All optical neural interfaces.

Brain/computer interfaces (BCIs) rely on the concurrent recording of many channels of electrical activity from excitable tissue. Traditionally such neural interfacing has been performed using cumbersome, channel-limited multielectrode arrays. We believe that BCIs can greatly benefit from using an optical approach based on simple yet powerful liquid-crystal based transducer technology. This approach potentially offers a technology platform that can sustain the necessary bandwidth, density of channels, responsivity, and conformability that are required for the long-term viability of such interfaces. In this paper we review the overall architecture of this approach, the challenges it faces, and the solutions that are being developed at UNSW Sydney.

Sex- and age-adjusted reference values for dynamic inspiratory constraints during incremental cycle ergometry.

Activity-related dyspnea in chronic lung disease is centrally related to dynamic (dyn) inspiratory constraints to tidal volume expansion. Lack of reference values for exertional inspiratory reserve (IR) has limited the yield of cardiopulmonary exercise testing in exposing the underpinnings of this disabling symptom. One hundred fifty apparently healthy subjects (82 males) aged 40-85 underwent incremental cycle ergometry. Based on exercise inspiratory capacity (ICdyn), we generated centile-based reference values for the following metrics of IR as a function of absolute ventilation: IRdyn1 ([1-(tidal volume/ICdyn)] x 100) and IRdyn2 ([1-(end-inspiratory lung volume/total lung capacity] x 100). IRdyn1 and IRdyn2 standards were typically lower in females and older subjects (p<0.05 for sex and age versus ventilation interactions). Low IRdyn1 and IRdyn2 significantly predicted the burden of exertional dyspnea in both sexes (p<0.01). Using these sex and age-adjusted limits of reference, the clinician can adequately judge the presence and severity of abnormally low inspiratory reserves in dyspneic subjects undergoing cardiopulmonary exercise testing.

Reference values for leg effort during incremental cycle ergometry in non-trained healthy men and women, aged 19-85.

Heightened sensation of leg effort contributes importantly to poor exercise tolerance in patient populations. We aim to provide a sex- and age-adjusted frame of reference to judge symptom's normalcy across progressively higher exercise intensities during incremental exercise. Two-hundred and seventy-five non-trained subjects (130 men) aged 19-85 prospectively underwent incremental cycle ergometry. After establishing centiles-based norms for Borg leg effort scores (0-10 category-ratio scale) versus work rate, exponential loss function identified the centile that best quantified the symptom's severity individually. Peak O2 uptake and work rate (% predicted) were used to threshold gradually higher symptom intensity categories. Leg effort-work rate increased as a function of age; women typically reported higher scores at a given age, particularly in the younger groups (p < 0.05). For instance, "heavy" (5) scores at the 95th centile were reported at ~200 W (<40 years) and ~90 W (≥70 years) in men versus ~130 W and ~70 W in women, respectively. The following categories of leg effort severity were associated with progressively lower exercise capacity: ≤50th ("mild"), >50th to <75th ("moderate"), ≥75th to <95th ("severe"), and ≥ 95th ("very severe") (p < 0.05). Although most subjects reporting peak scores <5 were in "mild" range, higher scores were not predictive of the other categories (p > 0.05). This novel frame of reference for 0-10 Borg leg effort, which considers its cumulative burden across increasingly higher exercise intensities, might prove valuable to judging symptom's normalcy, quantifying its severity, and assessing the effects of interventions in clinical populations.

Circulating pre-treatment T-cell receptor repertoire as a predictive biomarker in advanced or metastatic non-small-cell lung cancer patients treated with pembrolizumab alone or in combination with chemotherapy.

