Real-world treatment sequencing and survival in previously treated advanced renal cell carcinoma patients receiving nivolumab monotherapy: a UK retrospective cohort study.

BACKGROUND: The CheckMate 025 trial established nivolumab monotherapy as one of the standards of care in previously treated advanced or metastatic renal cell carcinoma (aRCC). However, supporting real-world data is lacking. This study investigated characteristics, treatment sequences and clinical outcomes of patients who received nivolumab monotherapy for previously treated aRCC in the UK. METHODS: This was a retrospective cohort study of aRCC patients treated with nivolumab at second line or later (2L +) at 4 UK oncology centres. Eligible patients commenced nivolumab (index date) between 01 March 2016 and 30 June 2018 (index period). Study data were extracted from medical records using an electronic case report form. Data cut-off (end of follow-up) was 31 May 2019. RESULTS: In total, 151 patients were included with median follow-up of 15.2 months. Mean age was 66.9 years, male preponderance (72.2%), and mostly Eastern Cooperative Oncology Group performance status grade 0-1 (71.5%). Amongst 112 patients with a known International Metastatic RCC Database Consortium score, distribution between favourable, intermediate, and poor risk categories was 20.5%, 53.6%, and 25.9% respectively. The majority of patients (n = 109; 72.2%) received nivolumab at 2L, and these patients had a median overall survival (OS) of 23.0 months [95% confidence interval: 17.2, not reached]. All patients who received nivolumab at 2L had received TKIs at 1L. Amongst the 42 patients (27.8%) who received nivolumab in third line or later (3L +) the median OS was 12.4 months [95% CI: 8.8, 23.2]. The most common reasons for nivolumab discontinuation were disease progression (2L: 61.2%; 3L: 68.8%) and adverse events (2L: 34.7%; 3L: 28.1%). CONCLUSION: This study provides real-world evidence on the characteristics, treatment sequences, and outcomes of aRCC patients who received 2L + nivolumab monotherapy in the UK. Nivolumab-specific survival outcomes were similar to those achieved in the CheckMate 025 trial.

Low speech rate but high gesture rate during conversational interaction in people with Cornelia de Lange syndrome.

BACKGROUND: Cornelia de Lange syndrsome (CdLS) is a rare genetic syndrome with notable impaired expressive communication characterised by reduced spoken language. We examined gesture use to refine the description of expressive communication impairments in CdLS. METHODS: During conversations, we compared gesture use in people with CdLS to peers with Down syndrome (DS) matched for receptive language and adaptive ability, and typically developing (TD) individuals of similar chronological age. RESULTS: As anticipated the DS and CdLS groups used fewer words during conversation than TD peers (P < .001). However, the CdLS group used twice the number of gestures per 100 words compared with the DS and TD groups (P = .003). CONCLUSIONS: Individuals with CdLS have a significantly higher gesture rate than expected given their level of intellectual disability and chronological age. This result indicates the cause of reduced use of spoken language does not extend to all forms of expressive communication.

Temperature impacts Atlantic salmon's (Salmo salar) immunological response to infectious salmon anemia virus (ISAv).

Ocean temperatures continue to rise annually due to the ever-growing consequences of global climate change. These temperature changes can have an impact on the immunological robustness of cultured fish, especially cold-water species such as Atlantic salmon. The salmon farming industry already loses hundreds of millions of dollars each year to infectious and non-infectious diseases. One particularly important and WOAH reportable disease is infectious salmon anemia caused by the orthomyxovirus ISAv. Considering the changing environment, it is necessary to find ways to mitigate the effect of diseases on the industry. For this study, 20 Atlantic salmon families were housed in each of 38 different tanks at the AVC, with half of the fish being kept at 10 °C and half being kept at 20 °C. Donor Atlantic salmon IP- injected with a highly virulent ISAv isolate (HPR4; TCID50 of 1 × 105/mL) were added to each tank as the source of co-habitation infection. Both temperatures were sampled at onset of mortality in co-habited fish and at resolution of mortality. Family background and temperature significantly impacted ISAv load, as assessed by qPCR, time to mortality and overall mortality. Mortality was more acute at 20 °C, but overall mortality was higher at 10 °C. Based on percent mortality calculated over the course of the study, different families demonstrated different levels of survival. The three families that demonstrated the highest percent mortality, and the three families with the lowest percent mortality were then assessed for their antiviral responses using relative gene expression. Genes significantly upregulated between the unexposed fish and ISAv exposed fish included mx1, il4/13a, il12rb2, and trim25, and these were further impacted by temperature. Understanding how ISAv resistance is impacted by temperature can help identify seasonal risks of ISAv outbreaks as well as ideal responses to be targeted through immunopotentiation.

Inequity Analysis in Faculty Recognition Awards at a School of Medicine.

