Falls in older adults with cancer: an updated systematic review of prevalence, injurious falls, and impact on cancer treatment.

PURPOSE: This update of our 2016 systematic review answers the following questions: (1) How often do older adults with cancer fall? (2) What are the predictors for falls? (3) What are the rates and predictors of injurious falls? (4) What are the circumstances and outcomes of falls? (5) How do falls in older patients affect subsequent cancer treatment? and a new research question, (6) Which fall reduction interventions are efficacious in this population? METHODS: MEDLINE, PubMed, CINAHL, and Embase were searched (September 2015-January 25, 2019). Eligible studies included clinical trials and cohort, case-control, and cross-sectional studies published in English in which the sample (or subgroup) included adults aged ≥ 60, with cancer, in whom falls were examined as an outcome. RESULTS: A total of 2521 titles were reviewed, 67 full-text articles were screened for eligibility, and 30 new studies were identified. The majority involved the outpatient setting (n = 19) utilizing cross-sectional method (n = 18). Sample size ranged from 21 to 17,958. Fall rates ranged from 1.52 to 3.41% per 1000 patient days (inpatient setting) and from 39%/24 months to 64%/12 months (outpatient setting). One out of the 6 research questions contributed to a new finding: one study reported that 1 in 20 older patients experienced impact on cancer treatment due to falls. No consistent predictors for falls/fall injuries and no studies on fall reduction interventions in the geriatric oncology setting were identified. CONCLUSION: This updated review highlights a new gap in knowledge pertaining to interventions to prevent falls. Additionally, new knowledge also emerged in terms of impact of falls on cancer treatment; however, further research may increase generalizability. Falls and fall-related injuries are common in older adults with cancer and may affect subsequent cancer treatment. Further studies on predictors of falls, subsequent impacts, and fall reduction in the oncology setting are warranted.

Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy.

In both human and murine systems, we have developed an adoptive cellular therapy platform against medulloblastoma and glioblastoma that uses dendritic cells pulsed with a tumor RNA transcriptome to expand polyclonal tumor-reactive T cells against a plurality of antigens within heterogeneous brain tumors. We demonstrate that peripheral TCR Vß repertoire analysis after adoptive cellular therapy reveals that effective response to adoptive cellular therapy is concordant with massive in vivo expansion and persistence of tumor-specific T cell clones within the peripheral blood. In preclinical models of medulloblastoma and glioblastoma, and in a patient with relapsed medulloblastoma receiving adoptive cellular therapy, an early and massive expansion of tumor-reactive lymphocytes, coupled with prolonged persistence in the peripheral blood, is observed during effective therapeutic response to immunotherapy treatment.

Comparison of Frailty Scores in Newly Diagnosed Patients with Multiple Myeloma: A Review.

Multiple myeloma is a malignant plasma cell disease, which typically affects older patients, with a median age at diagnosis of 70 years. The challenge in treating older patients is to accurately identify 'fit' patients that can tolerate more intensive treatment to maximize disease control, while simultaneously identifying vulnerable or 'frail' patients who may develop toxicity with significant morbidity and mortality, requiring different treatment options or dose modification. Multiple frailty scores have been devised for multiple myeloma over the years in newly-diagnosed patients. This paper gives an overview of the three common frailty measurements: the International Myeloma Working Group Frailty Score, Mayo Clinic Frailty Score and the Revised Myeloma Co-Morbidity Index. We will summarize the derivation, validation, usability and applicability of these scores in different clinical settings, emphasizing the main strengths and limitations for each index score. We will also highlight future directions in the operationalization of frailty in multiple myeloma.

Electroencephalography and delirium in the postoperative period.

