A chromosome-scale fishing cat reference genome for the evaluation of potential germline risk variants.

The fishing cat, Prionailurus viverrinus, faces a population decline, increasing the importance of maintaining healthy zoo populations. Unfortunately, zoo-managed individuals currently face a high prevalence of transitional cell carcinoma (TCC), a form of bladder cancer. To investigate the genetics of inherited diseases among captive fishing cats, we present a chromosome-scale assembly, generate the pedigree of the zoo-managed population, reaffirm the close genetic relationship with the Asian leopard cat (Prionailurus bengalensis), and identify 7.4 million single nucleotide variants (SNVs) and 23,432 structural variants (SVs) from whole genome sequencing (WGS) data of healthy and TCC cats. Only BRCA2 was found to have a high recurrent number of missense mutations in fishing cats diagnosed with TCC when compared to inherited human cancer risk variants. These new fishing cat genomic resources will aid conservation efforts to improve their genetic fitness and enhance the comparative study of feline genomes.

Cancer control collaborations between China and African countries.

Over the past decade, China has emerged as Africa's largest trade partner and source of foreign direct investment, with public health ranked as a top priority in China-Africa collaborations. During the same period, cancer has emerged as a leading cause of death in Africa, with more than 700 000 deaths per year and projections of more than 1 million deaths per year by 2030. In this Review, we explore the effects of increasing China-Africa collaborations on cancer control in Africa. We review the published literature on health-care assistance, research, education and training, and infrastructure and present the results of an institutional review board-approved survey of African oncology health-care professionals and institutional leaders that assessed their perception of the effects of China-Africa collaborations. From peer-reviewed articles and grey literature, we found that the number of China-Africa collaborations have grown substantially over the past decade in different areas, especially in patient care and infrastructure. Research publications have also surged in quantity in the past decade compared with previous years. However, the survey results suggest research collaborations remain infrequent and that medical professionals in African cancer centres rarely participate in direct research collaborations with Chinese institutions. The Review also highlights the challenges and benefits of increasing China-Africa collaborations. Challenges include insufficient monitoring and evaluation of the projects in Africa and poor coordination and alignment of the various initiatives. The benefits of these collaborations for Africa include improved health outcomes, strengthened health systems, and socioeconomic development. Benefits are also apparent for China, such as securing energy and resource supplies, expanded trade and investment opportunities, and improved diplomatic relations. Overall, China-Africa collaborations are increasing and having a substantial effect in both China and the African continent. Recommendations to minimise the challenges and maximise the benefits for more positive consequences on cancer control in Africa are discussed.

Durable contraception in the female domestic cat using viral-vectored delivery of a feline anti-Müllerian hormone transgene.

Eighty percent of the estimated 600 million domestic cats in the world are free-roaming. These cats typically experience suboptimal welfare and inflict high levels of predation on wildlife. Additionally, euthanasia of healthy animals in overpopulated shelters raises ethical considerations. While surgical sterilization is the mainstay of pet population control, there is a need for efficient, safe, and cost-effective permanent contraception alternatives. Herein, we report evidence that a single intramuscular treatment with an adeno-associated viral vector delivering an anti-Müllerian hormone transgene produces long-term contraception in the domestic cat. Treated females are followed for over two years, during which transgene expression, anti-transgene antibodies, and reproductive hormones are monitored. Mating behavior and reproductive success are measured during two mating studies. Here we show that ectopic expression of anti-Müllerian hormone does not impair sex steroids nor estrous cycling, but prevents breeding-induced ovulation, resulting in safe and durable contraception in the female domestic cat.

Smart Radiotherapy Biomaterials for Image-Guided In Situ Cancer Vaccination.

