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Background: Sodium glucose cotransporter-2 inhibitors (SGLT2is) are hypothesized to reduce the risk of anthracycline-associated cardiotoxicity., Objectives: This study sought to determine the association between SGLT2is and cardiovascular disease (CVD) after anthracycline-containing chemotherapy., Methods: Using administrative data sets, we conducted a population-based cohort study of people >65 years of age with treated diabetes and no prior heart failure (HF) who received anthracyclines between January 1, 2016, and December 31, 2019. After estimating propensity scores for SGLT2i use, the average treatment effects for the treated weights were used to reduce baseline differences between SGLT2i-exposed and -unexposed controls. The outcomes were hospitalization for HF, incident HF diagnoses (in- or out-of-hospital), and documentation of any CVD in future hospitalizations. Death was treated as a competing risk. Cause-specific HRs for each outcome were determined for SGLT2i-treated people relative to unexposed controls., Results: We studied 933 patients (median age 71.0 years, 62.2% female), 99 of whom were SGLT2i treated. During a median follow-up of 1.6 years, there were 31 hospitalizations for HF (0 in the SGLT2i group), 93 new HF diagnoses, and 74 hospitalizations with documented CVD. Relative to controls, SGLT2i exposure was associated with HR of 0 for HF hospitalization ( P < 0.001) but no significant difference in incident HF diagnosis (HR: 0.55; 95% CI: 0.23-1.31; P = 0.18) or CVD diagnosis (HR: 0.39; 95% CI: 0.12-1.28; P = 0.12). There was no significant difference in mortality (HR: 0.63; 95% CI: 0.36-1.11; P = 0.11)., Conclusions: SGLT2is may reduce the rate of HF hospitalization after anthracycline-containing chemotherapy. This hypothesis warrants further testing in randomized controlled trials., Competing Interests: Analysis of this study was funded by the Ted Rogers Centre for Heart Research (to Dr Thavendiranathan). Dr Abdel-Qadir is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada. Dr Thavendiranathan is supported by a Tier II Canada Research Chair in CardioOncology. The funding sources had no role in the conduct of the study, the decision to publish or the preparation of the manuscript. Dr Abdel-Qadir has received honoraria from Amgen, AstraZeneca, and Jazz Pharmaceuticals. Dr Thavendiranathan has received speaker honoraria from Amgen, Boehringer Ingelheim, and Takeda. This study was supported by ICES, an independent, nonprofit research institute funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). Parts of this material are based on data and/or information compiled and provided by Ontario Health, the Ontario Ministry of Health, and the Canadian Institute of Health Information (CIHI). Parts of this report are based on Ontario Registrar General information on deaths, the original source of which is Service Ontario. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources (ICES, CIHI, Ontario Health, ORG, or the Ontario MOH/ MLTC); no endorsement is intended or should be inferred. Dr Neilan has been a consultant to and received fees from Bristol Myers Squibb, Genentech, CRC Oncology, Roche, Sanofi and Parexel Imaging Pharmaceuticals, outside of the current work. Dr Neilan also reports grant funding from Astra Zeneca and Bristol Myers Squibb outside of the current work. Dr Neilan is supported by a gift from A. Curt Greer and Pamela Kohlberg and from Christina and Paul Kazilionis, the Michael and Kathryn Park Endowed Chair in Cardiology, a Hassenfeld Scholar Award, and has additional grant funding from the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL137562, K24HL150238). All other authors have reported that they have no relationships to the contents of this paper to disclose., (© 2023 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Two experiments were conducted to compare a sample of calcium citrate-malate (CC-M) with a sample of commercial-grade limestone in starting broiler chick diets. In the first experiment, with 0.7 or 0.9% calcium from limestone or CC-M, no differences in bone development (dry fat-free tibia, tibia weight, tibia ash, or tibia calcium) were observed due to calcium source. However, chicks fed the diets based on CC-M had better 0- to 18-d body weight gains and feed conversion ratios than those fed limestone. In the second experiment with 0.50, 0.55, 0.60, 0.65, or 0.70% calcium from limestone or CC-M, chicks again had better body weight gains when fed CC-M compared to those fed limestone. Chicks fed diets based on CC-M and NaP2PO4 had very similar bone development and tibial dyschondroplasia pathology to those fed limestone and Na2H2PO4. However, a control group of chicks fed 0.70% calcium from limestone and dicalcium phosphate did not grow as well as the others and had lower weights of tibia and tibial bone ash, calcium, and phosphorus compared to the others. It is concluded that CC-M is a good calcium source, comparable in bioavailability to limestone. Although CC-M may improve broiler growth, its action is not through increased bioavailability of calcium.

