Spatially resolved whole transcriptome profiling in human and mouse tissue using Digital Spatial Profiling.

Emerging spatial profiling technology has enabled high-plex molecular profiling in biological tissues, preserving the spatial and morphological context of gene expression. Here, we describe expanding the chemistry for the Digital Spatial Profiling platform to quantify whole transcriptomes in human and mouse tissues using a wide range of spatial profiling strategies and sample types. We designed multiplexed in situ hybridization probes targeting the protein-coding genes of the human and mouse transcriptomes, referred to as the human or mouse Whole Transcriptome Atlas (WTA). Human and mouse WTAs were validated in cell lines for concordance with orthogonal gene expression profiling methods in regions ranging from ∼10-500 cells. By benchmarking against bulk RNA-seq and fluorescence in situ hybridization, we show robust transcript detection down to ∼100 transcripts per region. To assess the performance of WTA across tissue and sample types, we applied WTA to biological questions in cancer, molecular pathology, and developmental biology. Spatial profiling with WTA detected expected gene expression differences between tumor and tumor microenvironment, identified disease-specific gene expression heterogeneity in histological structures of the human kidney, and comprehensively mapped transcriptional programs in anatomical substructures of nine organs in the developing mouse embryo. Digital Spatial Profiling technology with the WTA assays provides a flexible method for spatial whole transcriptome profiling applicable to diverse tissue types and biological contexts.

Hospital Addiction Medicine Consultation Service Orders and Outcomes by Patient Race and Ethnicity in an Urban, Safety-Net Hospital.

BACKGROUND: Hospital admissions involving substance use disorders are increasing and represent an opportunity to engage patients in substance use treatment. Addiction medicine consultation services improve access to medications for opioid use disorder (MOUD) and patient outcomes. However, as hospitals continue to adopt addiction medicine consultation services it is important to identify where disparities may emerge in the process of care. OBJECTIVE: To describe addiction medicine consultation service use by race and ethnicity as well as substance to identify opportunities to reduce substance use treatment disparities. DESIGN: Retrospective cohort study using 2016-2021 Electronic Health Record data from a large Midwest safety-net hospital. PARTICIPANTS: Hospitalized adults aged 18 or older, with one or more substance use disorders. MAIN MEASURES: Consultation orders placed, patient seen by consult provider, and receipt of MOUD by self-reported race. KEY RESULTS: Between 2016 and 2021, we identified 16,895 hospitalized patients with a substance use disorder. Consultation orders were placed for 6344 patients and 2789 were seen by the consult provider. Black patients were less likely (aOR = 0.58; 95% CI: 0.53-0.63) to have an addiction medicine consultation order placed and, among patients with a consultation order, were less likely (aOR = 0.74; 95% CI: 0.65-0.85) to be seen by the consult provider than White patients. Overall, Black patients with OUD were also less likely to receive MOUD in the hospital (aOR = 0.63; 95% CI: 0.50-0.79) compared to White patients. However, there were no differences in MOUD receipt among Black and White patients seen by the consult provider. CONCLUSIONS: Using Electronic Health Record data, we identified racial and ethnic disparities at multiple points in the inpatient addiction medicine consultation process. Addressing these disparities may support more equitable access to MOUD and other substance use treatment in the hospital setting.

Patient Heterogeneity and the J-Curve Relationship Between Time-to-Antibiotics and the Outcomes of Patients Admitted With Bacterial Infection.