Recent studies have highlighted the potential of smart radiotherapy biomaterials (SRBs) for combining radiotherapy and immunotherapy. These SRBs include smart fiducial markers and smart nanoparticles made with high atomic number materials that can provide requisite image contrast during radiotherapy, increase tumor immunogenicity, and provide sustained local delivery of immunotherapy. Here, we review the state-of-the-art in this area of research, the challenges and opportunities, with a focus on in situ vaccination to expand the role of radiotherapy in the treatment of both local and metastatic disease. A roadmap for clinical translation is outlined with a focus on specific cancers where such an approach is readily translatable or will have the highest impact. The potential of FLASH radiotherapy to synergize with SRBs is discussed including prospects for using SRBs in place of currently used inert radiotherapy biomaterials such as fiducial markers, or spacers. While the bulk of this review focuses on the last decade, in some cases, relevant foundational work extends as far back as the last two and half decades.

Challenges and opportunities for implementing hypofractionated radiotherapy in Africa: lessons from the HypoAfrica clinical trial.

The rising cancer incidence and mortality in sub-Saharan Africa (SSA) warrants an increased focus on adopting or developing approaches that can significantly increase access to treatment in the region. One such approach recommended by the recent Lancet Oncology Commission for sub-Saharan Africa is hypofractionated radiotherapy (HFRT), which can substantially increase access to radiotherapy by reducing the overall duration of time (in days) each person spends being treated. Here we highlight challenges in adopting such an approach identified during the implementation of the HypoAfrica clinical trial. The HypoAfrica clinical trial is a longitudinal, multicentre study exploring the feasibility of applying HFRT for prostate cancer in SSA. This study has presented an opportunity for a pragmatic assessment of potential barriers and facilitators to adopting HFRT. Our results highlight three key challenges: quality assurance, study harmonisation and machine maintenance. We describe solutions employed to resolve these challenges and opportunities for longer term solutions that can facilitate scaling-up use of HFRT in SSA in clinical care and multicentre clinical trials. This report provides a valuable reference for the utilisation of radiotherapy approaches that increase access to treatment and the conduct of high-quality large-scale/multi-centre clinical trials involving radiotherapy. Trial registration: Not available yet.

Cancer in sub-Saharan Africa: a Lancet Oncology Commission.

In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.

Practical Guidelines on Implementing Hypofractionated Radiotherapy for Prostate Cancer in Africa.

Among a growing body of literature in global oncology, several articles project increased cost savings and radiotherapy access by adopting hypofractionated radiotherapy (HFRT) in low- and middle-income countries (LMICs) like those in Africa. Clinical trials in Europe and the USA have demonstrated HFRT to be non-inferior to conventional radiotherapy for eligible patients with several cancers, including prostate cancer. This could be a highly recommended option to battle a severely large and growing cancer burden in resource-limited regions. However, a level of implementation research may be needed in limited resource-settings like in Africa. In this article, we present a list of evidence-based recommendations to practice HFRT on eligible prostate cancer patients. As literature on HFRT is still developing, these guidelines were compiled from review of several clinical trials and professionally accredited material with minimal resource requirements in mind. HFRT guidelines presented here include patient eligibility, prescription dose schedules, treatment planning and delivery techniques, and quality assurance procedures. The article provides recommendations for both moderately hypofractionated (2.4-3.4Gy per fraction) and ultrahypofractionated (5Gy or more per fraction) radiation therapy when administered by 3D-Conformal Radiotherapy, Intensity Modulated Radiation Therapy, or Image-Guided Radiotherapy. In each case radiation oncology health professionals must make the ultimate judgment to ensure safety as more LMIC centers adopt HFRT to combat the growing scourge of cancer.

Optimizing In Situ Vaccination During Radiotherapy.

Effective in situ cancer vaccines require both a means of tumor cell death and a source of adjuvant to activate local dendritic cells. Studies have shown that the use of radiotherapy (RT) to induce tumor cell death and anti-CD40 to activate dendritic cells can result in in situ vaccination in animal models. Here, investigations are carried out on potential strategies to enhance such in situ vaccination. Strategies investigated include the use of smart immunogenic biomaterials (IBM) loaded with anti-CD40 in different tumor types including immunologically cold tumors like pancreatic and prostate tumors. The use of downstream checkpoint inhibitors to further boost such in situ vaccination is also examined. Results indicate that the use of IBM to deliver the anti-CD40 significantly enhances the effectiveness of in situ vaccination with anti-CD40 compared with direct injection in pancreatic and prostate cancers (p < 0.001 and p < 0.0001, respectively). This finding is consistent with significant increase in infiltration of antigen-presenting cells in the treated tumor, and significant increase in the infiltration of CD8+ cytotoxic T lymphocyte into distant untreated tumors. Moreover, in situ vaccination with IBM is consistently observed across different tumor types. Meanwhile, the addition of downstream immune checkpoint inhibitors further enhances overall survival when using the IBM approach. Overall, the findings highlight potential avenues for enhancing in situ vaccination when combining radiotherapy with anti-CD40.