BACKGROUND: The circulating T-cell receptor (TCR) repertoire is a dynamic representation of overall immune responses in an individual. MATERIALS AND METHODS: We prospectively collected baseline blood from patients treated with first-line pembrolizumab monotherapy or in combination with chemotherapy. TCR repertoire metrics were correlated with clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS) and immune-related adverse events (irAEs). We built a logistic regression classifier by fitting all four TCR-ß repertoire metrics to the immune checkpoint inhibitor (ICI) CBR data. In the subsequent receiver operating characteristic (ROC) analysis of the resulting logistic regression model probabilities, the best cut-off value was selected to maximise sensitivity to predict CBR to ICI. RESULTS: We observed an association between reduced number of unique clones and CBR among patients treated with pembrolizumab monotherapy (cohort 1) [risk ratio = 2.86, 95% confidence interval (CI) 1.04-8.73, P = 0.039]. For patients treated with pembrolizumab plus chemotherapy (cohort 2), increased number of unique clones [hazard ratio (HR) = 2.96, 95% CI 1.28-6.88, P = 0.012] and Shannon diversity (HR = 2.73, 95% CI 1.08-6.87, P = 0.033), and reduced evenness (HR = 0.43, 95% CI 0.21-0.90, P = 0.025) and convergence (HR = 0.41, 95% CI 0.19-0.90, P = 0.027) were associated with improved PFS, while only an increased number of unique clones (HR = 4.62, 95% CI 1.52-14.02, P = 0.007) were associated with improved OS. Logistic regression models combining the TCR repertoire metrics improved the prediction of CBR (cohorts 1 and 2) and were strongly associated with PFS (cohort 1, HR = 0.38, 95% CI 0.19-0.78, P = 0.009) and OS (cohort 2, HR = 0.20, 95% CI 0.05-0.76, P < 0.0001). Reduced TCR conversion was associated with increased frequency of irAEs needing systemic steroid treatment. CONCLUSION: Combined pre-treatment circulating TCR metrics might serve as a predictive biomarker for clinical outcomes among patients with advanced non-small-cell lung cancer treated with pembrolizumab alone or in combination with chemotherapy.

Unraveling the Mysteries of Perineural Invasion in Benign and Malignant Conditions.

Perineural invasion (PNI) is defined as the dissemination of neoplastic cells within the perineural space. PNI can be a strong indicator of malignancy and is linked to poor prognosis and adverse outcomes in various malignant neoplasms; nevertheless, it can also be seen in benign pathologic conditions. In this review article, we discuss various signaling pathways and neurotrophic factors implicated in the development and progression of PNI. We also describe the methodology, benefits, and limitations of different in vitro, ex vivo, and in vivo models of PNI. The spectrum of presentation for PNI can range from diffuse spread within large nerves ("named" nerves) all the way through localized spread into unnamed microscopic nerves. Therefore, the clinical significance of PNI is related to its extent rather than its mere presence or absence. In this article, we discuss the guidelines for the identification and quantification of PNI in different malignant neoplasms based on the College of American Pathologists (CAP) and World Health Organization (WHO) recommendations. We also describe benign pathologic conditions and neoplasms demonstrating PNI and potential mimics of PNI. Finally, we explore avenues for the future development of targeted therapy options via modulation of signaling pathways involved in PNI.

An intellectual-disability-associated mutation of the transcriptional regulator NACC1 impairs glutamatergic neurotransmission.

Advances in genome sequencing technologies have favored the identification of rare de novo mutations linked to neurological disorders in humans. Recently, a de novo autosomal dominant mutation in NACC1 was identified (NM_052876.3: c.892C > T, NP_443108.1; p.Arg298Trp), associated with severe neurological symptoms including intellectual disability, microcephaly, and epilepsy. As NACC1 had never before been associated with neurological diseases, we investigated how this mutation might lead to altered brain function. We examined neurotransmission in autaptic glutamatergic mouse neurons expressing the murine homolog of the human mutant NACC1, i.e., Nacc1-R284W. We observed that expression of Nacc1-R284W impaired glutamatergic neurotransmission in a cell-autonomous manner, likely through a dominant negative mechanism. Furthermore, by screening for Nacc1 interaction targets in the brain, we identified SynGAP1, GluK2A, and several SUMO E3 ligases as novel Nacc1 interaction partners. At a biochemical level, Nacc1-R284W exhibited reduced binding to SynGAP1 and GluK2A, and also showed greatly increased SUMOylation. Ablating the SUMOylation of Nacc1-R284W partially restored its interaction with SynGAP1 but did not restore binding to GluK2A. Overall, these data indicate a role for Nacc1 in regulating glutamatergic neurotransmission, which is substantially impaired by the expression of a disease-associated Nacc1 mutant. This study provides the first functional insights into potential deficits in neuronal function in patients expressing the de novo mutant NACC1 protein.