Three experiments were conducted to evaluate the performance of broiler chicks fed diets with cottonseed meal (CSM) as the major protein source. Experiment 1 was a 3 x 2 factorial with three crude protein levels (17, 20, and 23%) by two protein sources, CSM or soybean meal (SBM). Diets were fed to male broilers (n = 840) in floor pens from 21 to 49 d of age. L-Lysine-HCl was added to keep lysine at 5.22% of protein. Protein source and level had significant (P < 0.001) effects on BW gain (BWG) and feed conversion ratio (FCR), respectively (no source by level interactions). The average BWG were 1.80, 2.00, and 2.00 kg for birds fed CSM-based diets, compared with 1.93, 2.09, and 2.21 for SBM-based diets (17, 20, and 23% protein, respectively). The average FCR were 2.56, 2.31, and 2.25 for CSM-fed broilers and 2.39, 2.16, and 2.08 for SBM-fed broilers. Significant effects of protein source or level were found for percentage of chilled carcass, fillets, tenders, saddles, and fat pads. In Experiment 2, male broiler chicks (n = 336) were used to determine the lysine requirement of chicks fed a corn and CSM-based diet with 20% CSM and 6% SBM. The basal diet contained by calculation 3,200 kcal/kg of ME, 20% CP, and 0.81% lysine. Graded levels of lysine (0.81 to 1.30% in increments of 0.07%) were fed to chicks from 10 to 20 d, and BW and residual feed were measured at 20 d. The requirement, as determined by breakpoint analysis, was 1.023+/-0.01% lysine (R2 = 0.84) for BWG and 1.028+/-0.02% lysine (R2 = 0.56) for FCR. In Experiment 3, a 2 x 2 x 4 factorial arrangement of treatments involved feeding CSM or SBM to male and female broiler chicks (n = 768) from 21 to 42 d at four dietary protein levels (17, 20, 23, and 26% CP). Lysine was kept at 5.5% of the dietary protein and consisted of the calculated minimum level, established in Experiment 2, plus 7%. Protein level, but not source, had a significant effect on BWG and FCR (P < 0.01 and P < 0.001, respectively) for males. The average BWG were 1.53, 1.74, 1.78, and 1.81 kg for birds fed CSM compared to 1.46, 1.72, 1.84, and 1.82 kg for those fed SBM (17, 20, 23, and 26% CP, respectively); average FCR were 2.36, 2.14, 2.05, and 1.97 for CSM compared to 2.35,2.04, 1.87, and 1.80 for SBM. Protein source and level significantly (P < 0.05) affected feed intake. Significant effects of protein source or level were found for percentage carcass, fillet, tenders, leg quarters, and fat pads. Females had similar qualitative responses. This study showed that at slightly higher protein levels CSM could replace SBM in broiler grower diets to achieve similar performance.