Can the Adoption of Hypofractionation Guidelines Expand Global Radiotherapy Access? An Analysis for Breast and Prostate Radiotherapy.

PURPOSE: The limited radiotherapy resources for global cancer control have resulted in increased interest in developing time- and cost-saving innovations to expand access to those resources. Hypofractionated regimens could minimize cost and increase access for limited-resource countries. In this investigation, we estimated the percentage cost-savings per radiotherapy course and increased radiotherapy access in African countries after adopting hypofractionation for breast and prostate radiotherapy. For perspective, results were compared with high-income countries. METHODS: The cost and course of breast and prostate radiotherapy for conventional and hypofractionated regimens in low-resource facilities were calculated using the Radiotherapy Cost Estimator tool developed by the International Atomic Energy Agency (IAEA) and then compared with another activity-based costing model. The potential maximum cost savings in each country over 7 years for breast and prostate radiotherapy were then estimated using cancer incidence data from the Global Cancer Observatory database with use rates applied. The increase in radiotherapy access was estimated by current national capacities from the IAEA directory. RESULTS: The estimated cost per course of conventional and hypofractionated regimens were US$2,232 and $1,339 for breast treatment, and $3,389 and $1,699 for prostate treatment, respectively. The projected potential maximum cost savings with full hypofractionation implementation were $1.1 billion and $606 million for breast and prostate treatment, respectively. The projected increase of radiotherapy access due to implementing hypofractionation varied between +0.3% to 25% and +0.4% to 36.0% for breast and prostate treatments, respectively. CONCLUSION: This investigation demonstrates that adopting hypofractionated regimens as standard treatment of breast and prostate cancers can result in substantial savings and increase radiotherapy access in developing countries. Given reduced delivery cost and treatment times, we anticipate a substantial increase in radiotherapy access with additional innovations that will allow progressive hypofractionation without compromising quality.

Hypofractionated Radiotherapy in African Cancer Centers.

In the advent of the coronavirus disease (COVID-19) pandemic, professional societies including the American Society for Radiation Oncology and the National Comprehensive Cancer Network recommended adopting evidence-based hypofractionated radiotherapy (HFRT). HFRT benefits include reduction in the number of clinical visits for each patient, minimizing potential exposure, and reducing stress on the limited workforce, especially in resource-limited settings as in Low-and-Middle-Income Countries (LMICs). Recent studies for LMICs in Africa have also shown that adopting HFRT can lead to significant cost reductions and increased access to radiotherapy. We assessed the readiness of 18 clinics in African LMICs to adopting HFRT. An IRB-approved survey was conducted at 18 RT clinics across 8 African countries. The survey requested information regarding the clinic's existing equipment and human infrastructure and current practices. Amongst the surveyed clinics, all reported to already practicing HFRT, but only 44% of participating clinics reported adopting HFRT as a common practice. Additionally, most participating clinical staff reported to have received formal training appropriate for their role. However, the survey data on treatment planning and other experience with contouring highlighted need for additional training for radiation oncologists. Although the surveyed clinics in African LMICs are familiar with HFRT, there is need for additional investment in infrastructure and training as well as better education of oncology leaders on the benefits of increased adoption of evidence-based HFRT during and beyond the COVID-19 era.

Using perimetric data to estimate ganglion cell loss for detecting progression of glaucoma: a comparison of models.