As part of developmental networks, sponsors help provide recognition and visibility opportunities to their faculty protégés. Recognition awards given to the School of Medicine (SOM) faculty are an important mechanism for acknowledging what is valued in academic medicine. Beyond their impact on individual careers, awards help define the culture and climate of an organization. The literature suggests inequities in recognition awards for women and racial/ethnic underrepresented minority faculty. The study's purpose was to examine the characteristics of the awardees relative to the SOM faculty in a minority-serving institution in a minority-majority state. In this observational cross-sectional study, 47 SOM faculty were recognized between 2000-2023 as Regents' Lecturers (9), Regents' Professors (20), Community Engagement Awardees (5), and Gold-headed Cane Awardees (13). SOM sought nominations which a search committee competitively reviewed. Award recipients were characterized by their department, rank, academic track, degree, country of origin, sex, and race/ethnicity, and were compared to all SOM faculty. Male faculty were more likely than women faculty to receive an award (p=0.04). Faculty with tenure, Ph.D. degree, or Professor rank were more likely to receive an award than their counterparts (p<0.001, all analyses). Faculty in basic and diagnostic specialties were more likely to receive an award than medical or surgical specialties (p<0.001). Although rates of awards for racial/ethnic URM faculty were about half that of non-URM faculty, this difference did not reach statistical significance (p=0.14). In addition to demonstrating sex-related inequity in awards, recognized faculty are traditionally associated with the scholarship of discovery compared to other models of scholarship or clinical activity. Sponsors should promote women, physicians, and clinician educators for recognition awards to advance their academic careers. SOM leaders need to examine award criteria and processes to ensure recognition of the diversity of talents and achievements that are critical to the future of academic medicine.

Chip fractures from the distal lateral trochlear ridge of the talus of a quarter horse gelding: a veterinary medicine clinical report.

An eighteen-month old quarter horse gelding was diagnosed with chip fractures from the distal lateral trochlear ridge of the talus. The horse presented with the symptom of persistent synovitis. The diagnosis was based on radiographic evidence. The horse was treated initially with arthroscopic surgery. He was given a non-steroidal anti-inflammatory agent, and a chondroprotective agent to prevent further damage to, and aid in the healing of, the damaged joint.

Comparative profile of tizanidine in the management of spasticity.

The therapeutic profile of a new antispastic drug cannot be defined solely on the basis of placebo-controlled studies. Its potential advantages must be evaluated in comparison with existing drugs. This review compares the efficacy and tolerability of tizanidine, a newer muscle relaxant, with that of baclofen and diazepam, the most widely used antispastic agents, for a variety of diagnoses and target symptoms associated with spasticity. More than 20 double-blind, comparative studies were conducted between 1977 and 1987. These included a total of 777 patients suffering from spasticity of various causes. The collected clinical data have been integrated into a combined analysis. Tizanidine emerges from this comparison as a valuable drug in the treatment of spasticity related to cerebral and spinal disorders.

Safety of estazolam. The United States clinical experience.

The safety profile of estazolam, a new triazolobenzodiazepine hypnotic medication, has been developed in 1,320 normal volunteers and patients with insomnia. No clinically significant effects of estazolam on vital signs or laboratory values were detected. Drug-specific adverse effects such as somnolence, dizziness, hypokinesia, and abnormal coordination occurred, but these are expected extensions of benzodiazepine pharmacologic activity. No consistent effects on psychomotor performance, including memory, were seen at the recommended hypnotic doses in insomniac subjects. These data, combined with the evidence for hypnotic activity, indicate that estazolam is a safe and effective treatment for insomnia.

Atherosclerosis of the left main coronary artery: 5 years results of surgical treatment.

Three hundred consecutive patients received coronary arterial bypass grafts as treatment for stenosis of the left main coronary artery. Ostial stenosis was more prevalent among women (P less than 0.001). Operative (hospital) mortality was 4 percent (12 of 300). Among 148 survivors who underwent recatheterization after a mean interval of 16.5 months, the graft patency rate was 88 percent. After a minimal follow-up period of 49 months and a mean interval of 69 months, 75 percent of the survivors were asymptomatic and 94 percent were employed or fully active. The actuarial 5 year survival rate was 88.2 percent. The presence of right coronary artery disease, abnormal preoperative ventricular function and incomplete revascularization adversely affected survival, but the differences did not reach statistical significance. Comparison of this long-term follow-up study with controlled and noncontrolled studies of nonsurgical treatment of obstructions of the left main coronary artery indicates that myocardial revascularization alleviates cardiac symptoms and increases life expectancy in patients with severe atherosclerosis of this artery.

Methylphenidate in treating poststroke depression.

