The surface measurement of aortic atherosclerosis: critical survey and comparison with histologic findings

Both the reproducibility of the surface measurements of aortic atherosclerosis and the agreement between gross inspective and histologic changes were evaluated. Aortas from male broad breasted white turkeys were chosen because of the high incidence of spontaneous and typical atherosclerotic lesions in this animal strain. Ten male turkeys were killed at 33 weeks of age. The aortas were removed including the iliac bifurcation and stained with Sudan III. Each aorta was processed blindly by four pathologists and a computerized planimeter to determine normal areas, sudanophilic areas and areas covered by plaques. The analysis of variance showed significant differences among the four pathologists' measurements of sudanophilic areas (P less than 0.01) and areas covered by plaques (P less than 0.001). The coefficients of variation among the four determinations made by one pathologist on the same aorta were 3.6% for total aortic area; 10.08% for sudanophilic area; 47.6% for the area covered by plaques. On each aorta histology was performed at the level where all the four pathologists recorded the same findings at inspection, namely a normal area, a sudanophilic area, and an area covered by plaques. Important discrepancies occurred between findings at inspection and those of histologic examination: the ten areas classified as "normal" by all the four pathologists at inspection were shown at histologic examination to be normal in only two cases. In one case a musculo-elastic layer and in seven cases a fibro-elastic layer were found. The ten areas classified as "sudanophilic" by all the observers showed a fibro-elastic layer in five cases, a musculo-elastic layer in two cases and normal findings in three cases. The ten areas classified as "covered by plaques" displayed a typical atherosclerotic plaque in all cases but one. In conclusion, our data indicate that the reproducibility of gross inspective methods is low. Important discrepancies exist between findings at inspection and histologic examinations. The relevance of these findings remains to be established as far as the assessment of human atherosclerosis is concerned.     

Caregiver perceptions of psychotropic medication in residential facilities

Direct caregivers (designated as "psychopaedic nurses" in New Zealand) in two public residential facilities were surveyed regarding their perceptions, opinions, and knowledge of psychotropic drugs. Of 276 individuals contacted, 227 (82%) returned usable questionnaires. The results indicated that unit supervisors (charge nurses) and unit doctors were perceived as wielding most influence on decisions regarding psychotropic drugs, whereas caregivers based outside residential units were seen as having little influence. Aggressive/destructive behavior and, to a smaller extent, self-injurious behavior were seen as the most likely problem behaviors to lead to medication use. Subjective measures were generally favored for assessing drug effects although, in a hypothetical "ideal" situation, nurses gave increasing priority to more objective indices. Endorsement of behavior modification as an alternative to pharmacotherapy was generally high. A large majority of these caregivers (85%) expressed dissatisfaction with their training concerning psychotropic drugs. Finally, data were presented on drug topics about which respondents wanted to learn more and about changes they wished to see instated in their facilities. Our principal conclusion was that these data indicate a need for more education on a variety of social, pharmacological, and behavioral issues as they relate to medication use.     

Left ventricular regional function in patients with dilated cardiomyopathy (computerized echocardiographic data)

Computerized echography was used to assess left-ventricular dysfunction in 40 patients with dilatation cardiomyopathy (DCM). The so-called "floating" system was shown to be the most acceptable model for the correction of DCM-associated superposition. An original system was used for segment division by two- and four-chamber projections. Total left-ventricular hypokinesia and a significant reduction of the total ejection fraction (32.5 +/- 1.9%) were demonstrated.     

Preoperative transhepatic biliary decompression in pancreatic and periampullary cancer

Pancreatic resection for pancreatic and periampullary cancer between 1969 and 1975 at The Ohio State University Hospitals had an associated operative mortality rate of 30% and a morbidity rate of 80%. Transhepatic biliary decompression (THD) has been accepted as a method of preoperative risk reduction in the deeply jaundiced patient and an alternative to surgical biliary decompression. The use of preoperative THD in pancreatic and periampullary cancer was examined. Of 44 patients with bilirubin greater than 10 mg/100 ml, 17 had radical resection (THD=7, no THD=10), and 27 had palliative operation (THD=17, no THD=10). Preoperative serum bilirubin in the THD group was 7.3±1.0 compared to 16.3 ±1.5 in the no THD group (p < 0.05). Operative morbidity rate was: radical surgery: THD (40%), no THD (70%); palliative surgery: THD (18%), no THD (20%). Operative mortality rate was: radical surgery: THD (28%), no THD (60%); palliative surgery: THD (6%), no THD (0%). Catheter-related complications were minimal. Preoperative THD tends to reduce the risk of curative resection for pancreatic and periampullary cancer, but does not alter the outcome of palliative surgery. Long-term THD may be an alternative if palliative surgical biliary decompression either fails or is not technically possible in the patient with unresectable cancer.