OBJECTIVES: Sepsis remains a leading and preventable cause of hospital utilization and mortality in the United States. Despite updated guidelines, the optimal definition of sepsis as well as optimal timing of bundled treatment remain uncertain. Identifying patients with infection who benefit from early treatment is a necessary step for tailored interventions. In this study, we aimed to illustrate clinical predictors of time-to-antibiotics among patients with severe bacterial infection and model the effect of delay on risk-adjusted outcomes across different sepsis definitions. DESIGN: A multicenter retrospective observational study. SETTING: A seven-hospital network including academic tertiary care center. PATIENTS: Eighteen thousand three hundred fifteen patients admitted with severe bacterial illness with or without sepsis by either acute organ dysfunction (AOD) or systemic inflammatory response syndrome positivity. MEASUREMENTS AND MAIN RESULTS: The primary exposure was time to antibiotics. We identified patient predictors of time-to-antibiotics including demographics, chronic diagnoses, vitals, and laboratory results and determined the impact of delay on a composite of inhospital death or length of stay over 10 days. Distribution of time-to-antibiotics was similar across patients with and without sepsis. For all patients, a J-curve relationship between time-to-antibiotics and outcomes was observed, primarily driven by length of stay among patients without AOD. Patient characteristics provided good to excellent prediction of time-to-antibiotics irrespective of the presence of sepsis. Reduced time-to-antibiotics was associated with improved outcomes for all time points beyond 2.5 hours from presentation across sepsis definitions. CONCLUSIONS: Antibiotic timing is a function of patient factors regardless of sepsis criteria. Similarly, we show that early administration of antibiotics is associated with improved outcomes in all patients with severe bacterial illness. Our findings suggest identifying infection is a rate-limiting and actionable step that can improve outcomes in septic and nonseptic patients.

Super fragmented: a nationally representative cross-sectional study exploring the fragmentation of inpatient care among super-utilizers.

BACKGROUND: Super-utilizers with 4 or more admissions per year frequently receive low-quality care and disproportionately contribute to healthcare costs. Inpatient care fragmentation (admission to multiple different hospitals) in this population has not been well described. OBJECTIVE: To determine the prevalence of super-utilizers who receive fragmented care across different hospitals and to describe associated risks, costs, and health outcomes. RESEARCH DESIGN: We analyzed inpatient data from the Health Care Utilization Project's State Inpatient and Emergency Department database from 6 states from 2013. After identifying hospital super-utilizers, we stratified by the number of different hospitals visited in a 1-year period. We determined how patient demographics, costs, and outcomes varied by degree of fragmentation. We then examined how fragmentation would influence a hospital's ability to identify super-utilizers. SUBJECTS: Adult patients with 4 or more inpatient stays in 1 year. MEASURES: Patient demographics, cost, 1-year hospital reported mortality, and probability that a single hospital could correctly identify a patient as a super-utilizer. RESULTS: Of the 167,515 hospital super-utilizers, 97,404 (58.1%) visited more than 1 hospital in a 1-year period. Fragmentation was more likely among younger, non-white, low-income, under-insured patients, in population-dense areas. Patients with fragmentation were more likely to be admitted for chronic disease management, psychiatric illness, and substance abuse. Inpatient fragmentation was associated with higher yearly costs and lower likelihood of being identified as a super-utilizer. CONCLUSIONS: Inpatient care fragmentation is common among super-utilizers, disproportionately affects vulnerable populations. It is associated with high yearly costs and a decreased probability of correctly identifying super-utilizers.

Bilateral enucleation in dogs: A review of owner perceptions and satisfaction.

PURPOSE: To evaluate owner perceptions of the quality of life of their dogs before and after bilateral enucleation and to assess owner satisfaction with the procedure. METHODS: Medical records of 72 dogs from the Willows Veterinary Centre and Referral Service (49 dogs) and the Royal Veterinary College (RVC, 23 dogs) that had undergone bilateral enucleation, either in one procedure or at different times, between April 2008 (Willows) or 2012 (RVC) and April 2017, were reviewed. Owners were initially telephoned to determine owner satisfaction, followed by a postal visual analogue scale (VAS) questionnaire evaluating perceptions of their dog's quality of life before and after the bilateral enucleation. Statistical evaluation included Wilcoxon signed-rank tests and Chi-squared analysis. RESULTS: Of the 72 cases identified, 63 owners (88%) were contacted by telephone and 60 owners (83%) also completed the VAS questionnaire. The mean age at the time of the second or bilateral enucleation was 8.47 years (range 7.1 months-14.5 years). Cross-breeds (n = 12, 17%) and Jack Russell Terriers (n = 7, 10%) were the two most represented breeds. Glaucoma was the most common reason for enucleation (139/144 eyes, 97%). Most owners (57/63, 90%) were satisfied with the surgery and would consent to the procedure again. Statistically significant improvements in owner perceptions of their dog's pain level, reaction to facial/ocular palpation, activity levels, and quality of life were identified post-enucleation. CONCLUSIONS: Following bilateral enucleation, owners were satisfied with the procedure and perceived their dogs to have a good quality of life.