A Meta-Analysis of Neurodevelopmental Outcomes following Intravitreal Bevacizumab for the Treatment of Retinopathy of Prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is the most common cause of preventable blindness in preterm infants. First-line treatments include intravitreal bevacizumab (IVB) or laser photocoagulation (LPC). OBJECTIVES: The aim of the study was to evaluate neurodevelopmental safety of IVB compared to LPC for ROP. METHODS: MEDLINE, Embase, and Cochrane library were searched up to September 2022. Studies were included with at least 12-month follow-up of primary outcomes such as severe neurodevelopmental impairment (sNDI), cerebral palsy (CP), and hearing impairment (HI). Secondary outcomes were moderate-to-severe neurodevelopmental impairment (msNDI), Bayley Scores of Infant Development (BSID-III), and visual impairment. RESULTS: 1,231 patients from 11 comparative studies were included. Quality of evidence was rated low for all outcomes. IVB was associated with a higher risk for sNDI (risk ratio [RR] = 1.25, 95% confidence interval [CI]: [1.01, 1.53], p = 0.04); and CP (RR = 1.40, CI: [1.08, 1.81], p = 0.01) compared to LPC. There was no significant difference between IVB and LPC for msNDI (RR = 1.15, CI: [0.98, 1.35], p = 0.08) and HI (RR = 1.43, CI: [0.86, 2.39], p = 0.17). BSID-III percentile scores were similar between IVB and LPC, with weighted mean differences of 1.51 [CI = -1.25, 4.27], 2.43 [CI = -1.36, 6.22], and 1.97 [CI = -1.06, 5.01] for cognitive, language, and motor domains, respectively (p > 0.05). CONCLUSION: To our knowledge, this is the largest meta-analysis on neurodevelopmental outcomes and the first to rigorously examine IVB monotherapy in ROP treatment. Compared to LPC, there was a marginally increased risk for sNDI and CP with IVB but little or no difference in the risk of msNDI and HI. Further randomized studies are needed to strengthen these findings.

Anti-diabetic effect of cotreatment with resveratrol and pioglitazone in diabetic rats.

OBJECTIVE: Limitations and side effects associated with current anti-diabetic treatments have necessitated the search for new therapeutic alternatives. This study aimed to explore the combined use of resveratrol (RVT) and established anti-diabetic drug pioglitazone (PGZ) against streptozotocin (STZ)-induced diabetes mellitus (DM). MATERIALS AND METHODS: STZ was supplemented daily to Sprague-Dawley rats to induce DM. The synergistic effect of the RVT (20 mg/kg) and PGZ (0.65 mg/kg) on DM complications was evaluated after 8 weeks of treatment. Biochemical analyses were performed to evaluate the effectiveness of our treatment on glucose level, insulin sensitivity, lipid disturbances, oxidative mediators and inflammatory markers. RESULTS: STZ induced DM onset that is accompanied with elevated diabetic markers, lipid disturbances, remarkable oxidative damage and hyper-inflammation. The PGZ+RVT combination has the best effect as illustrated by significant (p < 0.05) decreases in fasting blood glucose, insulin, HbA1c and HOMA-IR levels. This combination attenuated (p < 0.05) lipid disturbances and their associated elevated atherogenic biomarkers. At the same time, treatments with PGZ+RVT exhibited an anti-inflammatory effect as it attenuated the increase in inflammatory parameters (CRP, TNF-α, IL-6). Also, it restored total antioxidant capacity and peroxisome proliferator-activated receptor (PPARg) levels that decreased by STZ-DM induction. CONCLUSIONS: This study provides PGZ+RVT as promising DM therapeutic alternative. This synergistic combination alleviates most of DM-related complications and insulin resistance.

Novel ATM Gene c.5644 C > T (p.Arg1882*) Variant Detected in a Patient with Pancreatic Adenocarcinoma and Two Primary Non-Small Cell Lung Adenocarcinomas: A Case Report

Ataxia-telangiectasia is an autosomal recessive disorder that usually manifests in childhood due to mutations in the Ataxia-Telangiectasia Mutated (ATM) gene. It is believed that there is an association between this gene mutation/polymorphism and cancer risk, including breast, lung, and pancreatic cancers. We report a rare case of a 69-year-old woman who developed three different primary cancers, including non-small cell lung cancer (NSCLC) in both lungs and pancreatic adenocarcinoma, and was later found to have a rarely reported variant mutation in the ATM gene, namely Exon 39, c.5644 C > T. We hypothesize that the ATM gene, c.5644 C > T mutation could be a plausible contributor in the pathogenesis of these three cancers. This hypothesis has yet to be validated by larger studies that focus on a mechanistic approach involving DNA repair genes such as the ATM. More importantly, this paves the way to developing new patient-specific targeted therapies and inaugurating precision medicine as a cornerstone in cancer therapeutics.