PURPOSE: Models relating perimetric sensitivities to ganglion cell numbers have been proposed for combining structural and functional measures from patients with glaucoma. Here we compared seven models for ability to differentiate progressing and stable patients, testing the hypothesis that the model incorporating local spatial scale would have the best performance. METHODS: The models were compared for the United Kingdom Glaucoma Treatment Study (UKGTS) data for the right eyes of 489 patients recently diagnosed with glaucoma. The SITA 24-2 program was utilised for perimetry and Stratus OCT fast scanning protocol for thickness of circumpapillary retinal nerve fibre layer (RNFL). The first analysis defined progression in terms of decline in RNFL thickness. The highest and lowest quintiles (22 subjects per group) were identified for change in thickness of inferior temporal (IT), superior temporal (ST), and global RNFL (µm year-1 ); a two-way anova was used to look for differences between the models in ability to discriminate the two quintiles. The second analysis defined a 'progression group' as those who were flagged by the UKGTS criteria as having progressive loss in perimetric sensitivity, and a 'no progression' group as those with rate of change in Mean Deviation (MD) closest to 0 dB year-1 (87 subjects per group). The third analysis characterised variability of retinal ganglion cell (RGC) models for the two groups in the second analysis, using the standard deviation of residuals from linear regression of ganglion cell number over time to compute Coefficient of Variation (CoV). RESULTS: The first analysis produced a negative result because the three anovas found no effect of model or interaction of model and group (F6,294 < 3.1, p > 0.08). There was an effect of group only for the anova with the ST sector (F6,294 = 12.2, p < 0.001). The second analysis also produced a negative result, because ROC areas were in the range 0.69-0.72 for all models. The third analysis found that even when variability in MD was low, the CoV was so large that test-retest variation could include 100% loss of ganglion cells. CONCLUSIONS: Two very different approaches for testing the hypothesis both gave a negative result. For all seven ganglion cell models, rates of ganglion cell loss were highly affected by fluctuations in height of the hill of vision. Methods for reducing effects of between-visit variability are needed in order to assess progression by relating perimetric sensitivities and ganglion cell numbers.

A novel strategy for the estimation of the general height of the visual field in patients with glaucoma.

BACKGROUND: More accurate estimation of the general height of the visual field may improve our ability to detect and monitor progression of diseases affecting visual function such as glaucoma. General height (GH) can be affected by factors such as cataracts, pupillary miosis, refractive error, and learning and fatigue effects. The conventional GH index, consisting of subtracting the 85th largest value from the total-deviation map, has been shown to overestimate the height in patients with moderate and advanced glaucoma. We aimed at developing an improved estimator for general height based on ranking of total-deviation values that are within normal limits (GHr). METHODS: Two datasets were used for the comparisons between GH and GHr estimates: one with 369 visual fields for 102 controls, and another with 500 visual fields for 124 patients. For controls, we compared the distributions of mean of total deviation (MD) and of mean of pattern deviation (MPD) derived from both the GH and the GHr estimates. For patients, we assessed agreement between both estimates and between pairs of consecutive visits. We also compared linear fits in progression analyses. All data were collected with 24-2 SITA Standard. RESULTS: For control subjects and patients with MD above -5.5 dB, estimates with the GHr estimator were not significantly different than with the GH estimator. For patients with glaucoma with MD below -5.5 dB, as MD became more negative the GH estimates were increasingly greater than GHr estimates. For patients with glaucoma, test-retest variability was lower with the GHr estimator: between visits agreement was better for GHr estimates than for GH estimates (SD of 0.8 dB versus 1.5 dB; p < 0.0001). Linear-regression analysis fitted better estimates obtained with the GHr estimator. Root mean square error for GHr was 0.4 dB; lower than the 0.8 dB for GH (p < 0.0001). CONCLUSIONS: The novel GHr estimator is very different from the conventional GH estimator, has more solid foundations, and better statistical properties. Nevertheless, it is not always better than the GH estimator, in particular if no focal loss is present. Pattern-deviation maps obtained with GHr reduce systematic underestimation of glaucomatous damage.

Laparoscopic oviductal artificial insemination improves pregnancy success in exogenous gonadotropin-treated domestic cats as a model for endangered felids.

