Underlying and proximate drivers of biodiversity changes in Mesoamerican biosphere reserves.

Protected areas are of paramount relevance to conserving wildlife and ecosystem contributions to people. Yet, their conservation success is increasingly threatened by human activities including habitat loss, climate change, pollution, and species overexploitation. Thus, understanding the underlying and proximate drivers of anthropogenic threats is urgently needed to improve protected areas' effectiveness, especially in the biodiversity-rich tropics. We addressed this issue by analyzing expert-provided data on long-term biodiversity change (last three decades) over 14 biosphere reserves from the Mesoamerican Biodiversity Hotspot. Using multivariate analyses and structural equation modeling, we tested the influence of major socioeconomic drivers (demographic, economic, and political factors), spatial indicators of human activities (agriculture expansion and road extension), and forest landscape modifications (forest loss and isolation) as drivers of biodiversity change. We uncovered a significant proliferation of disturbance-tolerant guilds and the loss or decline of disturbance-sensitive guilds within reserves causing a "winner and loser" species replacement over time. Guild change was directly related to forest spatial changes promoted by the expansion of agriculture and roads within reserves. High human population density and low nonfarming occupation were identified as the main underlying drivers of biodiversity change. Our findings suggest that to mitigate anthropogenic threats to biodiversity within biosphere reserves, fostering human population well-being via sustainable, nonfarming livelihood opportunities around reserves is imperative.

Effectiveness and Safety of Atherectomy versus Plain Balloon Angioplasty for Limb Salvage in Tibioperoneal Arterial Disease.

PURPOSE: To evaluate the effectiveness and safety of atherectomy versus plain balloon angioplasty (POBA) for treatment of critical limb ischemia (CLI) due to tibioperoneal arterial disease (TPAD). MATERIALS AND METHODS: Patients enrolled in the Vascular Quality Initiative registry who had CLI (Rutherford Class 4-6) and underwent atherectomy versus POBA alone for isolated TPAD were retrospectively identified. Of eligible patients, a cohort of 2,908 patients was propensity matched 1:1 by clinical and angiographic characteristics. The atherectomy group comprised 1,454 patients with 2,183 arteries treated, and the POBA group comprised 1,454 patients with 2,141 arteries treated. The primary study endpoint was major ipsilateral limb amputation. Secondary endpoints were minor ipsilateral amputations, any ipsilateral amputation, primary patency, target vessel reintervention (TVR), and wound healing at 12 months. RESULTS: The median follow-up period was 507 days, the mean patient age was 69 years ± 11.7, and the mean occluded length was 6.9 cm ± 6.5. There was a trend toward higher technical success rates with atherectomy than with POBA (92.9% vs 91.0%, respectively; P = .06). The rates of major adverse events during the procedure were not significantly different. The 12-month major amputation rate was similar in the atherectomy and POBA groups (4.5% vs 4.6%, respectively; P = .92; odds ratio, 0.97; 95% CI, 0.68-1.37). There was no difference in 12-month TVR (17.9% vs 17.8%; P = .97) or primary patency (56.4% vs 54.5%; P = .64) between the atherectomy and POBA groups. CONCLUSIONS: In a large national registry, treatment of CLI from TPAD using atherectomy versus POBA showed no significant differences in procedural adverse events, major amputations, TVR, or vessel patency at 12 months.

The moderating role of everyday discrimination on the association between post-traumatic stress and loneliness among older Puerto Ricans.

OBJECTIVES: This study examines the relationship between post-traumatic stress and loneliness and whether this relationship varies by perceived everyday discrimination among older Puerto Ricans. METHODS: A total of 304 Puerto Ricans aged 60 and above from Wave 3 of the Boston Puerto Rican Health Study were included. Ordinary least squares regression examined the association between post-traumatic stress, perceived everyday discrimination, and loneliness. RESULTS: Post-traumatic stress was significantly associated with a higher level of loneliness (ß = 0.282; p < 0.001; 95% CI: 0.142, 0.423). The interaction effect between post-traumatic stress and perceived everyday discrimination on loneliness was statistically significant (ß = 0.083; p < 0.05; 95% CI: 0.062, 0.230). More specifically, the positive association between post-traumatic stress and loneliness becomes more robust with the increase in perceived everyday discrimination. CONCLUSION: Given an increase in population size on the U.S. mainland and migration from Puerto Rico due to natural disasters and declining economic conditions, it is essential to better understand the effect of perceived discrimination against older Puerto Ricans on the mainland United States as well as those who immigrated and stayed through older age. Outreach strategies and interventions that address perceived discrimination can help mitigate loneliness among older Puerto Ricans who experienced trauma.