Three experiments were conducted to test the hypothesis that extruding cottonseed meal (CSM) with supplemental lysine improves its feeding value by detoxifying gossypol. The performance of 1-wk-old straight-run Peterson x Arbor Acres broiler chicks fed diets containing 20% feed-grade or extruded CSM was compared with that of control chicks fed corn and soybean meal-based broiler rations. All diets were formulated to meet minimum NRC requirements. Lysine levels were adjusted by addition of synthetic lysine at rates of 0.5 to 2.0% of the protein in CSM. In all experiments, weight gain, feed intake, and feed conversion ratio (FCR) of broilers at 21 d were significantly affected by the diets. Feeding feed-grade and extruded CSM resulted in decreased body weight gain, increased feed intake, and inefficient feed utilization. When 2% lysine was added to feed-grade or extruded CSM, the body weight gains of chicks were not significantly different from those fed the control diet. The FCR of chicks fed feed-grade and extruded CSM plus 2% lysine at 21 d was significantly better than that of chicks fed feed-grade or extruded CSM alone. Abdominal fat pads (as a percentage of body weight) were significantly increased by the inclusion of CSM with or without the addition of lysine (P < or = 0.019). Liver, spleen, and heart weights were not affected by the presence of 20% CSM in the diet. The effects of CSM on plasma iron level was not consistent. Only in Experiment 1 did CSM cause a significant reduction in plasma iron. The hemoglobin contents and hematocrit values of blood from chicks fed diets with 20% CSM were not significantly different from those of the controls. The extrusion process reduced the free gossypol in CSM, but the total gossypol level was not changed, and chick performance was not improved. However, this study shows that, with adequate supplemental lysine, CSM can be used in broiler diets without a reduction in performance.

Three recently described and toxicologically important mycotoxins, fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3), produced by Fusarium moniliforme in various grains, have been associated with a number of diseases in both humans and animals. The toxicity of purified FB1, FB2, and FB3, individually and in combination (3:1:1 ratio), were evaluated with regard to their embryo toxicity by injection of the toxins into the air cell of chicken eggs at 72 h of incubation. Under these conditions, FB1 at doses of 0, 2, 4, 8, 16, 32, and 64 microg per egg resulted in embryonic mortality of 5, 12.5, 17.5, 20.0, 52.5, 77.5, and 100%, respectively. The 50% lethal dose for FB1, when injected into the air cell of embryonating chicken eggs, was determined to be 18.73 microg per egg. A comparison of the toxicity of FB1, FB2, and FB3, individually and in combination (3:1:1 ratio), at doses of 16 microg of total fumonisin per egg, indicated that the toxicity of the fumonisins differed, FB1 being the most toxic. Microscopic examination of chicken embryos exposed to fumonisin did not reveal any gross developmental abnormalities; however, severe hemorrhages of the head, neck, and thoracic area of the dead embryos were evident.

An investigation of the toxicity of fumonisin B1 (FB1), a toxic metabolite of Fusarium moniliforme, in broiler chicks was conducted. Purified FB1 (98.1% pure) was incorporated into the diets of broiler chicks at 0, 20, 40, and 80 mg/kg, and fed to chicks from 0 to 21 d of age. Dietary FB1, at concentrations of 80 mg/kg or less, did not adversely affect body weight, feed efficiency, or water consumption of broiler chicks. The relative weights of the liver, spleen, kidney, proventriculus, and bursa of Fabricius were also unaffected (P < 0.05) by any dietary concentration of FB1 compared with the control (0 mg/kg) group. Total liver lipids of chicks fed 40 or 80 mg FB1/kg were significantly lower than those of the chicks fed either 0 or 20 mg FB1/kg of feed. Liver sphinganine concentration and the sphinganine:sphingosine ratio were increased significantly in all treated groups. Chicks fed dietary FB1 at 80 mg/kg had significantly higher serum glutamate oxaloacetate aminotransaminase:aspartate aminotransferase ratios and levels of free sphinganine in the serum. The results of this investigation agree with the results previously described, in which FB1 was supplied to diets from the use of F. moniliforme-contaminated grain; therefore, the use of such material as the source of the mycotoxin in animal feeding studies is appropriate.

It was the purpose of these experiments to describe gonadal development and posthatching growth of genetic female chickens and turkeys following in ovo injection of the aromatase inhibitor Fadrazole (CGS 16949A) prior to incubation. In ovo injection of Fadrazole (CGS 16949A) resulted in the development of testes-like gonads in the majority of day-old genetic female chickens and turkey poults. Ninety-eight to 99% of these birds have masculine-type male genitalia at 1 d of age. Microscopic examination of the gonads of day-old genetic female chicks hatched from Fadrazole-treated eggs showed the presence of atypical seminiferous tubules in 3 of 18 individuals and the presence of ovarian follicles in 3 of 18 individuals. No germinal elements were seen in 12 individuals. The gonads in the majority (8/11) of day-old female poults from treated eggs showed the presence of atypical seminiferous tubules. Three of 11 individuals had structures characterized as disorganized or degenerate follicles. Between the day of hatch and 6 wk, gonads in an increasing proportion of female chickens from Fadrazole-treated eggs had normal appearing ovarian follicles. A similar trend was seen in the female turkeys between hatch and 12 wk of age. There were no differences in BW of female chickens hatched from Fadrazole-treated eggs and those from control eggs between the day of hatch and 6 wk of age. The pectoral muscle mass and fat pad weights of these birds did not differ. In one experiment, the BW of female turkeys hatched from Fadrazole-treated eggs was significantly greater than that of controls and equal to that of males at 3 and 6 wk of age. Thereafter, both types of females were of equal weight and significantly lighter than males. Fadrazole treatment did not affect pectoral muscle mass of either sex of turkeys.

