Bimetallic Metal Sites in Metal-Organic Frameworks Facilitate the Production of 1-Butene from Electrosynthesized Ethylene.

Converting CO2 to synthetic hydrocarbon fuels is of increasing interest. In light of progress in electrified CO2 to ethylene, we explored routes to dimerize to 1-butene, an olefin that can serve as a building block to ethylene longer-chain alkanes. With goal of selective and active dimerization, we investigate a series of metal-organic frameworks having bimetallic catalytic sites. We find that the tunable pore structure enables optimization of selectivity and that periodic pore channels enhance activity. In a tandem system for the conversion of CO2 to 1-C4H8, wherein the outlet cathodic gas from a CO2-to-C2H4 electrolyzer is fed directly (via a dehumidification stage) into the C2H4 dimerizer, we study the highest-performing MOF found herein: M' = Ru and M″ = Ni in the bimetallic two-dimensional M'2(OAc)4M″(CN)4 MOF. We report a 1-C4H8 production rate of 1.3 mol gcat-1 h-1 and a C2H4 conversion of 97%. From these experimental data, we project an estimated cradle-to-gate carbon intensity of -2.1 kg-CO2e/kg-1-C4H8 when CO2 is supplied from direct air capture and when the required energy is supplied by electricity having the carbon intensity of wind.

Psychosocial Status and Self-Perception in Patients with Cleft Lip and/or Palate.

OBJECTIVE: To describe how the psychosocial status of patients with cleft lip and/or palate (CL/P) relates to patient-reported outcomes (PROs). DESIGN: Cross-sectional retrospective chart review. SETTING: Tertiary care pediatric hospital. PATIENTS/PARTICIPANTS: Patients aged 8 to 29 years attending cleft team evaluations during a 1-year period. MAIN OUTCOME MEASURES: CLEFT-Q. RESULTS: Patients (N = 158) with isolated or syndromic CL/P and mean age 13.4 ± 3.0 years were included. Fifteen (9%) patients had siblings who also had CL/P. Of 104 patients who met with the team psychologist, psychosocial concerns were identified in 49 (47%) patients, including 25 (24%) with Attention-Deficit/Hyperactivity Disorder or behavior concerns, 28 (27%) with anxiety, and 14 (13%) with depression or mood concerns. Younger age and having siblings with cleft were associated with better PROs, while psychosocial concerns were associated with worse PROs on Speech, Psychosocial, and Face Appearance scales. CONCLUSIONS: Patient perception of cleft outcomes is linked to psychosocial factors.

A Tailored COF for Visible-Light Photosynthesis of 2,3-Dihydrobenzofurans.

Heterogeneous photocatalysis is considered as an ecofriendly and sustainable approach for addressing energy and environmental persisting issues. Recently, heterogeneous photocatalysts based on covalent organic frameworks (COFs) have gained considerable attention due to their remarkable performance and recyclability in photocatalytic organic transformations, offering a prospective alternative to homogeneous photocatalysts based on precious metal/organic dyes. Herein, we report Hex-Aza-COF-3 as a metal-free, visible-light-activated, and reusable heterogeneous photocatalyst for the synthesis of 2,3-dihydrobenzofurans, as a pharmaceutically relevant structural motif, via the selective oxidative [3+2] cycloaddition of phenols with olefins. Moreover, we demonstrate the synthesis of natural products (±)-conocarpan and (±)-pterocarpin via the [3+2] cycloaddition reaction as an important step using Hex-Aza-COF-3 as a heterogeneous photocatalyst. Interestingly, the presence of phenazine and hexaazatriphenylene as rigid heterocyclic units in Hex-Aza-COF-3 strengthens the covalent linkages, enhances the absorption in the visible region, and narrows the energy band, leading to excellent activity, charge transport, stability, and recyclability in photocatalytic reactions, as evident from theoretical calculations and real-time information on ultrafast spectroscopic measurements.

Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

Long-Term Patient-Reported Outcomes in Internationally Adopted Children with Cleft Lip and Palate.