Dysfunction of the circadian clock in the kidney tubule leads to enhanced kidney gluconeogenesis and exacerbated hyperglycemia in diabetes.

The circadian clock is a ubiquitous molecular time-keeping mechanism which synchronizes cellular, tissue, and systemic biological functions with 24-hour environmental cycles. Local circadian clocks drive cell type- and tissue-specific rhythms and their dysregulation has been implicated in pathogenesis and/or progression of a broad spectrum of diseases. However, the pathophysiological role of intrinsic circadian clocks in the kidney of diabetics remains unknown. To address this question, we induced type I diabetes with streptozotocin in mice devoid of the circadian transcriptional regulator BMAL1 in podocytes (cKOp mice) or in the kidney tubule (cKOt mice). There was no association between dysfunction of the circadian clock and the development of diabetic nephropathy in cKOp and cKOt mice with diabetes. However, cKOt mice with diabetes exhibited exacerbated hyperglycemia, increased fractional excretion of glucose in the urine, enhanced polyuria, and a more pronounced kidney hypertrophy compared to streptozotocin-treated control mice. mRNA and protein expression analyses revealed substantial enhancement of the gluconeogenic pathway in kidneys of cKOt mice with diabetes as compared to diabetic control mice. Transcriptomic analysis along with functional analysis of cKOt mice with diabetes identified changes in multiple mechanisms directly or indirectly affecting the gluconeogenic pathway. Thus, we demonstrate that dysfunction of the intrinsic kidney tubule circadian clock can aggravate diabetic hyperglycemia via enhancement of gluconeogenesis in the kidney proximal tubule and further highlight the importance of circadian behavior in patients with diabetes.

On-Demand Nanoliter Sampling Probe for the Collection of Brain Fluid.

Continuous fluidic sampling systems allow collection of brain biomarkers in vivo. Here, we propose a new sequential and intermittent sampling paradigm using droplets, called Droplet on Demand (DoD). It is implemented in a microfabricated neural probe and alternates phases of analyte removal from the tissue and phases of equilibration of the concentration in the tissue. It allows sampling droplets loaded with molecules from the brain extracellular fluid punctually, without the long transient equilibration periods typical of continuous methods. It uses an accurately defined fluidic sequence with controlled timings, volumes, and flow rates, and correct operation is verified by the embedded electrodes and a flow sensor. As a proof of concept, we demonstrated the application of this novel approach in vitro and in vivo, to collect glucose in the brain of mice, with a temporal resolution of 1-2 min and without transient regime. Absolute quantification of the glucose level in the samples was performed by direct infusion nanoelectrospray ionization Fourier transform mass spectrometry (nanoESI-FTMS). By adjusting the diffusion time and the perfusion volume of DoD, the fraction of molecules recovered in the samples can be tuned to mirror the tissue concentration at accurate points in time. Moreover, this makes quantification of biomarkers in the brain possible within acute experiments of only 20-120 min. DoD provides a complementary tool to continuous microdialysis and push-pull sampling probes. Thus, the advances allowed by DoD will benefit quantitative molecular studies in the brain, i.e., for molecules involved in volume transmission or for protein aggregates that form in neurodegenerative diseases over long periods.

Simultaneous mass spectrometry analysis of cisplatin with oligonucleotide-peptide mixtures: implications for the mechanism of action.

Although genomic DNA is the primary target of anticancer platinum-based drugs, interactions with proteins also play a significant role in their overall activity. In this study, competitive binding of cisplatin with an oligonucleotide and two peptides corresponding to segments of H2A and H2B histone proteins was investigated by mass spectrometry. Following the determination of the cisplatin binding sites on the oligonucleotide and peptides by tandem mass spectrometry, competitive binding was studied and transfer of platinum fragments from the platinated peptides to the oligonucleotide explored. In conjunction with previous studies on the nucleosome, the results suggest that all four of the abundant histone proteins serve as a platinum drug reservoir in the cell nucleus, providing an adduct pool that can be ultimately transferred to the DNA.

Comparison of partial least square, artificial neural network, and support vector regressions for real-time monitoring of CHO cell culture processes using in situ near-infrared spectroscopy.