Based on earlier studies from our laboratory, we hypothesized that higher levels of plasma androgens in male embryos stimulate greater muscle development and are responsible for the greater muscle mass of male chickens after hatching. The results of these studies show that androgen supplementation by in ovo injection of testosterone prior to incubation had no effect on weight of 12-, 16-, or 20-d-old male chicken embryos or on characteristics of their Pectoralis superficialis muscle. In contrast, weight of 12 d-old female embryos was depressed and the protein concentration and protein content of the P. superficialis was reduced in 16-d-old female embryos. Interference with the actions of endogenous androgens by preincubation in ovo injection of Flutamide, an antiandrogen, resulted in significant linear and quadratic relationships between the dose of Flutamide injected and the weight, protein content, and DNA content of the P. superficialis of 16-d-old female embryos. Increases over the lower part of the dose range (0 to 1.74 micromol per egg) were followed by a decrease at the highest dose (2.9 micromol per egg). The DNA content of the P. superficialis of 16-d-old female embryos was similarly affected when Flutamide was injected on Day 8 of incubation, whereas the protein content and protein concentration of the muscle was increased in 20-d-old female embryos. There were no significant changes in the weight, protein content, or DNA content of the P. superficialis of male embryos when Flutamide was injected before or on Day 8 of incubation.

Body growth, muscle growth, bone growth, and measurements of muscle fiber area and fiber number were made in a line of Japanese quail (Coturnix coturnix japonica) selected for high 4 week body weight for 100 generations (line PP), in the control line from which they were derived (line CC), and in genetically equivalent reciprocal crosses (PC and CP) that develop in eggs that differ greatly in weight. There was no difference in body weight or weight of the P. superficialis of newly hatched CC or PC quail. Weights of PP and CP were equal to each other but greater than those of CC and PC. Body and muscle weights of the crosses were equal by 3 to 4 weeks of age. The number of fibers in the Semimembranosus muscle was lowest in CC quail, intermediate in PC and CP quail, and greatest in PP. Cross-sectional area of Semimembranosus fibers from 7 day old CC and PC were equal to each other and smaller than those of PP or CP quail. By 29 days of age, fibers in CC were smallest, those in PC and CP were intermediate and smaller than those of PP quail. At 7 days, the cross-sectional area of P. superficialis fibers of CP quail was greater than those of the other genotypes, but by 14 days and after fiber area was directly related to the bird's genetic potential for growth. These studies show that fiber hyperplasia is genetically determined whereas fiber hypertrophy in early life is primarily dependent on the dam's genotype and egg environment.

Studies were conducted to compare the weights and the characteristics of the Pectoralis superficialis, Semimembranosus, and Gastrocnemius of male and female chicken embryos at 16 and 20 d of incubation. Male embryos were significantly heavier than females at 16 d of incubation, but not at 20 d. The cross-sectional area of myofibers in the P. superficialis of 20-d-old female embryos was greater than that of males and the area of Semimembranosus myofibers was greater at 16 and 20 d. The Semimembranosus apparent myofiber number of 16-d-old male embryos was greater than of females (P = 0.002). There was a significant increase in apparent myofiber number in this muscle between 16 and 20 d of incubation but there was no sex difference at 20 d. The number of Type I myofibers per 30,000 microm2 area of the Gastrocnemius of 20-d-old male embryos was greater than that in females (P = 0.06). There were no significant sex differences in the protein concentration, DNA concentration, or protein:DNA ratio in the muscles at either age when data were pooled across the whole population. There were significant differences in these characteristics between sire families and in some sire families significant sex differences were noted. The protein:DNA ratio of the muscles increased between 16 and 20 d of incubation and the mitotic index decreased. These data suggest that the muscles of male embryos have more but smaller, myofibers than females, which may be responsible for the sex difference in embryo weight and provide the framework for the greater posthatching muscle growth.

