in Group B; and Group A had obvious liver necrosis. and the pathological findings of other organs are similar. No significant difference was observed in biopsies of other organs. Conclusions Emulsions with different sources of LCT varied in their damage to the liver. Generics with LCT of higher quality were equivalent to the brand MCT/LCT in terms of safety. Key words: Equivalence evaluation; Fat emulsions, intravenous; Long-chain triacylglycerol; Medium-chain triacylglycerol; Safety study

Tailored interactive sequences for continuous MR-image-guided freehand biopsies of different organs in an open system at 1.0 tesla (T) - Initial experience.

To assess the feasibility, image quality, and accuracy of freehand biopsies of liver, bone, muscle, vertebral disc, soft tissue, and other lesions using balanced steady-state free precession (SSFP, balanced fast field echo: bFFE), spoiled and nonspoiled gradient echo (FFE), and turbo spin echo (TSE) sequences for interactive continuous navigation in an open magnetic resonance imaging (MRI) system at 1.0 tesla (T). Twenty-six MR-guided biopsies (five liver, five bone, four muscle, four vertebral disc, one lung, one kidney, one suprarenal gland, and five soft or other tissue) were performed in 23 patients in a 1.0-T open magnetic resonance (MR) scanner (Panorama HFO, Philips Healthcare, Best, the Netherlands). A total of 42 samples were obtained. Depending on lesion size and location, 14-18-gauge MR-compatible biopsy sets with a length of 100 or 200 mm (Somatex Medical, Teltow, Germany), 14-18-gauge MR-compatible semiautomatic biopsy guns with a length of 100 or 150 mm (Invivo, Schwerin, Germany), or 11-gauge MR-compatible bone marrow biopsy needles with a length of 100 mm (Somatex Medical, Teltow, Germany) were employed. All lesions were visible with continuous interactive imaging. Our initial results indicate that bFFE is particularly suitable for fast-moving organs (pulmonary, paracardial); moving organs are targeted better with T1-weighted (T1W) TSE, T1W FFE (liver) or T2-weighted (T2W) TSE (complicated cysts, adrenal glands), and static organs are successfully approached with proton density (PD) (spine) or T1W TSE (peripheral bones, musculoskeletal system). No adverse events related to the use of MRI were obtained. No complications occurred according to the Society of Interventional Radiology (SIR) clinical practice guidelines. Applying tailored interactive dynamic imaging sequences for continuous navigation to liver, bone, muscle, vertebral disc, soft tissue, and other lesions can improve the feasibility, image quality, and interventional accuracy of freehand MR-guided biopsies and may hence reduce the risk of complications.

Minimally invasive small intestinal exploration and targeted abdominal organ biopsy with a wound retraction device in 42 cats (2005-2015).

To describe the surgical technique and evaluate short-term outcome after minimally invasive small intestinal exploration and targeted organ biopsy with a wound retractor device (WRD) in cats. Multi-institutional retrospective study. Forty-two cats. A wound retractor was inserted into the abdomen on the ventral midline through a 2-4 cm incision at the level of the umbilicus. Short segments (6-10 cm long) of intestinal tract were sequentially exteriorized and explored through the WRD. Full thickness, small intestinal biopsies were obtained extracorporeally via the WRD. A commercially available single-port device was inserted through the WRD for laparoscopic exploration of the abdomen. The majority of the small intestine could be exteriorized and explored through the WRD. In all cases, full thickness biopsies of the small intestine of diagnostic quality were obtained. The most common histological findings were inflammatory bowel disease (n = 16), intestinal lymphoma (n = 14), and eosinophilic enteritis (n = 7). Two cases required conversion to a traditional open laparotomy due to abdominal pathology diagnosed after placement of the WRD (abdominal adhesions and need for a splenectomy). Postoperative complications occurred in 4 of 39 cats (10.3%), leading to 2 deaths after discharge from the hospital. MISIETB with a WRD alone or combined with laparoscopy is a safe technique for small intestinal exploration and targeted abdominal organ biopsy in cats. Single-port laparoscopy can effectively be performed through the WRD for complete abdominal exploration and biopsy of abdominal organs.