The authors retrospectively studied the charts of 25 patients with poststroke depression who were treated with methylphenidate. The 13 patients (52%) who recovered completely from their depression did not differ significantly from the 12 nonresponders on demographic characteristics, location of cerebrovascular accident, and other variables. Mood usually improved within 48 hours; only 3 (12%) patients had side effects. Rapid response to treatment and lack of significant side effects indicate that methylphenidate may be a valuable treatment for poststroke depression.

Efficacy and side effects of methylphenidate for poststroke depression.

BACKGROUND: Depression after stroke impedes the rehabilitation process and causes additional suffering to patient and family. Few studies have systematically examined pharmacologic treatments of poststroke depression. In the present paper, the use of the stimulant methylphenidate is studied in a depressed, elderly stroke population. METHOD: Ten subjects (mean age = 73.2 years) meeting DSM-III-R criteria for major depression were followed-up during a 3-week efficacy and side effect trial involving methylphenidate. Subjects were selected from rehabilitation patients referred for psychiatric consultation. RESULTS: A total of 80% (8 of 10) of the subjects showed either a full or partial response as measured by Hamilton Rating Scale for Depression scores. The incidence of problematic side effects was low, and no subjects had to be discontinued from the study. CONCLUSION: Results of this methylphenidate trial for poststroke depression in elderly patients suggest that it is a safe and effective treatment for poststroke depression. Future studies are called for in which methylphenidate is compared with placebo controls and antidepressant medication.

Cannulation of the ascending aorta for cardiopulmonary bypass. Experience with 9,000 cases.

The Cleveland Clinic team has now accumulated experience with cannulation of the ascending aorta for arterial return in more than 9,000 patients. Since adoption of this technique, only one lethal dissection has occurred and other related complications have been minimal. Technique, surgical pitfalls, contraindications, and complications of ascending aortic cannulation are discussed in this communication.

Rupture of the posterior wall of the left ventricle after mitral valve replacement.

Rupture of the posterior wall of the left ventricle is an unusual but often lethal complication following mitral valve replacement (MVR). We have encountered it six times with a 100 per cent mortality rate in a series of 1,154 operations for MVR. Sites of rupture were located at the base of the resected papilary muscle or close to the artioventricular groove in the area adjacent to the resected posterior mitral leaflet. T stongly indicates the overzealous resection of the mitral leaflets and papillary muscle as an important eitiologic factor. Other possible etiologic factors are discussed and important pitfalls to be avoided during MVR are stressed.

Manual coronary endarterectomy. Clinical experience in 315 patients.

From July, 1970, to December, 1973, manual endarterectomies were performed on 330 coronary arteries in 315 patients. The procedures were performed on either an elective or nonelective basis. The over-all hospital mortality rate was 1.27 per cent. Postoperative myocardial infarction occurred in 4.8 per cent of these patients. Postoperative catheterization was performed on 186 endarterectomized arteries; the average time of postoperative catheterization was 13.1 months after surgery. The over-all patency rate was 76.3 per cent. This experience suggests that endarterectomy is a safe and useful adjunct to saphenous vein bypass grafting procedures when used in a restricted fashion as detailed in this presentation.

Clinical results of mechanical support of the failing left ventricle.

Six patients received mechanical support for a failing left ventricle after corrective cardiac operations. Despite intra-aortic balloon pumping and pharmacologic support, intractable failure persisted and cardiopulmonary bypass could not be withdrawn. The left ventricular assist device (LVAD) consists of a nonpulsatile centrifugal pump and two thromboresistant cannulas. Balloon counterpulsation added a pulsatile effect. LVAD support was continued for 72 to 168 hours and five patients were weaned from LVAD support. Two died of persistent low cardiac output within 3 days after pump removal, and a fourth died of multiple organ failure and pneumonia 8 weeks after LVAD removal. Autopsy studies in the first three patients showed myocardial necrosis greater than 50% of the left ventricular mass. Two patients survived after 72 and 74 hours of LVAD support. One patient is fully employed and active 27 months after a cardiac operation; the second is fully active 20 months after operation. Repeat cardiac catheterizations in both have shown all grafts patent and good ventricular function. These two long-term survivors justify the concept of LVAD support and its continued use in selected postoperative patients.

Late clinical and arteriographic results in 500 coronary artery reoperations.