Ocular biometry by computed tomography in different dog breeds.

OBJECTIVE: To (i) correlate B-mode ocular ultrasound (US) and computed tomography (CT) (prospective pilot study), (ii) establish a reliable method to measure the normal canine eye using CT, (iii) establish a reference guide for some dog breeds, (iv) compare eye size between different breeds and breed groups, and (v) investigate the correlation between eye dimensions and body weight, gender, and skull type (retrospective study). PROCEDURE: B-mode US and CT were performed on ten sheep cadaveric eyes. CT biometry involved 100 adult pure-bred dogs with nonocular and nonorbital disease, representing eleven breeds. Eye length, width, and height were each measured in two of three planes (horizontal, sagittal, and equatorial). RESULTS: B-mode US and CT measurements of sheep cadaveric eyes correlated well (0.70-0.71). The shape of the canine eye was found to be akin to an oblate spheroid (a flattened sphere). A reference guide was established for eleven breeds. Eyes of large breed dogs were significantly larger than those of medium and small breed dogs (P < 0.01), and eyes of medium breed dogs were significantly larger than those of small breed dogs (P < 0.01). Eye size correlated with body weight (0.74-0.82) but not gender or skull type. CONCLUSIONS: Computed tomography is a suitable method for biometry of the canine eye, and a reference guide was established for eleven breeds. Eye size correlated with breed size and body weight. Because correlation between B-mode US and CT was shown, the obtained values can be applied in the clinical setting, for example, for the diagnosis of microphthalmos and buphthalmos.

Outcome of phacoemulsification following corneal and lens laceration in cats and dogs (2000-2010).

OBJECTIVE: To investigate the success rate of phacoemulsification following corneal and lens laceration in dogs and cats. PROCEDURE: Retrospective review of cats and dogs presenting with corneal and lens laceration and treated with phacoemulsification. RESULTS: The records of 33 patients (33 eyes: six feline, 27 canine) presenting to a private referral center were reviewed. Affected dogs were younger (median 18 months) than affected cats (median 30 months). The lacerations were caused by cat scratch trauma (9/33), thorn injury (6/33), and glass shards (1/33); the cause was unknown in 17/33 cases. All cats and 85.2% of all dogs were visual at the last examination. The median follow-up was 4 and 8 months for cats and dogs, respectively. In all canine cases that developed vision loss, this occurred within the first 14 weeks postoperatively. The ultimate cause for vision loss in dogs was secondary glaucoma (4/4) and retinal detachment (1/4). CONCLUSION: Cats have an excellent outcome and dogs a very good outcome following surgery for corneal and lens laceration. The cause of the trauma, the size of the lesion, the time interval between the ocular trauma and surgery, and the type of surgery were not found to have an influence on the outcome of patients in this study. We postulate that vision loss might develop more often in cases with complications associated with the initial corneal laceration wound.

A small-cell lung cancer genome with complex signatures of tobacco exposure.

Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in frame, and another two lines carrying PVT1-CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.

Diagnosis and management of acute appendicitis. EAES consensus development conference 2015.

Unequivocal international guidelines regarding the diagnosis and management of patients with acute appendicitis are lacking. The aim of the consensus meeting 2015 of the EAES was to generate a European guideline based on best available evidence and expert opinions of a panel of EAES members. After a systematic review of the literature by an international group of surgical research fellows, an expert panel with extensive clinical experience in the management of appendicitis discussed statements and recommendations. Statements and recommendations with more than 70 % agreement by the experts were selected for a web survey and the consensus meeting of the EAES in Bucharest in June 2015. EAES members and attendees at the EAES meeting in Bucharest could vote on these statements and recommendations. In the case of more than 70 % agreement, the statement or recommendation was defined as supported by the scientific community. Results from both the web survey and the consensus meeting in Bucharest are presented as percentages. In total, 46 statements and recommendations were selected for the web survey and consensus meeting. More than 232 members and attendees voted on them. In 41 of 46 statements and recommendations, more than 70 % agreement was reached. All 46 statements and recommendations are presented in this paper. They comprise topics regarding the diagnostic work-up, treatment indications, procedural aspects and post-operative care. The consensus meeting produced 46 statements and recommendations on the diagnostic work-up and management of appendicitis. The majority of the EAES members supported these statements. These consensus proceedings provide additional guidance to surgeons and surgical residents providing care to patients with appendicitis.