P048 NGS performance on a transplanted liver biopsy sample: A case study

A male pediatric patient was diagnosed with biliary atresia and was transplanted with liver from a deceased donor. The surgery went well, but years later the patient developed antibodies to Cw12, DR14, DQ7 and DQA1∗04:01 and various DP alleles. The need for high resolution typing to determine the identity of de novo DSA and the lack of any remaining pre-transplant sample on a deceased donor led to the use of NGS to determine chimeric typing. Genomic DNA was extracted from a post-transplant liver biopsy from this patient by using Gentra Puregene Tissue kit. We used the Immucor NGS FLEX HLA typing system for amplification and sequencing of HLA genes HLA -A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPA1, and DPB1 followed by analysis with MIA FORA software. The NGS methodology is a clonal sequencing approach which solves the phase ambiguity problems inherent with Sanger-based sequencing when alleles are amplified and sequenced together. The genomic DNA extracted from the transplanted liver biopsy is chimeric, with residual recipient DNA at very low but detectable levels. The presence of chimeric reads is the result of co-amplification of both donor and recipient HLA genes. The majority of sequencing reads with zero mismatches belonged to the donor and were concordant with the deceased donor HLA type provided by UNOS. Unclaimed sequencing reads appeared as grey background and derived from the recipient HLA type (previously obtained with pre-transplant samples). In this case and a few other chimeric cases examined in our laboratory, the MIA FORA NGS software detected the HLA type of donor as the called alleles and showed some unclaimed reads that did not align to the donor type but rather to the HLA type of recipient. We note that if the donor and recipient HLA genes are perfectly matched in one or both alleles then they are indistinguishable. The clonal sequencing nature of the NGS reveals PCR primer specificity by identifying the sequences of all co-amplified genomic regions within the intended target region in the same biopsy sample. This case demonstrates the clinical utility of high resolution HLA typing by NGS technology in the clinical setting to de convolute a solid organ biopsy admixture i.e. the ability to do chimeric typing.

Concurrent biopsies of both grafts in recipients of simultaneous pancreas and kidney demonstrate high rates of discordance for rejection as well as discordance in type of rejection - a retrospective study.

It is commonly assumed that in simultaneous pancreas and kidney (SPK) recipients, rejection of the two organs is concordant. As a result, concurrent biopsies of both organs are rarely performed and there are limited histological data on how often rejection is in fact discordant. We reviewed all SPK recipients transplanted at the University of Wisconsin between January 01, 2001, and December 31, 2016, that underwent biopsy of both organs. We included all patients whose biopsies were within 30 days. If patients were treated for rejection between biopsies, they were excluded if the biopsies were more than 4 days apart. Ninety-one simultaneous biopsies were performed within 30 days of each other, and 40 met our inclusion criteria. A total of 25 (62.5%) patients had concordance of biopsy findings: 11 had rejection of both organs, and 14 had no rejection of either organ. The other 15 (37.5%) were discordant for rejection, with 10 having pancreas-only rejection and five kidney-only rejection. It was striking to find that four of the 11 patients with concordance for rejection (36%) had different types (AMR, ACR, or mixed) of rejection in the two organs. This large series of simultaneous pancreas and kidney biopsies demonstrates the continued utility of performing biopsies of both organs.

Identifying independent risk factors for graft loss after primary liver transplantation.

The aim of the study is the identification of independent risk factors for re-transplantation after primary liver transplantation beyond the occurrence of hepatic artery thrombosis. Eight hundred thirty-four adult patients undergoing primary liver transplantation were analyzed. A propensity score was developed using multivariable binary logistic regression with hepatic artery thrombosis as the dependent variable. The logit link function of the propensity score was included into multivariable Cox regression analysis for graft survival to adjust the study population. Graft loss was observed in 134 patients (16.1%). Independent significant risk factors for graft loss were recipient platelet count (p=0.040; HR: 1.002; 95%-CI: 1.000-1.003), preoperative portal vein thrombosis (p=0.032; HR: 1.797; 95%-CI: 1.054-2.925), donor age (p<0.001; HR: 1.026; 95%-CI: 1.012-1.040), percentage of macrovesicular steatosis of the graft (p=0.011; HR: 1.037; 95%-CI: 1.009-1.061), early complications leading to revision surgery (p<0.001; HR: 2.734; 95%-CI: 1.897-3.956), duration of the transplant procedure (p<0.001; HR: 1.005; 95%-CI: 1.003-1.007) as well as transplantation of a split liver graft (p=0.003; HR: 2.637; 95%-CI: 1.420-4.728). The logit of the propensity score did not reach statistical significance in the final multivariable Cox regression model (p=0.111) indicating good adjustment for the occurrence of hepatic artery thrombosis. Liver transplant programs might benefit from regular donor organ biopsies to assess the amount of macrovesicular steatosis. An elevated recipient platelet count can promote reperfusion injury leading to graft loss. A liver graft from an elderly donor should not be split or be transplanted in a recipient with detected portal vein thrombosis.