Artificial insemination (AI) in cats traditionally uses equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) to induce follicular development and ovulation, with subsequent bilateral laparoscopic intrauterine insemination. However, long-acting hCG generates undesirable secondary ovulations in cats. Uterine AI also requires relatively high numbers of spermatozoa for fertilization (~8 × 10(6) sperm), and unfortunately, sperm recovery from felids is frequently poor. Using short-acting porcine luteinizing hormone (pLH) instead of hCG, and using the oviduct as the site of sperm deposition, could improve fertilization success while requiring fewer spermatozoa. Our objectives were to compare pregnancy and fertilization success between 1) uterine and oviductal inseminations and 2) eCG/hCG and eCG/pLH regimens in domestic cats. Sixteen females received either eCG (100 IU)/hCG (75 IU) or eCG (100 IU)/pLH (1000 IU). All females ovulated and were inseminated in one uterine horn and the contralateral oviduct using fresh semen (1 × 10(6) motile sperm/site) from a different male for each site. Pregnant females (11/16; 69%) were spayed approximately 20 days post-AI, and fetal paternity was genetically determined. The number of corpora lutea (CL) at AI was similar between hormone regimens, but hCG increased the number of CL at 20 days post-AI. Numbers of pregnancies and normal fetuses were similar between regimens. Implantation abnormalities were observed in the hCG group only. Finally, oviductal AI produced more fetuses than uterine AI. In summary, laparoscopic oviductal AI with low sperm numbers in eCG/hCG- or eCG/pLH-treated females resulted in high pregnancy and fertilization percentages in domestic cats. Our subsequent successes with oviductal AI in eCG/pLH-treated nondomestic felids to produce healthy offspring supports cross-species applicability.

Characterization of basal seminal traits and reproductive endocrine profiles in North American river otters and Asian small-clawed otters.

In this study, fecal samples were collected from 24 North American river (NARO) and 17 Asian small-clawed otters (ASCO) for 6-36 months and semen collected seasonally from NARO males (n=4/season) via electroejaculation. Our main objectives were to: (1) characterize endocrine parameters by longitudinal monitoring of fecal hormone metabolites and (2) investigate semen collection and basal seminal traits in NARO. NARO demonstrated a distinct seasonality in the spring, with females having a monoestrual estrogen elevation lasting 15.33+/-1.98 (mean+/-SEM) days and males peaking in testosterone production for 25.50+/-7.51 days. Pregnancy was characterized by 7-9 months of basal fecal progesterone, presumably corresponding to embryonic diapause, followed by a rapid increase over the final 68-73 days to term. Pseudopregnancy exhibited a similar late winter progesterone peak of 68-72 days, which could not be differentiated from pregnancy. Geographic latitude possibly influenced the timing of increased testosterone in males and increased progesterone in pregnant/pseudopregnant females. In ASCO, monitoring of fecal estrogens did not allow consistent detection of peak values associated with behavioral estrus. Both pregnancy and pseudopregnancy were characterized by a moderate rise in fecal progesterone for 14-16 days postovulation followed by a marked increase. Total gestation length was 67-77 days compared with 62-84 days for pseudopregnancy. In NARO, optimal sperm recovery and quality occurred only in the spring, corresponding with seasonal increases in testicular volume and fecal testosterone. These findings represent the first comprehensive information on normative endocrine and seminal traits in freshwater otter species.

Refinement of a commercial bench-top relaxin assay for pregnancy diagnosis using urine from domestic and nondomestic felids.