The biopharmaceutical industry must guarantee the efficiency and biosafety of biological medicines, which are quite sensitive to cell culture process variability. Real-time monitoring procedures based on vibrational spectroscopy such as near-infrared (NIR) spectroscopy, are then emerging to support innovative strategies for retro-control of key parameters as substrates and by-product concentration. Whereas monitoring models are mainly constructed using partial least squares regression (PLSR), spectroscopic models based on artificial neural networks (ANNR) and support vector regression (SVR) are emerging with promising results. Unfortunately, analysis of their performance in cell culture monitoring has been limited. This study was then focused to assess their performance and suitability for the cell culture process challenges. PLSR had inferior values of the determination coefficient (R2 ) for all the monitored parameters (i.e., 0.85, 0.93, and 0.98, respectively for the PLSR, SVR, and ANNR models for glucose). In general, PLSR had a limited performance while models based on ANNR and SVR have been shown superior due to better management of inter-batch heterogeneity and enhanced specificity. Overall, the use of SVR and ANNR for the generation of calibration models enhanced the potential of NIR spectroscopy as a monitoring tool.

Performance Evaluation of the BD SARS-CoV-2 Reagents for the BD MAX System.

Nucleic acid amplification testing (NAAT) for SARS-CoV-2 is the standard approach for confirming COVID-19 cases. This study compared results between two emergency use authorization (EUA) NAATs, with two additional EUA NAATs utilized for discrepant testing. The limits of detection (LOD) for the BD SARS-CoV-2 reagents for the BD MAX system (MAX SARS-CoV-2 assay), the bioMérieux BioFire respiratory panel 2.1 (BioFire SARS-CoV-2 assay), the Roche cobas SARS-CoV-2 assay (cobas SARS-CoV-2 assay), and the Hologic Aptima SARS-CoV-2 assay Panther (Aptima SARS-CoV-2 assay) NAAT systems were determined using a total of 84 contrived nasopharyngeal specimens with 7 target levels for each comparator. The positive and negative percent agreement (PPA and NPA, respectively) of the MAX SARS-CoV-2 assay, compared to the Aptima SARS-CoV-2 assay, was evaluated in a postmarket clinical study utilizing 708 nasopharyngeal specimens collected from suspected COVID-19 cases. Discordant testing was achieved using the cobas and BioFire SARS-CoV-2 NAATs. In this study, the measured LOD for the MAX SARS-CoV-2 assay (251 copies/ml; 95% confidence interval [CI], 186 to 427) was comparable to the cobas SARS-CoV-2 assay (298 copies/ml; 95% CI, 225 to 509) and the BioFire SARS-CoV-2 assay (302 copies/ml; 95% CI, 219 to 565); the Aptima SARS-CoV-2 assay had an LOD of 612 copies/ml (95% CI, 474 to 918). The MAX SARS-CoV-2 assay had a PPA of 100% (95% CI, 97.3% to 100.0%) and an NPA of 96.7% (95% CI, 94.9% to 97.9%) compared to the Aptima SARS-CoV-2 assay. The clinical performance of the MAX SARS-CoV-2 assay agreed with another sensitive EUA assay.

Dry Powder Mixing Is Feasible in Continuous Twin Screw Extruder: Towards Lean Extrusion Process for Oral Solid Dosage Manufacturing.

Using discrete element method (DEM) modeling and near-infrared (NIR) spectroscopy, the feasibility of powder mixing in the initial pre-melting zones of a twin screw extruder using two independent feeders was studied. Previous work in the pharmaceutical and food industry has focused on mixing when materials are melted or on material homogeneity at the extruder's output. Depending on the formulation, ensuring a fully blended formulation prior to melting may be desired. Experiments were conducted using a Coperion ZSK-18 extruder to evaluate if blend uniformity can be achieved by exploring screw configuration, screw speed, and powder feed rate. As powder exited the extruder and deposited on a conveyor belt, an in-line NIR spectrophotometer measured spectra of material. Chemometric-based models predicted unknown concentrations to evaluate if blend uniformity was achieved. Using the EDEM software, Hertz-Mindlin contact model, and dimensions of the extruder, DEM simulations complemented the experimental work. The DEM computational models provided understanding of mixing patterns inside the extruder at particle scale and helped select the screw configuration before doing experimentation. The simulations showed good axial mixing for all the screw configurations studied, while good cross (radial) mixing was only observed for the screw configuration with 90-degree kneading elements. Therefore, the screw configuration with two 90-degree kneading elements was chosen for the experimental study. The RTD profiles when using a screw configuration with only conveying screw elements are comparable to a plug flow reactor (PFR), while the profiles when using kneading elements are more comparable to an ideal continuous stirred tank reactor (CSTR). For the screw configuration with 90 degrees kneading elements, the mean residence time (MRT) decreases with an increase in the screw speed. Experimental NIR spectra showed that concentrations can be predicted with an error of 2%. It was demonstrated that the twin screw extruder can provide proper dry powder mixing of two powder feed streams based on a unit dose scale, enabling continuous powder mixing prior to the melting zone in the extruder for the formulation studied with a cohesive API. This setup may also work for other types of formulations. These studies can help in developing lean hot melt as well as wet extrusion/granulation processes using twin screw extruders for the continuous manufacturing of oral solid dosage products.