European Association of Endoscopic Surgeons (EAES) consensus statement on the use of robotics in general surgery.

Following an extensive literature search and a consensus conference with subject matter experts the following conclusions can be drawn: 1. Robotic surgery is still at its infancy, and there is a great potential in sophisticated electromechanical systems to perform complex surgical tasks when these systems evolve. 2. To date, in the vast majority of clinical settings, there is little or no advantage in using robotic systems in general surgery in terms of clinical outcome. Dedicated parameters should be addressed, and high quality research should focus on quality of care instead of routine parameters, where a clear advantage is not to be expected. 3. Preliminary data demonstrates that robotic system have a clinical benefit in performing complex procedures in confined spaces, especially in those that are located in unfavorable anatomical locations. 4. There is a severe lack of high quality data on robotic surgery, and there is a great need for rigorously controlled, unbiased clinical trials. These trials should be urged to address the cost-effectiveness issues as well. 5. Specific areas of research should include complex hepatobiliary surgery, surgery for gastric and esophageal cancer, revisional surgery in bariatric and upper GI surgery, surgery for large adrenal masses, and rectal surgery. All these fields show some potential for a true benefit of using current robotic systems. 6. Robotic surgery requires a specific set of skills, and needs to be trained using a dedicated, structured training program that addresses the specific knowledge, safety issues and skills essential to perform this type of surgery safely and with good outcomes. It is the responsibility of the corresponding professional organizations, not the industry, to define the training and credentialing of robotic basic skills and specific procedures. 7. Due to the special economic environment in which robotic surgery is currently employed special care should be taken in the decision making process when deciding on the purchase, use and training of robotic systems in general surgery. 8. Professional organizations in the sub-specialties of general surgery should review these statements and issue detailed, specialty-specific guidelines on the use of specific robotic surgery procedures in addition to outlining the advanced robotic surgery training required to safely perform such procedures.

Minimally invasive oesophagectomy versus open surgery: is there an advantage?

BACKGROUND: Oesophageal resection is the main method of curative treatment for cancer of the oesophagus. Despite advances in surgical technology and postoperative care, the survival rate and prognosis of people undergoing oesophagectomy is still poor. The use of minimally invasive techniques in oesophageal surgery offers hope of reduced recovery time due to a reduction in surgical trauma. Although the first reports of thoracoscopy- and laparoscopy-assisted oesophagectomy emerged some 20 years ago, there is still no consensus that the outcomes are clearly superior to outcomes following conventional open surgery. Increasingly, some surgeons promote the use of minimally invasive techniques for oesophagectomy but questions remain over its safety and efficacy compared with open surgery. METHODS: We conducted a systematic review of the literature to compare minimally invasive techniques for oesophagectomy to open surgery. The outcomes of interest for efficacy and safety included mortality, operative complications, recurrence, and quality of life. RESULTS: There were 28 included comparative studies. No randomised controlled studies (RCTs) were available and therefore the data need to be interpreted with caution. CONCLUSION: Recommendations for future research are discussed. We argue that it is difficult to conduct an RCT for this procedure due to ethical considerations and suggest ways that future nonrandomised studies could be improved.

Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding.

We describe the genome sequencing of an anonymous individual of African origin using a novel ligation-based sequencing assay that enables a unique form of error correction that improves the raw accuracy of the aligned reads to >99.9%, allowing us to accurately call SNPs with as few as two reads per allele. We collected several billion mate-paired reads yielding approximately 18x haploid coverage of aligned sequence and close to 300x clone coverage. Over 98% of the reference genome is covered with at least one uniquely placed read, and 99.65% is spanned by at least one uniquely placed mate-paired clone. We identify over 3.8 million SNPs, 19% of which are novel. Mate-paired data are used to physically resolve haplotype phases of nearly two-thirds of the genotypes obtained and produce phased segments of up to 215 kb. We detect 226,529 intra-read indels, 5590 indels between mate-paired reads, 91 inversions, and four gene fusions. We use a novel approach for detecting indels between mate-paired reads that are smaller than the standard deviation of the insert size of the library and discover deletions in common with those detected with our intra-read approach. Dozens of mutations previously described in OMIM and hundreds of nonsynonymous single-nucleotide and structural variants in genes previously implicated in disease are identified in this individual. There is more genetic variation in the human genome still to be uncovered, and we provide guidance for future surveys in populations and cancer biopsies.