Overuse of organ biopsies in immunoglobulin light chain (AL) amyloidosis: The consequence of failure of early recognition.

e19532 Background: The diagnosis of amyloidosis requires histological confirmation of Congo-red (CR) deposits. The tissue source is preferably fat and/or bone marrow biopsy, but at times organ biopsy is required. Methods: We studied 612 patients with systemic light chain amyloidosis to characterize the tissues used to establish the diagnosis Results: The median number of tissue samples biopsied for CR staining was 3. Ninety-five percent of bone marrow (BM) biopsies were stained for CR, while 79% of patients had fat aspiration performed for CR staining. Overall, 76% of patients underwent both procedures. CR stain sensitivity was 69% in BM samples, 75% in fat aspiration and in 89% for both sources combined. CR stain sensitivity was 97-100% for heart, renal and liver biopsies. 42% of patients with renal involvement, 21% of patients with liver involvement and 13% of patients with heart involvement underwent organ biopsy, when a less invasive safer biopsy would have established the diagnosis. Predictors of need for organ biopsy were male sex, limited organ involvement and lack of fat aspiration (Table). Conclusions: Fat aspiration is underutilized for histologic confirmation of amyloidosis. Organ biopsies (particularly renal biopsies) were performed at a high rate, which represents a failure to recognize the disease (i.e. failure to screen with a light chain assay etc.). Early awareness of amyloidosis in the differential diagnosis of patients with organ dysfunction may lead to fewer unnecessary organ biopsies [Table: see text]

Smears are important for adequate cytologic diagnosis of kidney lesions

Traditionally at our institution, smears with or without liquid-based cytology (LBC) and core biopsies (CBs) have been obtained by radiologists performing image-guided fine-needle aspiration biopsies (FNABs) of deep organs. Since 2015, however, there has been a shift to providing cytology with samples for LBC only when obtaining CBs. The impression among our institution's cytologists is that LBC alone is less often adequate for diagnosis compared with smears and LBC together. We examined a series of kidney FNABs pre- and post-"LBC only" to evaluate this impression. With institutional review board approval, we compared all kidney FNABs from 2012 to those from 2015. We recorded the type(s) of cytology preparation(s), the number of cytology slides, the cytology diagnosis, the concurrent CB diagnosis, and whether there was a subsequent excision and the excision diagnosis. We examined cytology and CB slides as needed. In 2012, 105 patients underwent 111 kidney biopsies, 109 with smears made. In 2015, 58 patients underwent 62 kidney biopsies, 7 with smears made. In 2012, there were 13 (12%) nondiagnostic (ND) cytology cases and 19 (17%) cases where the cytology and CB diagnoses were discrepant. By comparison, in 2015, there were 20 (32%) ND cytology cases and 21 (33%) discrepant cases. There were more cytology slides per case and fewer ND diagnoses in 2012 compared with 2015 (12% versus 32%, respectively, P = 0.001). Concordance was also better in 2012 (83% versus 67%, P = 0.015). We believe that our metrics would improve if we returned to the procedures followed in2012.

Overuse of organ biopsies in immunoglobulin light chain amyloidosis (AL): the consequence of failure of early recognition

Introduction: The diagnosis of amyloidosis requires histological confirmation of Congo-red (CR) deposits. The tissue source is preferably fat aspiration and/or bone marrow (BM) biopsy, but at times organ biopsy is required.Methods: We studied 612 patients with systemic immunoglobulin light chain amyloidosis to characterise the tissues used to establish the diagnosis.Results: The median number of tissue samples was 3. About 95% of BM biopsies were stained for CR, while 79% of patients had fat aspiration CR-stained. CR stain sensitivity was 69% in BM, 75% in fat aspiration and 89% for both sources combined. In comparison, CR sensitivity was 97–100% for heart, renal and liver biopsies. About 42% of patients with renal involvement, 21% of patients with liver involvement and 13% of patients with heart involvement underwent organ biopsy, when a less invasive biopsy would have established the diagnosis. Predictors for the requirement for organ biopsy were male sex, limited organ involvement and lack of fat aspiration.Discussion: Fat aspiration is underutilised for histologic confirmation of amyloidosis. A high rate of organ biopsies represents a failure to recognise the disease. Early awareness of amyloidosis in patients with organ dysfunction may lead to more judicious use of organ biopsies in this disease.Key messagesFat pad aspiration is underutilised to establish the diagnosis of amyloidosis.Bone marrow and fat pad aspiration obviates the need for invasive biopsies.The excessive use of organ biopsy in AL amyloidosis reflects failure to recognise the disease early in its course.