Body weight and muscle characteristics of 18- to 20-d-old broiler strain embryos developing in double yolk eggs (DY) that contained one embryo and one infertile ovum were compared with embryos in single yolk eggs (SY). Similar comparisons were made in the posthatching period. In some DY eggs, the embryos were bathed in a watery yolk-like fluid with no distinct second yolk present (Type 1 embryo). In others, the second yolk was contained within the vitelline membrane and surrounded by a vascularized membrane (Type 2). These embryos were heavier than Type 1 or embryos in SY eggs by 20 d of incubation. Their Pectoralis superficialis were heavier and had significantly more protein and DNA. Chicks that hatched from the DY eggs were heavier than those that hatched from SY eggs and they had heavier P. superficialis through at least 14 d of age. Pectoralis superficialis myofibers of chicks from DY eggs had greater cross-sectional area than those from SY eggs. Myofibers in the Semimembranosus of 7- and 14 d-old chicks from DY eggs tended to be larger than those from SY eggs, but the differences were not significant. There was no difference in apparent myofiber number in the Semimembranosus of the two types of chicks. The difference in BW between the two types of chicks diminished over time, so that by 42 d of age they were virtually identical. In summary, a nutritionally enriched in ovo environment resulted in embryos and chicks with enhanced growth and muscle mass, but the effects of enrichment diminished during posthatching life and eventually disappeared.

At hatch, chicks from bantam sire x broiler dam (BaBr) matings were as heavy as those from broiler sire x broiler dam (BrBr) matings. Both were heavier than pure bantam chicks (BaBa) or chicks from broiler strain sires and bantam dams (BrBa), but weights of the latter two genotypes were identical. The Pectoralis superficialis and Semimembranosus of pure bantam chicks weighed less than those of pure broiler chicks throughout the studies. Muscle weights in the BaBr chicks were markedly heavier than those of genetically similar BrBa chicks at hatch. Genetic influences were quickly expressed and weights of muscles in these two groups had converged by 14 d of age. Myofiber cross-sectional areas at 1 d of age were not clearly associated with genotype or maternal environment, but clear patterns had begun to develop by 4 d of age. Myofiber area of both muscles was greater in BrBr than BaBa chicks by this age and after. Myofiber areas in the reciprocal crosses converged toward each other and away from the pure line chicks. By 11 d, the area of Pectoralis myofibers of BrBr chicks was greatest, those of the reciprocal crosses was intermediate and equal to each other, and that of BaBa chicks was least. A similar trend was apparent in Semimembranosus fibers by 11 d but the differences did not become significant until 21 d of age. Significant differences in myofiber number of the Semimembranosus were present (BrBr > BaBr > BrBa > BaBa). Thus, differences in muscle mass were the result of differences in both fiber number and fiber size.

We studied 62 patients (40 men and 22 women) with an average age of 28 years over a 28-month period who presented with shoulder pain that was refractory to 3 months of conservative management. Patients with a prior glenohumeral dislocation or a rotator cuff tear were excluded. The "crank" test was performed with the arm elevated to 160 degrees in the scapular plane of the body, loaded axially along the humerus, and with maximal internal and external rotation. Although similar tests have been described, the crank test is a new examination previously unreported. Half of the patients (31) had a positive crank test. Arthroscopy performed on all 62 patients revealed glenoid labral tears in 32 patients. Two patients who had positive crank tests did not have labral tears but had partial-thickness, articular-side rotator cuff tears. The sensitivity of the crank test was 91%, the specificity was 93%, the positive predictive value was 94%, and the negative predictive value was 90%. With these data, the crank test fulfills the criteria as a single physical examination test that is highly accurate for the preoperative diagnosis of glenoid labral tears. Accordingly, expensive imaging modalities currently used in this patient population may be employed less in the future.