Cataracts are not associated with retinal detachment in the Bichon Frise in the UK--a retrospective study of preoperative findings and outcomes in 40 eyes.

OBJECTIVE: The aim of this study was to evaluate whether the Bichon Frise population in the UK is at the same risk of developing retinal detachment in association with cataract formation and following phacoemulsification as described in reports from the USA. PROCEDURES: The medical records of Bichon Frises which were presented for cataract assessment and of those which were treated with phacoemulsification at Willows Referral Service between 1997 and 2009 were reviewed. RESULTS: Forty eyes (26 dogs) with unilateral or bilateral cataracts were included in the study. There was no evidence of retinal detachment associated with the cataracts at initial presentation. Phacoemulsification was performed on 34 eyes (20 dogs). Clinically evident lens-induced uveitis was treated preoperatively in 17/34 eyes. Artificial lens implantation was carried out in 30/34 eyes; automated anterior vitrectomy was performed in 7/34 eyes. The mean follow-up time was 16.6 months (range 1.5-73 months). At the last re-examination, 31/34 eyes (91.2%) were visual. Three eyes (8.8%) were blind--two (in the same dog) because of presumptive bilateral optic nerve disease and one because of uveitis and secondary glaucoma. There was no evidence of retinal detachment following phacoemulsification in any of the 34 eyes. CONCLUSION: This study suggests that the Bichon Frise population in the UK does not appear to have a predisposition for retinal detachment in association with cataract formation or following cataract surgery. Prophylactic random transscleral laser retinopexy or transscleral cryopexy cannot therefore be routinely recommended for Bichon Frises with cataracts in the UK.

Deadly dozen: dealing with the 12 types of thoracic injuries.

Although most thoracic trauma may be treated non-operatively, major thoracic trauma accounts for 25% of trauma deaths. Except for provision of a definitive airway and/or relief of a tension pneumothorax with a needle decompression, the vast majority of thoracic trauma is best served with "load and go," high-flow oxygen, placement of an IV line and administration of crystalloid solutions as the clinical scenario would indicate. Understanding the mechanism of injury is helpful in establishing both prehospital and in-hospital management priorities. Patients who sustain a single penetrating wound to the chest have the best survivability after a resuscitative thoracotomy. Practicing chest assessment skills is vital to being a good prehospital provider. Ultrasound, NIRS tissue oxygenation and telemedicine will likely become more commonly employed as prehospital monitoring options. PEEP, or "over bagging," may exacerbate a simple or open pneumothorax, converting it to a tension pneumothorax.

An Atypical Case of Extrapulmonary Sarcoidosis.

Sarcoidosis is an idiopathic, inflammatory condition that affects nearly all organs in the body. Lungs are the most frequent and among the earliest sites for detecting it. The most common extrapulmonary manifestations involve the ophthalmic, cardiac, nervous, reticuloendothelial, cutaneous, hepatosplenic, and renal systems. These extrapulmonary manifestations of sarcoid may be misdiagnosed in the absence of the classical pulmonary features, given the high overlap of features with other chronic immunologic diseases. The diagnostic workup to differentiate sarcoid from other similar conditions is extensive, amongst which histology remains a gold standard tool for the diagnosis. Our patient presented with a chronic history of multiple vague complaints including nausea, vomiting, progressive malaise, vision changes, and weight loss. After extensive workup, a diagnosis of sarcoidosis along with multiple rare extrapulmonary involvements was made. The authors highlight essential implications including primary practice goals to avoid misdiagnosis or missed sarcoid diagnoses thus helping improve clinical outcomes in similar populations.

High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging.