Burdensome Research Procedures in Trials: Why Less Is More.

A large volume of trials involve invasive, nontherapeutic research procedures, like organ biopsy or sham surgeries, that can pose risks comparable with the experimental treatment itself but that have no direct benefit for volunteers. Though such procedures can enhance the value of clinical investigations, recent studies suggest that many studies involving invasive, nontherapeutic research procedures are not well planned and reported; some studies suggest that their results are often not utilized in the planning of new investigations. This commentary offers recommendations for how investigators, sponsors, and ethics committees might improve evaluation and implementation of studies involving invasive nontherapeutic procedures. We conclude by urging more demanding scientific standards for the rationale, design, and reporting of burdensome, nontherapeutic research procedures-particularly where they involve risk of serious complications.

Selection of Biopsy Site for Patients with Systematic Amyloidosis.

Objective To evaluate the sensitivities of various biopsy methods for the diagnosis of systematic amyloidosis (SA). Methods The clinical data and biopsy results of 194 SA patients who were treated in Peking Union Medical College Hospital from January 2009 to June 2015 were retrospectively analyzed. Results The highest sensitivity was achieved by biopsy of affected organs,with renal biopsy 97.4%,heart biopsy 95.0% and liver biopsy 87.5%. Among non-invasive biopsy methods,tongue biopsy was found to be 75% sensitive,followed by gingiva biopsy at 57%,abdominal fat pad aspiration at 57%,rectum biopsy at 16%,and bone marrow examination at 8%. Combination of tongue and abdominal fat pad biopsy yielded a detection rate of 93.1%. Conclusions Biopsy of the involved organ has the highest sensitivity. However,combination of multiple non-invasive biopsy methods may has sensitivity comparable to organ biopsy and is safer and more convenient.

Immunoglobulin light chain amyloidosis: 2016 update on diagnosis, prognosis, and treatment.

Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, peripheral/autonomic neuropathy, and atypical multiple myeloma. Tissue biopsy stained with Congo red demonstrating amyloid deposits with applegreen birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. N-terminal pro-brain natriuretic peptide (NTproBNP), serum troponin T, and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months. All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure of involved sites. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include systolic blood pressure >90 mmHg, troponin T <0.06 ng mL21, age <70 years, and serum creatinine 1.7 mg dL21. Nontransplant candidates can be offered melphalan-dexamethasone or cyclophosphamide-bortezomib-dexamethasone. Other combinations of chemotherapy with agents such as cyclophosphamide-thalidomide (or lenalidomide)-dexamethasone, bortezomib-dexamethasone, and melphalan-prednisone-lenalidomide have documented activity. Antibodies designed to dissolve existing amyloid deposits are under study for previously treated and untreated patients. Late diagnosis remains a major obstacle to initiating effective therapy. Am. J. Hematol., 2016. © 2016 Wiley Periodicals, Inc. Am. J. Hematol. 91:948-956, 2016. © 2016 Wiley Periodicals, Inc.

Mitochondrial dysfunction in peripheral blood mononuclear cells in early experimental and clinical acute pancreatitis

Background/objectivesMitochondrial dysfunction occurs in vital organs in experimental acute pancreatitis (AP) and may play an important role in determining severity of AP. However, obtaining vital organ biopsies to measure mitochondrial function (MtF) in patients with AP poses considerable risk of harm. Being able to measure MtF from peripheral blood will bypass this problem. Furthermore, whether mitochondrial dysfunction is detectable in peripheral blood in mild AP is unknown. Therefore, the objective was to evaluate peripheral blood MtF in experimental and clinical AP. MethodMitochondrial respiration was measured using high resolution oxygraphy in an experimental study in caerulein induced AP and in a separate study, in patients with mild AP. Superoxide, cytochrome c, mitochondrial membrane potential (ΔΨ) and adenine triphosphate (ATP) were also measured as other markers of MtF. ResultsEven though some states of mitochondrial respiration were increased in both experimental and clinical AP, this did not lead to an increase in net ATP in patients with AP. The increased leak respiration in both studies was further proof of dyscoupled mitochondria. In the clinical study there were also features of mitochondrial dysfunction with increased leak flux control ratio, superoxide, ΔΨ and decreased cytochrome c. ConclusionThere is evidence of mitochondrial dysfunction with dyscoupled mitochondria, increased superoxide and decreased cytochrome c in patients with mild acute pancreatitis. Further studies should now determine whether mitochondrial function alters with severity in AP and whether mitochondrial dysfunction responds to treatments.