Delirium commonly manifests in the postoperative period as a clinical syndrome resulting from acute brain dysfunction or encephalopathy. Delirium is characterized by acute and often fluctuating changes in attention and cognition. Emergence delirium typically presents and resolves within minutes to hours after termination of general anaesthesia. Postoperative delirium hours to days after an invasive procedure can herald poor outcomes. Easily recognized when patients are hyperactive or agitated, delirium often evades diagnosis as it most frequently presents with hypoactivity and somnolence. EEG offers objective measurements to complement clinical assessment of this complex fluctuating disorder. Although EEG features of delirium in the postoperative period remain incompletely characterized, a shift of EEG power into low frequencies is a typical finding shared among encephalopathies that manifest with delirium. In aggregate, existing data suggest that serial or continuous EEG in the postoperative period facilitates monitoring of delirium development and severity and assists in detecting epileptic aetiologies. Future studies are needed to clarify the precise EEG features that can reliably predict or diagnose delirium in the postoperative period, and to provide mechanistic insights into this pathologically diverse neurological disorder.

Review of perioperative falls.

Falls are a known public health problem, and there is increasing recognition of the importance of perioperative falls for risk prediction and quality assessment. Our objective was to review existing literature regarding the occurrence, injuries, and risk factors of preoperative and postoperative falls. A systematized search of PubMed entries between 1947 and November 2015 produced 24 articles that met inclusion criteria. Most studied orthopaedic surgery patients older than 65 yr. Four were rated 'good' quality. Interrater reliability for the quality assessment was moderate (κ = 0.77). In the 3-12 months before surgery, the proportion of preoperative patients who fell ranged from 24 to 48%. Injuries were common (70%). The rate of postoperative falls ranged from 0.8 to 16.3 per 1000 person-days, with a gradual decline in the months after surgery. Injuries from postoperative falls occurred in 10-70% of fallers, and 5-20% experienced a severe injury. Risk factors were not well studied. Prospective studies reported a higher percentage of falls and fall-related injuries than retrospective studies, suggesting that there may be underdetection of falls and injuries with retrospective studies. Perioperative falls were more common than falls reported in the general community, even up to 12 months after surgery. Surgery-related falls may therefore occur beyond the hospitalization period. Future studies should use a prospective design, validated definitions, and broader populations to study perioperative falls. In particular, investigations of risk factors and follow-up after hospitalization are needed. REGISTRY NUMBER: PROSPERO registration number CRD42015029971.

Protocol for the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) study: a pragmatic, randomised clinical trial.

INTRODUCTION: Postoperative delirium, arbitrarily defined as occurring within 5 days of surgery, affects up to 50% of patients older than 60 after a major operation. This geriatric syndrome is associated with longer intensive care unit and hospital stay, readmission, persistent cognitive deterioration and mortality. No effective preventive methods have been identified, but preliminary evidence suggests that EEG monitoring during general anaesthesia, by facilitating reduced anaesthetic exposure and EEG suppression, might decrease incident postoperative delirium. This study hypothesises that EEG-guidance of anaesthetic administration prevents postoperative delirium and downstream sequelae, including falls and decreased quality of life. METHODS AND ANALYSIS: This is a 1232 patient, block-randomised, double-blinded, comparative effectiveness trial. Patients older than 60, undergoing volatile agent-based general anaesthesia for major surgery, are eligible. Patients are randomised to 1 of 2 anaesthetic approaches. One group receives general anaesthesia with clinicians blinded to EEG monitoring. The other group receives EEG-guidance of anaesthetic agent administration. The outcomes of postoperative delirium (≤5 days), falls at 1 and 12 months and health-related quality of life at 1 and 12 months will be compared between groups. Postoperative delirium is assessed with the confusion assessment method, falls with ProFaNE consensus questions and quality of life with the Veteran's RAND 12-item Health Survey. The intention-to-treat principle will be followed for all analyses. Differences between groups will be presented with 95% CIs and will be considered statistically significant at a two-sided p<0.05. ETHICS AND DISSEMINATION: Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) is approved by the ethics board at Washington University. Recruitment began in January 2015. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. TRIAL REGISTRATION NUMBER: NCT02241655; Pre-results.

High-dose therapy and autologous stem cell transplant in older adults with multiple myeloma.