Resolving the spatial distribution of RNA and protein in tissues at subcellular resolution is a challenge in the field of spatial biology. We describe spatial molecular imaging, a system that measures RNAs and proteins in intact biological samples at subcellular resolution by performing multiple cycles of nucleic acid hybridization of fluorescent molecular barcodes. We demonstrate that spatial molecular imaging has high sensitivity (one or two copies per cell) and very low error rate (0.0092 false calls per cell) and background (~0.04 counts per cell). The imaging system generates three-dimensional, super-resolution localization of analytes at ~2 million cells per sample. Cell segmentation is morphology based using antibodies, compatible with formalin-fixed, paraffin-embedded samples. We measured multiomic data (980 RNAs and 108 proteins) at subcellular resolution in formalin-fixed, paraffin-embedded tissues (nonsmall cell lung and breast cancer) and identified >18 distinct cell types, ten unique tumor microenvironments and 100 pairwise ligand-receptor interactions. Data on >800,000 single cells and ~260 million transcripts can be accessed at http://nanostring.com/CosMx-dataset .

Assessment of cosmetic outcome after laparoscopic cholecystectomy among women 4 years after laparoscopic cholecystectomy: is there a problem?

BACKGROUND: Advocates of single-port laparoscopic cholecystectomy (SPLC) claim that improved cosmetic outcome is one of its main benefits over conventional laparoscopic cholecystectomy (CLC). However, the published data quantifying the cosmetic outcome after CLC is sparse. This study aimed to determine the cosmetic outcome after CLC using a validated scar assessment tool. METHODS: The patient scar assessment questionnaire was sent to all women ages 20-50 years who had undergone CLC at the Norfolk and Norwich University Hospital (Norwich), the Homerton Hospital (London), and the Musgrove Park Hospital (Taunton) in 2005 (n = 380). In all cases, the operation had been performed using a four-port technique. The patients were asked to give scores related to the appearance and symptoms associated with the scars at the time the questionnaire was completed. RESULTS: Of the 380 patients, 195 responded to the questionnaire, giving a response rate of 51%. The median age of the responders was 39 years, and 63 (32%) of them had undergone previous surgery. The mean score for each section was low, indicating a favorable cosmetic outcome. This correlated with the global question answered with "excellent" for 4 of 5 categories and "good" for the remaining category. Nine patients highlighted dissatisfaction with the umbilical incision. CONCLUSIONS: Patients perceive the cosmetic results after CLC as excellent. Therefore, SPLC seems to have a limited role in terms of improving cosmesis for patients undergoing cholecystectomy. Anecdotal evidence from the questionnaire suggests that the umbilical port may be the site of problems for some patients. Further investigation is needed to determine whether this is significant, especially because it may be exaggerated after SPLC.

Hyperammonemia in the setting of Roux-en-Y gastric bypass presenting with osmotic demyelination syndrome.

Hyperammonemia can lead to serious outcomes including brain herniation, coma and death. It is often attributed to liver disease, specifically in association with alcohol use. However, in the absence of liver pathology, it can be difficult to diagnose the etiology. We present a case of a patient with a history of remote alcohol use disorder in remission and Roux-en-Y gastric bypass (RYGB) 20 years prior who was admitted for altered mental status, found to have hyperammonemia with normal liver function tests and a normal liver biopsy. An extensive workup was unremarkable until several weeks into her admission, where she was found to have osmotic demyelination syndrome on head MRI, which was obtained after she developed persistent myoclonus and opsoclonus. Her osmotic demyelination was speculated to be secondary to hyperammonemia, which itself was correlated to her history of RYGB. There have been multiple case reports on the association of late onset hyperammonemic encephalopathy after RYGB; however, no significant correlation has yet to be made between osmotic demyelination syndrome and hyperammonemia.

First structurally characterized tricyanomanganate(III) and its magnetic {Mn(III)(2)M(II)(2)} complexes (M(II) = Mn, Ni).

Treatment of tris(3-cyano-2,4-pentanedionato)manganese(III) with KTp*, followed by [NEt(4)]CN affords [NEt(4)][(Tp*)Mn(III)(CN)(3)] (1); subsequent treatment of 1 with divalent triflates (OTf) and 2,2'-bipyridine (bpy) affords {Mn(III)(2)M(II)(2)} complexes (M(II) = Mn, 2; Ni, 3). Magnetic measurements show that 1-3 exhibit S(T) = 1, 3, and 4 spin ground states, respectively.