Effect of Letrozole Administration as a Selective Aromatase Inhibitor on Male Rat's Reproductive Performance.

This study was designed to investigate the effect of administrating a selective aromatase inhibitor, letrozole, on the parameters of the rat's sperm and testicular histomorphology. A total of 40 male Wistar rats with an age of about 5 months old and an average weight of 190±10 g were divided randomly into 4 groups (n=10 each) and treated for 6 weeks. The first group (C) was given normal saline only as a control group. The second (T1), third (T2), and fourth (T3) groups received doses of 0.5, 1, and 1.5 mg/animal letrozole, respectively. At the end of the experiment (42 days), all animals were euthanized and the samples were obtained for more evolutions. The results of this study showed a significant increase in sperms quality (P-value≤0.05) while indicating a significant decrease in sperm abnormality in the T1 group, compared to the C group. Moreover, there was a significant difference represented by an increase in sperm quality, and a significant difference represented by a decrease in sperms abnormality in the T2 group, compared to the C group. On the other hand, there was a significant difference represented by an increase in sperm quality, and a significant difference represented by a decrease in sperm abnormality in the T3 group, compared to the T2 group. Normal somniferous tubules with high spermatoscopy counts were shown in histologic sections in the control group, primary and secondary spermatocytes with spermatozoa. In the T1 group, there was adequate spermatogenesis with a thick basement membrane. In the T2 group, there was normal testicular tissue with a significant increase in spermatogenic activity and number. In the T3 group, there was no significant atrophy or other pathology. The results of the current study suggested that letrozole improved spermatogenesis while causing no visible pathological alterations in testis tissue.

Macroscopic, histologic, and clinical assessment of acute graft-versus-host disease of the upper gastrointestinal tract within 6 weeks after allogeneic hematopoietic cell transplantation.

Acute graft-versus-host-disease (aGVHD) is the main cause of morbidity and nonrelapse mortality (NRM) following allogeneic hematopoietic cell transplantation (alloHCT). Nausea, vomiting, and anorexia after alloHCT can be early signs of aGVHD of the gastrointestinal tract (GIT) but may also reflect lasting mucosal damage or side effects of drugs. If upper GIT aGVHD is suspected, upper endoscopic evaluation and histological examination are crucial. Still, the interpretation of clinical symptoms, macroscopical alterations, and histological findings can be challenging. Therefore, we conducted a retrospective analysis on single-center data from 174 patients with suspected aGVHD of the upper GIT who underwent upper endoscopy within the first 6 weeks after alloHCT, to study the distribution of aGVHD-related histological findings in relation to clinical symptoms and macroscopic findings and to correlate the severity of changes with data on relapse and NRM. Our data suggest that biopsies of the duodenum reveal the severity of upper GIT aGVHD most accurately. While the histological grading correlated weakly with the severity of macroscopic changes, we found a tight correlation between histological and clinical grades of upper GIT aGVHD (p < 0.001). Although correlation of histological grading of upper GIT aGVHD with the risk for NRM missed statistical significance (HR 1.53, Lerner ≥1° versus <1º, p = 0.13), overall clinical aGVHD severity correlated with NRM (HR 4.3, IIIº-IVº versus 0-Iº, p < 0.01). In conclusion, biopsies from the duodenum are most sensitive in excluding aGVHD in patients with normal macroscopic findings at esophagogastroduodenoscopy. Clinical grading of aGVHD predicts NRM better than histological grading.

Association of Smoking with the Severity of H. pylori with the Extent of Its Impact on Blood Parameters.