The Traditional or Reverse Algorithm for Diagnosis of Syphilis: Pros and Cons.

We reviewed relevant syphilis diagnostic literature to address the question "What diagnostic considerations should be taken into account when screening for syphilis using the traditional or reverse algorithm?" Improved laboratory diagnosis of syphilis is an important element of the effort to reduce syphilis rates. Screening for syphilis is performed using either a nontreponemal or treponemal test (part of the traditional or reverse algorithm, respectively). Both syphilis algorithms are used by laboratories. However, there are limited data on the performance and cost-effectiveness of the algorithms. An expert panel generated "key questions" in the laboratory diagnosis of syphilis. This paper pertains to the key factors that should be considered when deciding whether to screen for syphilis using either the traditional or the reverse algorithm. A systematic literature review was performed, and tables of evidence were created to address this question.

Boronate Ester-Capped Helicates.

Triple-stranded helicates were obtained by metal-templated multicomponent reactions of bispyridyloxime ligands with arylboronic acids. The helicates feature two hexa-coordinated MII ions (M=Fe, Zn, or Mn), which are embedded in a macrobicyclic ligand framework, and two arylboronate ester capping groups. The latter can be used to introduce functional groups such as pyridines, aldehydes, nitriles, and carboxylic acids in apical position. The functionalized helicates have the potential to be used as nanoscale building blocks for more complex assemblies, as evidenced by the synthesis of a 3 nm-sized trianglimine.

Schistosoma haematobium infection modulates Plasmodium falciparum parasite density and antimalarial antibody responses.

AIMS: Schistosomiasis and malaria are endemic in sub-Saharan Africa where Schistosoma haematobium (Sh) and Plasmodium falciparum (Pf) coinfections are thus frequent. We explored the effect of Sh infection on antibody responses directed to Pf merozoite antigens and on malaria susceptibility in Beninese children. METHODS AND RESULTS: A total of 268 children were followed during a malaria transmission season. Detection of Pf infection was performed by microscopy and rapid diagnostic tests. Sh infection was determined in urine by microscopy. Antimalarial antibody, cytokine and HLA-G concentrations were quantified by ELISA. The expression of HLA-G receptors by immune cells was assessed by flow cytometry. Children infected by Sh had higher concentrations of IgG1 directed to MSP3 and GLURPR0 , IgG2 directed to GLURPR0 and IgG3 directed to MSP3, GLURPR0 and GLURPR2 and have lower Pf densities than those uninfected by Sh. No difference in cytokine and HLA-G concentrations was observed between Sh egg carriers and non-carriers. CONCLUSION: Schistosoma haematobium modulates host immune responses directed to Pf antigens. The absence of immune downregulation usually observed during helminth infections is surprising in our study. We hypothesize that the stage of Sh development could partly explain the immune pathways leading to increased antibody levels that favour better control of Pf parasitemia.

Aom2 S: A new web-based application for DNA/RNA tandem mass spectrometry data interpretation.