Relaxin, a 6-kDa polypeptide hormone, is excreted in the urine during pregnancy in several mammalian species. A recent study showed that detection of urinary relaxin using a bench-top serum assay (Witness relaxin kit, Synbiotics Corp., San Diego, California 92127, USA) can be diagnostic for pregnancy in domestic cats (Felis silvestris catus), but it is unknown whether the bench-top kit is applicable with urine across felid species. Our objectives were to 1) examine modifications in urine processing to improve kit reliability in pregnant cats, 2) evaluate the impact of concentrating urine via filtration on relaxin detection, 3) assess the effect of sample freezing on relaxin concentrations, and 4) begin quantifying urinary relaxin levels in nondomestic felids. Urine and serum were collected from domestic cats and nondomestic cat species (Pallas' cat, Otocolobus manul; sand cat, Felis margarita; cheetah, Acinonyx jubatus; and lion, Panthera leo) at several times after breeding. Urine samples, subjected to various processing methods, were tested using the bench-top kit, and relaxin levels were later quantified via radioimmunoassay. For domestic cat urine samples, filtration and addition of protein/phosphate buffer improved the consistency of the relaxin kit for early pregnancy diagnosis. Urine freezing caused a slight (approximately 13%) but significant decrease in relaxin concentrations, but frozen-thawed samples still tested positive with the bench-top kit. In nondomestic felids, urinary relaxin immunoreactivity during pregnancy was similar to or higher than that of pregnant domestic cats, suggesting that relaxin is a reliable cross-species marker of pregnancy. Urinary relaxin was detectable using the bench-top kit in pregnant Pallas' cats, but urine samples from other species tested negative, regardless of processing methods. Findings suggest that measurement of urinary relaxin is a promising approach for noninvasive pregnancy diagnosis in exotic felids, but further assessment of urinary relaxin profiles among cat species and modification of the bench-top relaxin kit are warranted to improve cross-species utility.

Use of a magnetic sphincter for the treatment of GERD: a feasibility study.

BACKGROUND: The success of fundoplication surgery varies widely; furthermore, complications after fundoplication can be common. We introduced a new device to treat GERD: biomechanical augmentation of the lower esophageal sphincter (LES) by use of a magnetic reinforcing appliance. OBJECTIVES: The aim was to determine whether a magnetic appliance could safely increase LES pressure, maintain a closed sphincter except during swallowing and belching, and increase the gastric yield pressure in a porcine model. DESIGN: Ex vivo work-assessed design variables that would augment the reflux barrier yet still preserve swallow function. Porcine acute and chronic (44 weeks) postimplant studies were also performed. A single animal underwent planned device removal. MAIN OUTCOME MEASUREMENTS: Gastric yield pressure, animal behavior, endoscopy, barium studies, balloon expansion studies, esophageal manometry, and histology. RESULTS: Gastric yield pressure correlated with increasing magnetic forces (R(2)=0.5608, P< .001). The sphincter augmentation device was safe in all animals, with no observed effect on eating behavior and normal weight gain. The mucosa of the esophagus appeared normal at all intervals, and there was no device migration or significant tissue inflammation. The average LES pressure rose after implantation (P< .005). Balloon and barium studies demonstrated a closed sphincter with normal opening of the gastroesophageal junction during swallowing. CONCLUSIONS: Magnetic sphincter augmentation is a novel approach for the treatment of GERD. This study demonstrates the safety and feasibility of such a device in a porcine model. Further investigation of this device for the treatment of GERD in humans seems warranted.

An experimental model of saphenous vein-to-coronary artery anastomosis with the St. Jude Medical stainless steel connector.

BACKGROUND: A new stainless steel anastomosis device developed by St. Jude Medical Cardiovascular Group was studied in a canine model. METHODS: In 12 dogs, coronary saphenous vein grafts were made to the left anterior descending coronary artery and to the circumflex coronary artery; one anastomosis was completed with the St. Jude Medical stainless steel connector device, and the other with conventional suturing. A 30-day coronary angiogram was performed in surviving animals, and, after sacrifice, anastomoses were measured, examined grossly, and submitted for histologic study. RESULTS: All 12 animals survived the procedure, and 9 survived to sacrifice at 30 days. Comparing the connector grafts and sutured grafts, no significant differences were found between vessel diameters, intraoperative graft flows, graft patency, and histology. The average loading time for the connector was 8.5 minutes (range 4 to 16 minutes). Mean time for the 12 connector anastomoses was 3 minutes (range 2 to 5 minutes) compared with 8.4 minutes for suture (range 4 to 13 minutes). CONCLUSIONS: The side-to-side stainless steel connector anastomotic device produces a secure anastomosis with minimal variability; compared with suture methods, it is expeditious and has comparable 30-day histology and angiographic results. It promises to be an important addition to the surgical armamentarium for the treatment of coronary artery disease.