H. pylori infection is considered a major global gastric disorder. Furthermore, the spread of H. pylori infection and its effect on systemic disorders and blood is not fully understood. On the other hand, the high percentage of smokers and their impacts on the health system have become a significant concern. Therefore, the current study aimed to compare the H. pylori infection in smokers and non-smokers and their effects on hematological parameters.190 patients participated and were divided into two groups; 95 were smokers and 95 were non-smokers. The Helicobacter pylori detector instrument showed that the participants were infected. Vein blood was collected to check hematological parameters via a fully automatic hematological analyzer (DIAGON Ltd.-D-Cell 60). The recorded data showed that the highest percentage of infected patients was 26-45 years in both smokers and non-smokers (P≤0.05). Furthermore, depending on the residence, our study revealed that the urban cases were the highest percentage compared to rural cases (P≤0.05). The hematological parameters showed that RBCs, Hb, PCV, MCV, MCH, and MCHC were significantly higher in smokers compared with non-smokers (P≤0.05).

Comparative Analysis of the Efficacies of the GeneXpert and Solid Culture Media Techniques in the Diagnosis of Mycobacterium Tuberculosis.

Tuberculosis is one of the predominant infectious diseases causing significant deaths worldwide. Detection of Mycobacterium tuberculosis bacilli (MTB) using culture media was officially recognized by World Health Organization. However, there is a significant limitation in the authenticity of evaluation for its effectiveness on clinically important attributes. GeneXpert detects the presence of Mycobacterium tuberculosis (M. tuberculosis) based on the detection of nucleic acid and is able to identify the resistance of both isoniazid (INH) and Rifampicin (RIF) drugs. In this technique, DNA amplification is done using the GeneXpert instrument in the suspected sample with a specific reagent cartridge. Although GeneXpert is a rapid technique compared to other diagnostic tools for MTB identification due to false-negative results, the culture media technique is still considered the gold standard in detecting M. tuberculosis. The current study was designed to evaluate the comparative efficacies of GeneXpert and the solid culture media technique in identifying MTB. Sputum samples of 250 (n=250) suspected tuberculosis (TB) patients were investigated using both diagnostic techniques. The results revealed that out of the 250 suspected patients, 30 (12%) samples were positive with the culture media technique, while only 17 (6.8%) samples showed positive results with GeneXpert. Culture tests and GeneXpert are not equally efficient in detecting M. tuberculosis. The current study's findings showed that the culture-based detection method for M. tuberculosis is more efficient and reliable than GeneXpert.

Multiple myeloma presenting as acute tubulointerstitial nephritis.

BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is a very rare paraneoplastic manifestation in patients with multiple myeloma (MM). It is an uncommon pattern of renal disease in such patients. CASE PRESENTATION: We report a case of an 82-year-old male who was admitted with acute kidney injury. Renal biopsy showed typical findings of light chain-associated ATIN with scattered inflammatory cells in the interstitium and associated active tubulitis. No other common manifestations of MM were present at the time of presentation, including hypercalcemia, hyperuricemia, proteinuria, bone pain or lytic bone lesions. Subsequent immunoassays revealed significant serum lambda light chain burden and Bence Jones protein in urine. Immunofluorescence demonstrated linear tubular basement membranes with positive staining for lambda light chain (3+). Electron microscopy (EM) further showed interstitial edema and inflammation. All the aforementioned findings are consistent with ATIN and supported the diagnosis of MM. CONCLUSIONS: In conclusion, light chain-associated ATIN should be considered in the differential diagnosis of acute interstitial nephritis. Henceforth, serum free light chains as well as serum and urine protein electrophoresis should be included in the workup of such patients.

Repurposing of Anticancer Stem Cell Drugs in Brain Tumors.

Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration-approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level.

A Second Wave for the Neurokinin Tac2 Pathway in Brain Research.

Despite promising advances in basic research of the neurokinin B/Tac2 pathway in both animals and humans, clinical applications are yet to be implemented. This is likely because of our limited understanding of the action of the pathway in the brain. While this system controls neuronal activity in multiple regions, the precise impact of Tac2-induced cellular responses on behavior remains unclear. Recently, elegant studies revealed a key contribution to stress-related behaviors and memory. Here, we discuss the crucial importance of bridging the gap between the Tac2 pathway's involvement in cell physiology and cognition to comprehend its role in health and disease. We propose that a better understanding of the Tac2 pathway in the brain could provide an essential perspective for basic investigations, which in turn will feed clinical research.

Immune signature of CCR7+ central memory T cells associates with disease severity and Immunoglobulin E in bronchial asthma.