The performance of telescoping fat pad biopsies for detecting systemic amyloidosis: a four and a half year retrospective analysis and brief review of the fine needle aspiration literature.

Systemic amyloidosis has historically been diagnosed by organ biopsy and Congo red staining, with reported sensitivities that exceed 90%. The abdominal fat pad fine needle aspiration (FNA), introduced in the 1970's, carries sensitivity estimates largely derived from studies with deficiencies. Patient follow-up is often unclear and proportionally low numbers of patients are verified as true negatives. Issues in other studies include only testing verified systemic amyloidosis cases. The telescoping fat pad biopsy (TFPB) is used as an alternative to FNA and is similarly carried out quickly with low morbidity. Although the two methods would seem to be comparable intuitively, this has not been established because sensitivity data for the TFPB method is scarce to non-existent. The charts of 58 consecutive patients who underwent TFPB screening for amyloidosis in a single hospital from August of 2010 to January 2015 were examined. All six TFPB positive patients were determined to be true positives. Eight TFPB negative patients were concurrently determined to have systemic amyloidosis by other methods - organ biopsy (7) and mass spectrometry (1) resulting in a 43% sensitivity. The remaining patients were categorized into 25 true negatives and 18 that were indeterminate based on clinical course and other biopsy results.

Analysis of diagnostic and therapeutic strategies in advanced cardiac light-chain amyloidosis

Prognosis of advanced cardiac light-chain amyloidosis (ACAL) is ominous. Diagnosis of ACAL is frequently preceded by several biopsies of non-clinically affected tissues, which can result in dangerous treatment delays. Combinations of alkylators and steroids have a limited role in its therapy. Definitive efficacy of bortezomib in ACAL is not widely described. In this study we analyze the diagnostic yield of biopsies and compare the effect of bortezomib with other therapeutic strategies in ACAL patients. This study is a retrospective analysis of 40 consecutive ACAL patients treated at our hospital (2005 to 2015). For comparison purposes, the cohort was divided into 2 groups: patients treated with bortezomib (n = 23) and those treated with other therapeutic approaches (non-bortezomib, n = 8). Sensitivity of biopsies of non-clinically affected organs was 23%, as compared with 97% for affected organ biopsies (p < 0.0001). The need for >2 biopsies resulted in an average delay in diagnosis of 4.1 months (p = 0.007). Hematologic response was observed in 96% of patients in the bortezomib group compared with 25% in the non-bortezomib group (relative risk = 3.8; 95% confidence interval 1.14 to 12.75; p = 0.0002). Cardiac response criteria were met by 60% of patients in the bortezomib group as compared with none in the non-bortezomib group (p = 0.005). Survival at 6 months and 1 and 2 years for bortezomib patients was 91%, 91% and 73%, as compared with 58%, 15% and 0% for non-bortezomib patients (log rank, p < 0.0001), respectively. In our experience, the sensitivity of biopsies from non-affected organs in ACAL is poor and could result in diagnostic delay. Bortezomib was associated with higher hematologic and cardiac response rates as well as survival when compared with other therapies.

Diagnostic Laparoscopic Biopsy in Dogs and Cats

Se-Jin Park, Seung-Yong Lee, So-Young Jin, Min-Hyang Kim, Seong-Hoon Seok, Young-Ki Kim, Hee-Chun Lee, Dong-In Jung, Il-Hwa Hong, Seong-Chan Yeon. J Vet Clin 2016;33:21-4. https://doi.org/10.17555/jvc.2016.02.33.1.21

Distribution of miRNA expression across human tissues.

We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10−8) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas).

Arthrogryposis-renal tubular dysfunction-cholestasis syndrome: a cause of neonatal cholestasis. Case report

Arthrogryposis-renal dysfunction-cholestasis syndrome is a rare lethal disorder that involves multipl organ system. It is inherited autosomal recessive and caused by defects in the VPS33B and VIPAR genes. Three cardinal findings of this syndrome are arthrogryposis, renal tubular dysfunction and cholestasis.The other organ involvements including ichthyosis, central nervous system malformation, platelet anomalies, congenital heart defects and severe failure to thrive are sometimes associated with this syndrome. Clinical findings, organ biopsy and mutational analysis can help for diagnosing but there is no curative treatment except supportive care. Several symptoms of this condition are already usually present in the neonatal period: arthrogryposis, neonatal cholestasis, skin lesions, among others. Usually survival is until the first year of life. We present a newborn whose evolution was rapidly fatal.