RATIONALE: The Analysis of Oligonucleotide Modifications from Mass Spectra (Aom2 S) was created to support the analysis of oligonucleotide mass spectra. This application complements the existing software tools by providing a comprehensive analysis of oligonucleotide fragments from high-resolution tandem mass spectrometry (HR-MS/MS) data in a flexible and user-friendly manner, directly accessible through a web browser without any need for installation. METHODS: MS measurements of aminoC6-DNA and inosine-RNA were performed using an LTQ Orbitrap FT-MS instrument. The obtained data were analyzed by our newly developed open-source package Aom2 S accessible from the ms.epfl.ch web page or directly at https://mstools.epfl.ch/am2s/ to demonstrate the various functionalities of this tool, notably the possibility to identify different product ions from a nucleotide sequence with any fixed/variable modification by matching theoretical isotopic patterns to any experimental mass spectra with similarity scores ranking. RESULTS: A detailed description of the Aom2 S tool with its user-friendly interface is exemplified using HR-MS/MS data of modified DNA and RNA oligonucleotides. Explanations of analysis parameters and tool workflow, as well as multiple options for viewing and exporting the results, are provided. Product ion assignment and modification localization can be achieved in seconds, and results can be exported as tables, matched mass spectra, and fragmentation maps. CONCLUSIONS: A new open source tool (Aom2 S) for the analysis of HR-MS/MS data for modified DNA and RNA oligonucleotides is described. Aom2 S is fast, highly flexible, and versatile, allowing automatic precursor and product ion assignment in a comprehensive manner, including internal fragments and variable modification localization, with clear graphical representation of the results.

In situ cell differentiation monitoring of Catharanthus roseus suspension culture processes by NIR spectroscopy.

Plant suspension culture is attracting interest as a promising platform to produce biological medicines due to the absence of virus, prions or DNA related to mammals during the production process. However, the heterogenic plant cell proliferation nature is particularly challenging for establishing industrial processes based on innovative approaches currently used, particularly in the animal cell culture industry. In this context, while Process Analytical Technology (PAT) tools have been used to monitor classical parameters such as biomass dry weight, its use in cells heterogeneity has received limited attention. Therefore, the feasibility of in situ monitoring of cell differentiation in plant cell suspensions employing NIR spectroscopy and chemometrics was investigated. Off-line measurements of cell heterogeneity in term of cell differentiation and in-line NIR spectra captured in 3 L bioreactor cultures were employed to generate calibration models. Then models were tested to estimate the population distribution of parenchyma, collenchyma and sclerenchyma cells during Catharanthus roseus suspension cultures. Results have proven in situ NIR spectroscopy as a capable PAT tool to monitor differentiated cells accurately and in real-time. These results are the starting point to follow-up PAT systems so that plant cell culture heterogeneity may be better understood and controlled in biopharmaceutical plant cell cultures.

Delineation of the Critical Parameters of Salt Catalysts in the N-Formylation of Amines with CO2.

N-formylation of amines combining CO2 as a C1 source with a hydrosilane reducing agent is a convenient route for the synthesis of N-formylated compounds. A large number of salts including ionic liquids (ILs) have been shown to efficiently catalyze the reaction and, yet, the key features of the catalyst remain unclear and the best salt catalysts for the reaction remain unknown. Here we demonstrate the detrimental effect of ion pairing on the catalytic activity and illustrate ways in which the strength of the interaction between the ions can be reduced to enhance interactions and, hence, reactivity with the substrates. In contrast to the current hypothesis, we also show that salt catalysts are more active as bases rather than nucleophiles and identify the pKa where the nucleophilic role of the catalyst switches to the more active basic role. The identification of these critical parameters allows the optimum salt catalyst and conditions for an N-formylation reaction to be predicted.

Histidine Targeting Heterobimetallic Ruthenium(II)-Gold(I) Complexes.

Inspired by the preferential, allosteric binding of RAPTA-T and auranofin to the nucleosome core particle , we describe the design and synthesis of a series of heterobimetallic ruthenium(II)-gold(I) complexes with varying spacer lengths ranging from four to eight polyethylene glycol units. Evaluation of their cytotoxicity reveals IC50 values in the low micromolar range against cisplatin sensitive and resistant human ovarian carcinoma (A2780, A2780cisR) and nontumoral human embryonic kidney (HEK293) cell lines. Binding studies monitored via mass spectrometry revealed an affinity for histidine residues on a fragment of the amyloid ß-protein (residues 1-16, employed as a model system), which is in accordance with the binding sites of parent drugs, RAPTA-C and auranofin, to the nucleosome core particle.

Pectobacterium carotovorum subsp. brasiliense Causes Soft Rot and Death of Neobuxbaumia tetetzo in Zapotitlan Salinas Valley, Puebla, Mexico.