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Resumen Se ha agudizado el debate relativo al papel de la resección curativa en el tratamiento del carcinoma pancreático y periampular. Mucha de la discusión se deriva de la excesiva morbilidad y mortalidad de la pancreatoduodenectomía y de la pancreatectomía total. Las cifras sobrepasan el porcentaje de supervivencia a 5 anos en todas las series mayores, y en algunos reportes la mortalidad operatoria es igual o mayor que el porcentaje de pacientes que sobreviven un año.La resección pancreática para cáncer pancreático y periampular entre los años 1969 y 1975 en los Hospitales de la Universidad del Estado de Ohio estuvo asociada con una mortalidad de 30% y una morbilidad de 80%. La descompresión biliar transhepática (DBT) ha sido aceptada como un método de reducción preoperatoria del riesgo quirúrgico en los pacientes intensamente ictéricos y como una alternativa a la descompresión biliar quirúrgica. El uso de la DBT preoperatoria en el cancer pancreático y periampular fué analizado. De 44 pacientes con bilirrubina mayor de 10 mg/100 ml, 17 fueron sometidos a resección radical (DBT = 7, no DBT = 10), y 27 tuvieron una operación paliativa (DBT = 17, no DBT = 10). La bilirrubina sérica en el grupo con DBT fué de 7.3±1.0, comparada con 16.3±1.5 en el grupo sin DBT (p < 0.05). La siguiente fué la morbilidad operatoria: cirugía radical: DBT 40%, no DBT 70%; cirugía paliativa: DBT 18%, no DBT 20%. La siguiente fué la mortalidad operatoria: cirugía radical: DPT 28%, no DPT 60%; cirugía paliativa: DBT 6%, no DBT 0. La DBT preoperatoria tiende a reducir el riesgo de la resección curativa para cáncer pancreático y periampular, pero no modiflca el resultado de la cirugía paliativa. La DBT prolongada puede ser una alternativa si la descompresión biliar quirúrgica falla o no es técnicamente posible en el paciente con cáncer no resecable.

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Résumé La résection pancréatique pour cancer périampullaire ou pour cancer du pancréas entre 1969 et 1975 à Ohio State University Hospital accuse une mortalité opératoire de 30% et une morbidité de 80%. Le drainage biliaire transhépatique (transhepatic biliary decompression: T.H.D.), en présence de ces résultats, a été employé à titre pré-opératoire pour diminuer les risques de l'intervention chez les malades très ictériques et comme alternative au drainage biliaire chirurgical.Chez 44 malades qui présentaient un taux de bilirubine supérieur à 10 mg/dl, 17 ont subi une exérèse (7 après drainage transhépatique, 10 sans drainage transhépatique), 27 ont été traités par une intervention palliative (17 après drainage, 10 sans drainage). Le taux de bilirubine pré-opératoire fut ramené à 7.3±10 chez les malades drainés alors qu'il atteignait 16.3± 1.5 chez les malades qui n'avaient pas subi de drainage préalable.La morbidité opératoire fut en cas de chirurgie radicale de 40% après drainage et de 70% en l'absence de drainage; en cas de chirurgie palliative elle fut de 18% après drainage et de 20% en l'absence de drainage. La mortalité opératoire fut en cas de chirurgie radicale de 28% après drainage et de 60% en l'absence de drainage; en cas de chirurgie palliative elle fut de 6% après drainage et de 0% en l'absence de drainage. Les complications du drainage sont très rares. En un mot le drainage biliaire pré-opératoire réduit les risques de l'exérèse des cancers pancréatiques et des cancers périampullaire mais elle est sans influence en cas d'intervention palliative. Le drainage biliaire transhépatique prolongé offre une alternative au drainage chirurgical lorsque celui-ci échoue ou quand le cancer ne peut être réséqué.

     

Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial

BackgroundThe use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.InterventionPatients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.Outcome measurements and statistical analysisThe secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.Results and limitationsFifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.ConclusionsThe atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.Patient summaryPatients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.     