OBJECTIVE: To compare patient-reported outcomes (PROs) in internationally adopted patients with cleft lip and palate to those in non-adopted peers. DESIGN: Cross-sectional study. SETTING: Multidisciplinary cleft team at tertiary care hospital. PATIENTS: Patients aged ≥ 8 with cleft lip and palate attending routine cleft team evaluations September 2021 - September 2022. MAIN OUTCOME MEASURE: CLEFT-Q PRO scores. RESULTS: Sixty-four internationally adopted patients and 113 non-adopted patients with a mean age of 13 years were included. Compared to non-adopted peers, adopted patients demonstrated worse satisfaction with face appearance (mean 59 vs. 66, p = .044), speech function (mean 69 vs. 78, p = .005), and speech distress (mean 80 vs. 84, p = .032). No significant differences were observed on the nose, nostrils, teeth, lips, lip scar, jaws, psychological function, or social function scales (p > .05). Objective clinical evaluation corroborated these findings, with adopted patients demonstrating worse Pittsburgh Weighted Speech scores (mean 3.0 vs 1.9, p = .027) and greater incidence of articulation errors (64% vs 46%, p = .021). No significant differences were observed in rates of mood, anxiety, or behavior concerns identified on psychosocial assessment (p = .764). Among adopted patients, undergoing palatoplasty prior to adoption was associated with worse satisfaction with speech, appearance, school, and social function (p < .05). CONCLUSIONS: Patient-reported outcomes among internationally adopted adolescents and young adults with cleft lip and palate show slightly lower satisfaction with facial appearance and speech but otherwise demonstrate similar results to non-adopted peers on most appearance and psychosocial measures. PRO data correlated well with objective speech assessment and did not portend worse psychosocial function.

Hydropersulfides Inhibit Lipid Peroxidation and Protect Cells from Ferroptosis.

Hydropersulfides (RSSH) are believed to serve important roles in vivo, including as scavengers of damaging oxidants and electrophiles. The α-effect makes RSSH not only much better nucleophiles than thiols (RSH), but also much more potent H-atom transfer agents. Since HAT is the mechanism of action of the most potent small-molecule inhibitors of phospholipid peroxidation and associated ferroptotic cell death, we have investigated their reactivity in this context. Using the fluorescence-enabled inhibited autoxidation (FENIX) approach, we have found RSSH to be highly reactive toward phospholipid-derived peroxyl radicals (kinh = 2 × 105 M-1 s-1), equaling the most potent ferroptosis inhibitors identified to date. Related (poly)sulfide products resulting from the rapid self-reaction of RSSH under physiological conditions (e.g., disulfide, trisulfide, H2S) are essentially unreactive, but combinations from which RSSH can be produced in situ (i.e., polysulfides with H2S or thiols with H2S2) are effective. In situ generation of RSSH from designed precursors which release RSSH via intramolecular substitution or hydrolysis improve the radical-trapping efficiency of RSSH by minimizing deleterious self-reactions. A brief survey of structure-reactivity relationships enabled the design of new precursors that are more efficient. The reactivity of RSSH and their precursors translates from (phospho)lipid bilayers to cell culture (mouse embryonic fibroblasts), where they were found to inhibit ferroptosis induced by inactivation of glutathione peroxidase-4 (GPX4) or deletion of the gene encoding it. These results suggest that RSSH and the pathways responsible for their biosynthesis may act as a ferroptosis suppression system alongside the recently discovered FSP1/ubiquinone and GCH1/BH4/DHFR systems.

Metal-Organic Frameworks in Mixed-Matrix Membranes for High-Speed Visible-Light Communication.

Mixed-matrix membranes (MMMs) based on luminescent metal-organic frameworks (MOFs) and emissive polymers with the combination of their unique advantages have great potential in separation science, sensing, and light-harvesting applications. Here, we demonstrate MMMs for the field of high-speed visible-light communication (VLC) using a very efficient energy transfer strategy at the interface between a MOF and an emissive polymer. Our steady-state and ultrafast time-resolved experiments, supported by high-level density functional theory calculations, revealed that efficient and ultrafast energy transfer from the luminescent MOF to the luminescent polymer can be achieved. The resultant MMMs exhibited an excellent modulation bandwidth of around 80 MHz, which is higher than those of most well-established color-converting phosphors commonly used for optical wireless communication. Interestingly, we found that the efficient energy transfer further improved the light communication data rate from 132 Mb/s of the pure polymer to 215 Mb/s of MMMs. This finding not only showcases the promise of the MMMs for high-speed VLC but also highlights the importance of an efficient and ultrafast energy transfer strategy for the advancement of data rates of optical wireless communication.

Artificial intelligence in mammographic phenotyping of breast cancer risk: a narrative review.