We studied 54 patients with shoulder pain secondary to anterior instability or glenoid labral tears refractory to 6 months of conservative management with no evidence of rotator cuff lesions. All patients had sufficient preoperative clinical data, magnetic resonance imaging, and shoulder arthroscopy results for analysis. The ability to predict the presence of a glenoid labral tear by physical examination was compared with that of magnetic resonance imaging (conventional and arthrogram) and confirmed with arthroscopy. There were 37 men and 17 women (average age, 34 years) in the study group. Of this group, 64% were throwing athletes and 61% recalled specific traumatic events. Clinical assessment included history with specific attention to pain with overhead activities, clicking, and instances of shoulder instability. Physical examination included the apprehension, relocation, load and shift, inferior sulcus sign, and crank tests. Shoulder arthroscopy confirmed labral tears in 41 patients (76%). Magnetic resonance imaging produced a sensitivity of 59% and a specificity of 85%. Physical examination yielded a sensitivity of 90% and a specificity of 85%. Physical examination is more accurate in predicting glenoid labral tears than magnetic resonance imaging. In this era of cost containment, completing the diagnostic workup in the clinic without expensive ancillary studies allows the patient's care to proceed in the most timely and economic fashion. Glenoid labral tears have been associated with overhead throwing activities, trauma, and shoulder instability. Assessment of an athlete with shoulder pain should take into account a careful history of clicking sounds or catching, symptoms with overhead activities, reports of instability, or previous trauma. On physical examination, patients with labral tears often demonstrate objective instability with or without clicking or catching during glenohumeral rotation. Plain radiographs have not been helpful, and radiologists have relied on techniques from arthrogram to arthrotomogram, CT arthrogram, magnetic resonance imaging (MRI), and MR arthrogram to assist in the diagnosis. Various sensitivities and specificities have been reported for these tests. However, a large degree of intra- and interobserver variability has been demonstrated, and the degree to which these studies are helpful in preoperative planning has been questioned. No previous study to our knowledge has involved MRI in a direct comparison of other diagnostic modalities. Therefore, the purpose of this study is to investigate the accuracy of MRI and physical examination in the diagnosis of glenoid labral tears.

During the past several decades, the treatment of anterior shoulder instability has evolved substantially. Treatment initially was based on conservative management with rehabilitation protocols for shoulder girdle strengthening. Functionally disabling instability and recurrent dislocation precluded the acceptance of conservative management as the definitive treatment for all patients. Attention then was turned to open repair strategies. Despite generally positive results, a significant number of complications became evident. With time, however, techniques improved and surgical complications were lessened. As shoulder arthroscopy was more widely practiced, the surgical reconstruction of instability became significantly less invasive. A high learning curve has been associated with the new arthroscopic techniques, and higher redislocation rates than those of open procedures have limited their acceptance by many orthopaedic surgeons. This review article examines the anatomy and pathology of anterior shoulder dislocations, and critically reviews the actual laboratory and clinical data supporting use of these various treatment options. Only through careful examination of well-controlled scientific studies can clinicians devise their own treatment protocol for symptomatic anterior instability of the shoulder.

Acromioclavicular joint symptoms may originate from either osteolysis or osteoarthritis. Initial treatment consists of 6 to 12 months of physical therapy, nonsteroidal antiinflammatory drugs, avoidance of exacerbating activities, and other conservative modalities. The majority of patients respond well, but a few remain unable to return to their previous or desired activity levels. Previously this group of patients underwent open resection of the distal clavicle. [The approach violates the deltotrapezial fascia, weakening the surgically treated extremity, which has caused controversy in the literature.] Even without complications, the recovery and time away from work is prolonged. With advances in arthroscopic techniques, resection of the distal clavicle and medial aspect of the acromion has become possible with minimal invasiveness. The arthroscopic technique offers the advantages of rapid rehabilitation with excellent functional results. Several different modifications of 2 basic approaches, the bursal and direct superior, have been described by various authors. The authors sought to examine critically and review the data supporting the choice of arthroscopic surgery rather than an open technique, as well as the advantages of 1 arthroscopic approach over the other.