Risk Factors and Effect of Acute Kidney Injury on Outcomes Following Total Hip and Knee Arthroplasty

BackgroundDevelopment of acute kidney injury (AKI) following primary total joint arthroplasty (TJA) is a potentially avoidable complication associated with negative outcomes including discharge to facilities and mortality. Few studies have identified modifiable risk factors or strategies that the surgeon may use to reduce this risk.MethodsWe identified all patients undergoing primary TJA at a single hospital from 2005 to 2017, and collected patient demographics, comorbidities, short-term outcomes, as well as perioperative laboratory results. We defined AKI as an increase in creatinine levels by 50% or 0.3 points. We compared demographics, comorbidities, and outcomes between patients who developed AKI and those who did not. Multivariate regressions identified the independent effect of AKI on outcomes. A stochastic gradient boosting model was constructed to predict AKI.ResultsIn total, 814 (3.9%) of 20,800 patients developed AKI. AKI independently increased length of stay by 0.26 days (95% confidence interval [CI] 0.14-0.38, P < .001), in-hospital complication risk (odds ratio = 1.73, 95% CI 1.45-2.07, P < .001), and discharge to facility risk (odds ratio = 1.26, 95% CI 1.05-1.53, P = .012). Forty-one predictive variables were included in the predictive model, with important potentially modifiable variables including body mass index, perioperative hemoglobin levels, surgery duration, and operative fluids administered. The final predictive model demonstrated excellent performance with a c-statistic of 0.967.ConclusionOur results confirm that AKI has adverse effects on outcome metrics including length of stay, discharge, and complications. Although many risk factors are nonmodifiable, maintaining adequate renal perfusion through optimizing preoperative hemoglobin, sufficient fluid resuscitation, and reducing blood loss, such as through the use of tranexamic acid, may aid in mitigating this risk.     

Relationship of airborne microorganisms with the lung function and leucocyte levels of workers with a history of humidifier fever

An influenza-like illness appeared recently among workers in a plant processing synthetic yarn. A humidifier, a cold-water spraying system, was the suspected cause. Lung function changes over the day and week and changes in blood leucocytes were studied among the workers from the suspected department and two reference populations. Exposure to colony-forming units of bacteria and fungi and to endotoxins was also monitored. The workers from the suspected department had statistically significantly lower lung functions on the first workday of the week than the referents. Their blood leucocytes were also raised statistically significantly. The exposure to fungi, bacteria, and endotoxins differed significantly between the various departments, but the measured levels were low. It was concluded that the observed effects were suggestive of a "Monday morning fever" type of reaction and that adverse effects occurred at exposure levels lower than those found to date in the literature.     

Cardioprotection by beta-blockers: molecular and structural aspects in experimental hypertension

This paper deals with some changes at the cardiac and aortic levels observed in normotensive rats and in hypertensive rats and turkeys by using two different beta-blockers, namely propranolol and oxprenolol. Chronic treatment with propranolol induced in the heart of normotensive rats a shift in the ventricular myosin pattern toward the "slow" V2 and V3 isoforms which are characterized by a reduced oxygen consumption. Oxprenolol treatment did not modify the blood pressure levels in the renal hypertensive rats nor in the spontaneously hypertensive turkeys. Nevertheless, in both experimental models a substantial modification of the media and intima, respectively, took place. In untreated hypertensive and normal rats the thickness of the aortic media was significantly higher than that of the treated ones, therefore suggesting a direct effect of oxprenolol on the smooth muscle cells of the aortic media. In the spontaneously hypertensive turkeys the atherosclerotic plaques appeared to be more frequent and thicker than those found in the oxprenolol-treated animals. These two experiments demonstrate that beta-blockers can prevent the development of hypertrophy of the media and decrease both the incidence and severity of intimal proliferations independently of blood pressure control. It therefore appears that the well-known myocardial protective effect played by beta-blockers, which mainly consists of a reduced myocardial oxygen consumption, is certainly obtained by reducing blood pressure and heart rate but also by changing the contractile protein pattern. In addition, an indirect myocardial protective effect could be exerted by beta-blockers at the vascular level by preventing medial hypertrophy and the development of atherosclerosis.     

Nonrandom secondary chromosome-aberrations in liposarcomas with t(12, 16)

Ten liposarcomas were analyzed cytogenetically after short-term culturing. Eight tumors had a t(12;16) (q13;p11) and two tumors had complex translocations involving chromosomes 7, 12, and 16 and 2, 9, 12, 16 and 20, respectively. Among the secondary aberrations seen in five tumors, +8 was found in two tumors and i(7)(q10) in four tumors. Trisomy 8 has previously been described as a nonrandom secondary aberration in myxoid liposarcoma, but i(7q) has only been reported in a single case before. All recurrent chromosome aberrations reported in liposarcomas with recombination between 12q13 and 16p11 (42 cases) were surveyed and compared with their frequencies in liposarcomas without this recombination (33 cases). Trisomy 5 and 8 were found in both tumor groups, whereas +19, t(3;15)(p23;q15), del(6)(q21), i(7q), and rearrangements of 1p11 and 2q35 were found exclusively in tumors with 12q13 and 16p11 aberrations.