BACKGROUND: Improved breast cancer risk assessment models are needed to enable personalized screening strategies that achieve better harm-to-benefit ratio based on earlier detection and better breast cancer outcomes than existing screening guidelines. Computational mammographic phenotypes have demonstrated a promising role in breast cancer risk prediction. With the recent exponential growth of computational efficiency, the artificial intelligence (AI) revolution, driven by the introduction of deep learning, has expanded the utility of imaging in predictive models. Consequently, AI-based imaging-derived data has led to some of the most promising tools for precision breast cancer screening. MAIN BODY: This review aims to synthesize the current state-of-the-art applications of AI in mammographic phenotyping of breast cancer risk. We discuss the fundamentals of AI and explore the computing advancements that have made AI-based image analysis essential in refining breast cancer risk assessment. Specifically, we discuss the use of data derived from digital mammography as well as digital breast tomosynthesis. Different aspects of breast cancer risk assessment are targeted including (a) robust and reproducible evaluations of breast density, a well-established breast cancer risk factor, (b) assessment of a woman's inherent breast cancer risk, and (c) identification of women who are likely to be diagnosed with breast cancers after a negative or routine screen due to masking or the rapid and aggressive growth of a tumor. Lastly, we discuss AI challenges unique to the computational analysis of mammographic imaging as well as future directions for this promising research field. CONCLUSIONS: We provide a useful reference for AI researchers investigating image-based breast cancer risk assessment while indicating key priorities and challenges that, if properly addressed, could accelerate the implementation of AI-assisted risk stratification to future refine and individualize breast cancer screening strategies.

Photochemical Release of Hydropersulfides.

Hydropersulfides (RSSH) have received significant interest in the field of redox biology because of their intriguing biochemical properties. However, because RSSH are inherently unstable, their study is challenging, and as a result, the details of their physiological roles remain ill-defined. Herein, we report strategies to release RSSH utilizing photoremovable protecting groups. RSSH protection with the well-established p-hydroxyphenacyl (pHP) photoprotecting group resulted in inefficient RSSH photorelease along with complex chemistry. Therefore, an alternative precursor was examined in which a self-immolative linker was inserted between the pHP group and RSSH, providing nearly quantitative RSSH release following photolysis at 365 nm. Inspired by these results, we also synthesized an analogous precursor derivatized with 7-diethylaminocoumarin (DEACM), a visible light-cleavable photoprotecting group. Photolysis of this precursor at 420 nm led to efficient RSSH release, and in vitro experiments demonstrated intracellular RSSH delivery in breast cancer MCF-7 cells.

High-Capacity NH4+ Charge Storage in Covalent Organic Frameworks.

Ammonium ions (NH4+), as non-metallic charge carriers, have spurred great research interest in the realm of aqueous batteries. Unfortunately, most inorganic host materials used in these batteries are still limited by the sluggish diffusion kinetics. Here, we report a unique hydrogen bond chemistry to employ covalent organic frameworks (COFs) for NH4+ ion storage, which achieves a high capacity of 220.4 mAh g-1 at a current density of 0.5 A g-1. Combining the theoretical simulation and materials analysis, a universal mechanism for the reaction of nitrogen and oxygen bridged by hydrogen bonds is revealed. In addition, we explain the solvation behavior of NH4+, leading to a relationship between redox potential and desolvation energy barrier. This work provides a new insight into NH4+ ion storage in host materials based on hydrogen bond chemistry. This mechanism can be leveraged to design and develop COFs for electrochemical energy storage.

Reaction of Nitroxyl (HNO) with Hydrogen Sulfide and Hydropersulfides.

Nitroxyl (HNO) has gained a considerable amount of attention because of its promising pharmacological effects. The biochemical mechanisms of HNO activity are associated with the modification of regulatory thiol proteins. Recently, several studies have suggested that hydropersulfides (RSSH), presumed signaling products of hydrogen sulfide (H2S)-mediated thiol (RSH) modification, are additional potential targets of HNO. However, the interaction of HNO with reactive sulfur species beyond thiols remains relatively unexplored. Herein, we present characterization of HNO reactivity with H2S and RSSH. The reaction of H2S with HNO leads to the formation of hydrogen polysulfides and sulfur (S8), suggesting a potential role in sulfane sulfur homeostasis. Furthermore, we show that hydropersulfides are more efficient traps for HNO than their thiol counterparts. The reaction of HNO with RSSH at varied stoichiometries has been examined with the observed production of various dialkylpolysulfides (RSSnSR) and other nitrogen-containing dialkylpolysulfide species (RSS-NH-SnR). We do not observe evidence of sulfenylsulfinamide (RS-S(O)-NH2) formation, a pathway expected by analogy with the known reactivity of HNO with thiol.