The incidence of coronary artery reoperations averaged 2.7% from 1967 through 1979. In a mean interval of 51 months between operations, three-vessel disease increased from 24% to 63%, and 31% of these 500 consecutive patients lost previously normal left ventricular function. Three angiographic indication groups were identified: (1) progressive coronary atherosclerosis, 247 (51%); (2) graft failure, 147 (29%); and (3) a combination of progressive coronary atherosclerosis and graft failure, 96 (19%). Angina recurred earlier in patient with graft failure, mean 17 months compared with a mean of 37 months for the other groups. Twenty (4%) operative deaths occurred. The series is divided into 387 patients operated upon under normothermic anoxic arrest and 113 with systemic hypothermia and cold cardioplegia. In the cardioplegia group, perioperative myocardial infarction was 2.7% in comparison with 7.8% for patients with anoxic arrest (p = 0.055). The number of grafts per patient increased from 1.0 to 1.9 and blood usage decreased from 11 units to 2.7 units. After a mean follow-up of 42 months, angina was relieved or improved in 86%. Recatheterization of 104 patients after a mean interval of 19 months showed a 79% vein graft patency rate and a 97% mammary artery graft patency rate. Grafting performed for graft failure (47) yielded an 85% patency rate. Actuarial 5 year survival was 87.4% for those with progressive atherosclerosis, 89.4% for patients with graft failure, and 91.5% for the combined indication group. Clinical improvement, graft patency, and long-term survival are nearly equal among the indication groups. Palliation derived from these reoperations approaches that achieved after primary revascularization.

Bridge saphenous vein graft.

Single aorta-coronary artery vein grafts (bridge grafts) were constructed to two coronary branches with a side-to-side anastomosis in 250 patients. Most of these grafts were constructed between circumflex branches (96 grafts), circumflex and diagnol branches (47 grafts), and anterior descending and diagonol branches (79 grafts). The aim of the bridge graft is to decrease the number of anastomoses, decrease the operative time, and improve graft patency. The hospital mortality rate in this group of patients was 1.2 per cent, and the incidence of postoperative myocardial infarction was 3.6 per cent. One hundred ten patients were restudied after surgery; the average time of restudy was 1 year. Ninety-two grafts of 83.6 per cent had two anastomosis patent; 6 grafts (5.4 per cent) had one anastomosis patent; and in 12 grafts (10.9 per cent), both anastomoses were occluded. One hundred twenty-six associated grafts were studied all the same time; the patency rate was 84.1 per cent. From this experience, we believe the bridge graft is a useful procedure for bypassing the small coronary artery branches.

Reoperations for myocardial revascularization.

Reoperations solely for myocardial revascularization were performed in 219 consecutive patients (1967 to 1975). Indications were (1) graft failure, 46 (21 per cent); (2) progressive atherosclerosis, 42 (19 per cent); (3) incomplete revascularization, 39 (18 per cent); and (4) combinations, 92 (42 per cent). Primary operations included bypass grafts in 100 patients; mammary artery implants, 87; and combinations of direct and indirect procedures, 32. Reoperations performed were single bypass, 141 patients; double, 61; and triple or other coronary artery operations, 17. Eight patients died within 30 days of operation (3.7 per cent). Major postoperative complications included hepatitis, 24 (11 per cent); myocardial infarction, 19 (9 per cent); bleeding, 21 (10 per cent); and respiratory insufficiency, 12 (5 per cent). Follow-up for 202 long-term survivors was complete (mean 29 months). In patients who originally underwent direct revascularization, Class I or II (N.Y.H.A.) was attained in 35 of 43 (81 per cent) of those reoperated upon for primary graft failure, in 14 of 15 (93 per cent) of those with progressive atherosclerosis, and in 27 of 33 (82 per cent) of patients with combined indications. Arteriography was performed after the reoperation in 55 patients (mean interval 17 months), and 65 of 77 (84 per cent) grafts were patent. Nineteen of 22 grafts performed for primary graft failure were patent. We have made the following conclusions: (1) Reoperation for direct myocardial revascularization can be accomplished with low mortality rates although morbidity is high; (2) complete relief of symptoms was achieved in 65 per cent of survivors; (3) results in patients reoperated upon for graft failure alone were similar to results in those operated upon for progressive atherosclerosis or combined indications; and (4) high graft patency was found in secondary grafts constructed to arteries involved with primary graft failure.

Use of the dexamethasone suppression test with depressed and demented elderly.

Although some researchers have suggested that the dexamethasone suppression test (DST) may be useful in differentiating between major depression and dementia in the elderly, recent reports of abnormal DST results in nondepressed, demented elderly have questioned the validity of the test in this population. This study compared the frequency of abnormal DST results in three groups of elderly inpatients: depressed/not demented; demented/not depressed; and depressed and demented. Two geropsychiatrists independently evaluated 33 patients for symptoms of depression and/or dementia and then assigned each patient to one of the three groups. Subjects in the demented/not depressed group had a significantly larger proportion of abnormal DSTs (P less than .01), and the mean postdexamethasone, 4 PM blood cortisol level of the demented/not depressed group was significantly greater than the means of the other two groups (P less than .005). In this sample, the DST was more likely to identify dementia than depression. Until further investigations clarify the parameters of DST use in the elderly, the diagnosis of depression and dementia should continue to be determined by sensitive interpretation of clinical findings, history, and other diagnostic tests.