Summary: Objective. CD4+T cell subtypes are the central orchestrators of airway inflammation in bronchialasthma (BA); however, the mechanisms that regulate their accumulation in asthmatic airways are still a challenging subject. In addition, neutrophils play a significant role in the development of airway remodeling and their presence may influence clinical presentation of BA being linked to the development of severe BA. Neutrophils have also been found to acquireantigen presenting functions, enabling them to directly activate T cells. The study aimed to evaluate the possible association of chemokine receptor 7 (CCR7)+ memory CD4+T cells andCCR4+ effector T cells with disease severity and immunoglobulin E (IgE) production as well as to explore the relationship between these cells and neutrophil function in both allergic andnon-allergic asthmatic patients. Methods. Flow cytometry was used to determine the expression of different T cell subset phenotypes (CCR7 memory CD4+ and CCR4+T cells using anti-human CD3, CD4, CD45RO, CCR4 and CCR7 monoclonal antibodies) utilizing peripheral blood mononuclear cells (PBMCs) isolated from 78 allergic asthmatic patients, 41 non-allergic asthmatic patients, and 40 healthy individuals. Moreover, neutrophils' phagocytic activity was assessed by ingestion of candida particles. Results. We demonstrated increased percentages of CCR7+ memory CD4+T cells and CCR4+CD4+T cells in patients compared to control, where this up regulation was significantly higher in allergic than non-allergic asthmatic patients. Additionally, these cells were negatively correlated with improved pulmonary tests and significantly associated with disease severity scores and IgE levels. The neutrophil phagocytic activity was markedly increased in patients compared to control, showing a significant positive correlation with disease severity. Conclusions. These findings suggest that increased CCR4+ CD4+ T cells and CCR7+ memory CD4+ T cells (Tcm) may be associated with BA severity, especially in allergic BA patients and can potentially contribute to the rational design of new therapeutic approaches for asthma in the future.

Impact of anatomy type of prostatic artery on the number of catheters needed for prostatic artery embolization.

PURPOSE: The purpose of this study was to assess the relationship between the number of microcatheters required for prostatic artery embolization (PAE) and the anatomy of the prostatic artery (PA). MATERIALS AND METHODS: All consecutive patients who underwent PAE between May 2017 and December 2018 were included. The anatomical description of the PAs was assessed by both global cone beam computed tomography and selective angiography and data on the resources used, in terms of microcatheters, were prospectively collected. RESULTS: A total of 215 consecutive patients (mean age, 66±8.7 [SD] years; range: 45-93 years), with a mean International Prostate Symptom Score of 21±7.4 (SD) and a mean prostate volume on magnetic resonance imaging of 88±38 (SD) mL (range: 30-200mL) underwent PAE. A single PA was observed in 347 hemipelvises (347/411; 84.4%) and double PAs in 64 (64/411; 15.6%). Eighty percent (173/215 patients) of PAEs were performed using a single microcatheter. Type I PA anatomy required significantly more microcatheters (1.15±0.39 [SD]; range: 1-3), than type II (1.04±0.19 [SD]; range: 1-2), type III (1.09±0.34 [SD]; range: 1-3) and type IV (1.06±0.27 [SD]; range: 1-2) (P=0.01 for all). CONCLUSION: PAE is feasible with limited per-intervention changes in devices for all types of PA anatomy encountered. This could help in the design of appropriate reimbursement policies in various healthcare settings.

Multiple myeloma presenting as acute tubulointerstitial nephritis

Background Acute tubulointerstitial nephritis (ATIN) is a very rare paraneoplastic manifestation in patients with multiple myeloma (MM). It is an uncommon pattern of renal disease in such patients. Case presentation We report a case of an 82-year-old male who was admitted with acute kidney injury. Renal biopsy showed typical findings of light chain-associated ATIN with scattered inflammatory cells in the interstitium and associated active tubulitis. No other common manifestations of MM were present at the time of presentation, including hypercalcemia, hyperuricemia, proteinuria, bone pain or lytic bone lesions. Subsequent immunoassays revealed significant serum lambda light chain burden and Bence Jones protein in urine. Immunofluorescence demonstrated linear tubular basement membranes with positive staining for lambda light chain (3+). Electron microscopy (EM) further showed interstitial edema and inflammation. All the aforementioned findings are consistent with ATIN and supported the diagnosis of MM. Conclusions In conclusion, light chain-associated ATIN should be considered in the differential diagnosis of acute interstitial nephritis. Henceforth, serum free light chains as well as serum and urine protein electrophoresis should be included in the workup of such patients.