Routine third-trimester ultrasound for the detection of small-for-gestational age in low-risk pregnancies (ROTTUS study): randomized controlled trial.

OBJECTIVE: To compare the proportion of small-for-gestational-age (SGA) infants detected by routine third-trimester ultrasound vs those detected by selective ultrasound based on serial symphysis-fundus height (SFH) measurements (standard care) in low-risk pregnancy. METHODS: This was an open-label randomized controlled trial conducted at a hospital in Kenya between May 2018 and February 2020. Low-risk pregnant women were randomly allocated (ratio of 1:1) to routine ultrasound for fetal growth assessment between 36 + 0 and 37 + 6 weeks' gestation (intervention group) or to standard care, which involved a selective growth scan on clinical suspicion of fetal growth abnormality based on serial SFH measurements (control group). During ultrasound examination, fetal growth was assessed by measurement of the abdominal circumference (AC), and AC < 10th centile was used to diagnose a SGA fetus. The main prespecified outcomes were the detection of neonatal SGA, defined as birth weight < 10th centile, and of severe neonatal SGA, defined as birth weight < 3rd centile. The predictive performance of routine third-trimester ultrasound and selective ultrasound based on serial SFH measurements was determined using receiver-operating-characteristics (ROC)-curve analysis. RESULTS: Of 566 women assessed for eligibility, 508 (89.8%) were randomized, of whom 253 were allocated to the intervention group and 255 to the control group. Thirty-six babies in the intervention group and 26 in the control group had a birth weight < 10th centile. The detection rate of SGA infants by routine third-trimester ultrasound vs that by standard care was 52.8% (19/36) vs 7.7% (2/26) (P < 0.001) and the specificity was 95.5% (191/200) and 97.9% (191/195), respectively (P = 0.08). The detection rate of severe SGA was 66.7% (12/18) by routine ultrasound vs 8.3% (1/12) by selective ultrasound based on SFH measurements (P < 0.001), with specificities of 91.7% (200/218) and 98.1% (205/209), respectively (P = 0.006). The area under the ROC curve of routine third-trimester ultrasound in prediction of SGA was significantly greater than that of selective ultrasound based on SFH measurements (0.92 (95% CI, 0.87-0.96) vs 0.68 (95% CI, 0.58-0.77); P < 0.001). CONCLUSIONS: In low-risk pregnancy, routine ultrasound performed between 36 + 0 and 37 + 6 weeks is superior to selective ultrasound based on serial SFH measurements for the detection of true SGA, with high specificity. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Cover crops differentially influenced nitrogen and phosphorus loss in tile drainage and surface runoff from agricultural fields in Ohio, USA.

Nitrogen (N) and phosphorus (P) loss from crop production agriculture is transported to adjacent and downstream water bodies, resulting in negative environmental impacts including harmful and nuisance algal blooms. Cover crops are a conservation management practice that replaces bare soil with vegetation outside of the cash crop growing season, purportedly reducing N and P loss by increasing water and nutrient demand in agroecosystems. In this study, we compared nitrate (NO3--N), total N (TN), dissolved reactive P (DRP), and total P (TP) loads in subsurface (tile) drainage and surface runoff from fields with cover crop management (CC) and fields without cover crop management (NoCC) using continuous monitoring data from 40 agricultural fields located throughout northcentral Ohio, United States (US). We found that average monthly tile NO3--N and TN loads from CC fields were ~50% less than NoCC fields, while average monthly tile discharge, DRP, and TP loads did not differ between CC and NoCC fields. Cover crops also did not significantly influence average monthly surface metrics. Cover crops reduced monthly totals of tile NO3--N and TN loads by ~1.0-2.6 kg N ha-1 from January to June (winter and spring), coinciding with critical periods of nutrient loss from agroecosystems in the midwestern US, but increased monthly totals of tile DRP (by 0.4-12.1 g DRP ha-1) and TP (by 1.2-31.6 g TP ha-1) loads during some months. We found similar patterns at the annual time scale whereby CC fields had lesser cumulative annual totals of tile NO3--N and TN but greater cumulative annual totals of tile DRP and TP. These results show that the influence of cover crops on N loads, but not P, were consistent across temporal scales of examination, demonstrating that cover crops effectively increased N demand and mitigated N losses from agricultural fields. The variable influence of cover crops on P loads underscores the need for greater understanding of the factors and mechanisms that control P loss in systems that include cover crop management. Furthermore, these findings stress the importance of identifying and selecting conservation management practices tailored to the natural resource concern.