Neobuxbaumia tetetzo (Coulter) Backeberg (tetecho) is a columnar cactus endemic to Mexico. Tetecho plants, flowers, fruits, and seeds play an important role in the semiarid ecosystem, as they serve as a refuge and food for insects, bats, and birds, and are widely used by ethnic groups since pre-Hispanic times. Tetecho is affected by a soft rot that damages the whole plant and causes its fall and disintegration. Eight bacterial colonies of similar morphology were isolated from plants showing soft rot and inoculated in healthy tetecho plants, reproducing typical symptoms of soft rot 9 days after inoculation. Ten representative isolates were selected for phenotypic and genetic identification using 16s rDNA, IGS 16S-23S rDNA, and rpoS genes and for pathogenicity tests on several members of the cactus family and other plants. Based on the results, these bacterial isolates were identified as Pectobacterium carotovorum subsp. brasiliense. Inoculation of this bacteria caused soft rot in different cacti, fruits, leaves, and roots of other plants. This is the first report of the subspecies brasiliense of P. carotovorum causing soft rot and death in cacti in the world and the first report of this subspecies in Mexico.

Antifibrotic Effect of Ketoprofen-Grafted Alginate Microcapsules in the Transplantation of Insulin Producing Cells.

The controlled release of small molecular modulators of the immune response from hydrogel microspheres (MS) used for cell immobilization is an attractive approach to reduce pericapsular fibrotic overgrowth (PFO) after transplantation. Ketoprofen is a well-known nonsteroidal anti-inflammatory drug involved in the early stage inflammation cascade. PEGylated derivatives of ketoprofen, presenting either ester or amide linkage to the drug, were synthesized and conjugated to the hydroxyl groups of sodium alginate (Na-alg). Functionalized cell-free and MIN6 cells containing MS were produced from the resulting modified alginates. In vitro quantification of ketoprofen release indicated regular and sustained drug delivery over 14 days, resulting from the hydrolytic cleavage of the ester bond. The release kinetics was enhanced over the initial 7 days by the presence of MIN6 cells, probably as a result of cell esterase activity. In the presence of amide bond, traces of ketoprofen were released over 14 days due to a much slower hydrolysis kinetics. Cell-free and MIN6 cells containing MS were transplanted in immune-competent mice, either in the peritoneal cavity or under the kidney capsule, with a follow-up period of 30 days. Comparison with nonmodified Ca-alg MS transplanted in the same conditions demonstrated a clear reduction in the severity of PFO for MS functionalized with ketoprofen. Quantification of collagen deposition on MIN6 cells containing MS transplanted under the kidney capsule revealed the significant effect of ketoprofen release to decrease fibrotic tissue formation. The impact was more pronounced when the drug was covalently conjugated by an ester linkage, allowing higher concentration of the anti-inflammatory compound to be delivered at the transplantation site. The functionality of microencapsulated MIN6 cells 30 days after transplantation was confirmed by detection of insulin positive cell content.

Pediatric patient with end-stage kidney disease secondary to Eagle-Barrett syndrome and metastatic unresectable hepatoblastoma treated successfully with chemotherapy and liver-kidney transplant.

HBL is the most common malignant liver neoplasm in children. The etiology of HBL is largely unknown but there are certain syndromes, such as Beckwith-Wiedemann syndrome, that have been clearly associated with an increased incidence of this malignancy. EBS, also known as prune belly syndrome, is a congenital anomaly characterized by lax abdominal musculature, bilateral cryptorchidism requiring, in some cases, hemodialysis due to significant kidney and urinary tract dysfunctions. Despite an improvement on the survival rates of patients with advanced-stage HBL, the presence of concomitant end-stage renal disease that occurs in patients with EBS constitutes a therapeutic challenge for the clinician not only due to the use of nephrotoxic chemotherapy but also due to the potential need for multi-organ transplant. We report case of a 2-year-old male patient with EBS diagnosed with stage IV, metastatic HBL successfully treated with multi-agent chemotherapy while on dialysis whom then underwent a simultaneous liver-kidney transplant followed by adjuvant chemotherapy. Ultimately, the patient achieved cancer remission with normalization of his renal function. Our report emphasizes that patients with HBL in the setting of EBS will not only require careful kidney function monitoring while receiving chemotherapy, but they might also need to undergo multi-organ transplantation in order to achieve adequate cancer control and also normalization of their kidney function. Awareness of this unusual association calls for further investigation to potentially establish a genetic association between these two disease processes.