Plant Platforms for Efficient Heterologous Protein Production.

Production of recombinant proteins is primarily established in cultures of mammalian, insect and bacterial cells. Concurrently, concept of using plants to produce high-value pharmaceuticals such as vaccines, antibodies, and dietary proteins have received worldwide attention. Newer technologies for plant transformation such as plastid engineering, agroinfiltration, magnifection, and deconstructed viral vectors have been used to enhance the protein production in plants along with the inherent advantage of speed, scale, and cost of production in plant systems. Production of therapeutic proteins in plants has now a more pragmatic approach when several plant-produced vaccines and antibodies successfully completed Phase I clinical trials in humans and were further scheduled for regulatory approvals to manufacture clinical grade products on a large scale which are safe, efficacious, and meet the quality standards. The main thrust of this review is to summarize the data accumulated over the last two decades and recent development and achievements of the plant derived therapeutics. It also attempts to discuss different strategies employed to increase the production so as to make plants more competitive with the established production systems in this industry.

Raloxifene impedes cisplatin-induced nephrotoxicity through inhibition of Proinflammatory cytokines in female wistar rats.

Cisplatin mediated nephrotoxicity is the main obstacle in the practice of cisplatin as a chemotherapeutic agent. Conversely, it continues to be the most commonly used anticancer agent to treat several solid tumours. This study investigated the effect of raloxifene pretreatment on nephrotoxicity mediated by cisplatin in an experimental animal model. The levels of blood urea nitrogen, creatinine, and albumin were measured to evaluate the renal damage, and the levels of proinflammatory cytokines such as interleukin 6 (IL-6), interleukin 10 (IL-10), and tumour necrosis factor-alpha (TNF-α) were measured to assess the systemic inflammation. Cisplatin in a single dose of 7.5mg/kg showed a substantial rise in serum levels of blood urea nitrogen, creatinine along with TNF-α and IL-6 and, fall in albumin and IL-10 levels. Nevertheless, there was no substantial change in a group treated with raloxifene 7.5mg/kg. We observed a substantial fall in the levels of blood urea nitrogen, creatinine along with TNF-α and IL-6 and a rise in albumin and IL-10 levels. The current study established a protective effect of raloxifene in cisplatin mediated nephrotoxicity and this is due to its potential anti-oxidant and anti-inflammatory properties. Therefore, a cisplatin induced nephrotoxicity can be prevented by the use of raloxifene as a therapeutic adjuvant.

Alkylamine-Substituted Perthiocarbamates: Dual Precursors to Hydropersulfide and Carbonyl Sulfide with Cardioprotective Actions.

The recent discovery of hydropersulfides (RSSH) in mammalian systems suggests their potential roles in cell signaling. However, the exploration of RSSH biological significance is challenging due to their instability under physiological conditions. Herein, we report the preparation, RSSH-releasing properties, and cytoprotective nature of alkylamine-substituted perthiocarbamates. Triggered by a base-sensitive, self-immolative moiety, these precursors show efficient RSSH release and also demonstrate the ability to generate carbonyl sulfide (COS) in the presence of thiols. Using this dually reactive alkylamine-substituted perthiocarbamate platform, the generation of both RSSH and COS is tunable with respect to half-life, pH, and availability of thiols. Importantly, these precursors exhibit cytoprotective effects against hydrogen peroxide-mediated toxicity in H9c2 cells and cardioprotective effects against myocardial ischemic/reperfusion injury, indicating their potential application as new RSSH- and/or COS-releasing therapeutics.

The reactions of hydropersulfides (RSSH) with myoglobin.

Hydropersulfides are reported to be good biological reductants, superior to thiols and akin to selenols. As such, they have been previously shown to reduce metalloproteins such as ferric myoglobin and ferric cytochrome c to their ferrous forms under conditions where little or no reduction from corresponding thiols is observed. Not surprisingly, the reduction of ferric myoglobin to ferrous myoglobin under aerobic conditions results in the generation of oxymyoglobin (dioxygen bound ferrous myoglobin). Previous studies have demonstrated that oxymyoglobin can also act as an oxidant with highly reducing species such as hydroxylamine and ascorbate. Considering the reducing properties of hydropersulfides, it is possible that they can also react with oxymyoglobin similarly to hydroxylamine or ascorbate. Herein, this reaction is examined and indeed hydropersulfides are found to react with oxymyoglobin similarly to other reducing species leading to a fleeting ferric myoglobin which is rapidly reduced to the ferrous form also by hydropersulfide.

Impact of a multidisciplinary multimodal opioid minimization initiative in kidney transplant recipients.

Opioid use after kidney transplant has been shown to be a risk factor for chronic opioid use, which leads to an increased risk of mortality. The purpose of this study was to evaluate the early impact of a multimodal pain regimen and education quality improvement program on opioid use after kidney transplant 2 months after implementation. This was a retrospective, single-center analysis of post-operative opioid use, comparing the average daily Morphine milligram equivalents (MME) of the patients who received education on opioids and a multimodal pain regimen (preoperative TAP/QL block, scheduled APAP and gabapentin) compared to a historical control group. Despite having no differences in pre-transplant opioid exposure, daily and overall inpatient opioid utilization was significantly reduced in the multimodal pain protocol cohort (38.6 vs 8.0 MME/day; P < .001); 5% of patients in the multimodal pain protocol cohort were discharged with an opioid prescription, compared to 96% of controls (P < .001). Our early results demonstrate that a multimodal pain protocol can effectively and dramatically reduce short-term opioid utilization in kidney transplant recipients.

Renal allograft surveillance with allospecific T-cytotoxic memory cells.

BACKGROUND: Allo-antigen-specific T-cytotoxic memory cells (TcM) which express CD40 ligand (CD154) in overnight lymphocyte co-culture are strongly associated with acute cellular rejection (ACR) seen in "for cause" biopsies for renal allograft dysfunction. Specifically, when the likelihood of rejection is increased, donor-specific allospecific TcM exceed those induced by HLA-non-identical third-party cell by 1.15-fold or greater. METHODS: The performance of allospecific TcM was evaluated retrospectively in primary renal transplant recipients (RTR) at routine clinical visits, cross-sectionally at presentation for biopsies, and serially. Performance metrics were sensitivity, specificity, positive and negative predictive values (PPV and NPV). RESULTS: Twenty-two primary RTR, median age 45 years (range 19-72) were tested with allospecific CD154 + TcM. Samples were obtained at the mean ± SD time interval of 806 ± 239 days after kidney transplantation. Six of 22 patients experienced biopsy proven T- Cell Mediated Rejection (TCMR). A seventh showed antibody mediated rejection (ABMR). Of these seven patients six demonstrated increased likelihood of rejection with allospecific TcM (sensitivity 83%). Ten of these 15 patients with no rejection had a negative test (specificity 67%). False positive tests were seen in five patients. Six out of 11 patients with positive tests had ACR/ABMR with a PPV of 54%, while 10 out of 11 patients with negative tests were non-rejecters with a NPV of 91%. CONCLUSION: Allospecific T-cytotoxic memory cells distinguished primary RTR with quiescent allografts from those with dysfunction. With serial surveillance measures, this test system may facilitate decisions to manage immunosuppression in RTR.

Long-standing diabetes mellitus and pancreas transplantation: An avenue to increase utilization of an ideal treatment modality.

BACKGROUND: Diabetes mellitus (DM) is associated with increased post-operative complications in various surgeries. Little data exist regarding the impact of long-standing DM (>25 years) on outcomes in pancreas transplantation (PTX). The objectives of our study were to determine if long-standing pre-transplant DM (>25 years) was associated with inferior outcomes following PTX. METHODS: Using a 13-year (April, 2000-May, 2012) retrospective analysis, we examined demographic and transplant factors, complications, and outcomes in patients without (Group A) and with (Group B) long-standing (>25 years) pre-PTX DM. RESULTS: Mean follow-up was 4.2 years. Of 214 consecutive PTX performed, 137 (105 simultaneous PTX (SPK), 25 PTX after kidney (PAK), 7 PTX alone (PTA)) had pre-PTX duration of DM recorded, including 65 in Group A and 72 in Group B. There were no differences between cohorts with respect to demographics. There were no differences in post-PTX surgical/medical complications. There were no differences in outcomes between cohorts (ie, rejection, graft loss or death). CONCLUSIONS: This large-scale analysis demonstrated that PTX can be performed in patients with long-standing DM with excellent patient and graft outcomes. Long-standing DM did not lead to an increased post-PTX infections or complications. Our study suggests that duration of DM should not impact PTX candidacy.