Randomized trials showing that high-dose therapy with autologous stem cell transplant (ASCT) improved the overall survival (OS) in multiple myeloma (MM) excluded patients over age 65. To compare the outcomes of older adults with MM who underwent ASCT with non-transplant strategies, we identified 146 patients aged 65-77 with newly diagnosed MM seen in the Washington University School of Medicine from 2000 to 2010. Survival among patients who did (N=62) versus did not (N=84) undergo ASCT was compared using Cox proportional hazards modeling, controlling for comorbidities, Eastern Cooperative Oncology Group performance status (PS) and the propensity to undergo ASCT. Median age was 68 years (range 65-77). PS and comorbidities did not differ significantly between those who did versus those who did not undergo ASCT. Median OS was significantly longer in patients who underwent ASCT than in those who did not (median 56.0 months (95% confidence intervals (CIs) 49.1-65.4) versus 33.1 months (24.3-43.1), P=0.004). Adjusting for PS, comorbidities, Durie-Salmon stage and the propensity to undergo ASCT, ASCT was associated with superior OS (HR for mortality 0.52 (95% CI 0.30-0.91), P=0.02). In a cohort of older adults with MM, undergoing ASCT was associated with a nearly 50% lower mortality, after controlling for PS, comorbidities, stage and the propensity to undergo ASCT.

An anti-gp41 human monoclonal antibody that enhances HIV-1 infection in the absence of complement.

B lymphocytes from tonsillar tissue of an asymptomatic HIV-1-seropositive subject were transformed with Epstein-Barr virus (EBV) and tested for the production of HIV-1-specific antibodies by ELISA, using purified HIV-1SF2.2F11, a monoclonal antibody derived from a transformed line, is of the IgG1 subclass and recognizes an epitope in the conserved region of the envelope transmembrane glycoprotein gp41, which is expressed on the surface of HIV-infected T cells. The antibody does not mediate the lysis of infected T cells in antibody-dependent cellular cytotoxicity (ADCC) assays and does not neutralize the infectivity of HIV-1SF2 or the homologous isolate HIV-1TT2.2F11 appears to be the first anti-gp41 human monoclonal antibody that enhances the infectivity of an HIV-1 strain (i.e., SF128A) in the absence of complement.

Deep neck infections in patients at risk for acquired immunodeficiency syndrome.

The acquired immunodeficiency syndrome epidemic has introduced an increasing population of immune-compromised patients susceptible to infections by unusual pathogens. To evaluate the role of traditional antibiotic therapy for deep neck infections in high-risk patients, we reviewed the records of 73 patients with deep neck infections. Forty-six had or were at risk for acquired immunodeficiency syndrome, and nine were diabetics. Staphylococcal infections were more common in the at-risk group, and 24% of staphylococcal isolates in intravenous drug abusers were methicillin-sodium resistant. In addition, Klebsiella was isolated in two of nine diabetic patients. No other clinical differences were noted, and no unusual organisms were isolated from any other patients. Although traditional antibiotic therapy is appropriate for deep neck infections in patients at risk for acquired immunodeficiency syndrome, vancomycin hydrochloride should be considered when staphylococcal infections are suspected in intravenous drug abusers. Since diabetics appear to be susceptible to infections by gram-negative rods, broader antibiotic coverage must be considered in this population.

Evaluation of the orbital floor in zygoma fractures.

Displaced fractures of the zygoma require reduction to prevent malunion. The indications for concomitant orbital floor exploration are controversial. In a retrospective review, the preoperative clinical findings, roentgenographic findings, and mode of injury in 106 patients with zygoma fractures who had their orbital floors explored was compared with surgical findings. The finding of preoperative diplopia was correlated with a surgically significant floor defect. The finding of trismus correlated with the absence of a significant defect. No other clinical or roentgenographic finding was correlated to a significant degree with the presence or absence of a significant defect.

Spontaneous tonsillar hemorrhage.

Spontaneous tonsillar hemorrhage (STH) of non-iatrogenic causes occurs most frequently from infection. Infection can lead to erosion into a major vessel, such as the carotid artery or a smaller peripheral tonsil vessel. Whereas fatal erosion into a major vessel from a deep neck abscess was relatively common in the past, it is rare since the advent of antibiotics. Spontaneous tonsillar hemorrhage, when it does occur, appears to occur most commonly in a peripheral tonsil vessel from bacterial tonsillitis. Medical records of 860 patients with conditions considered to be susceptible to STH were reviewed. Ten cases of STH were identified. All were from peripheral tonsil vessel hemorrhage; none was secondary to major vessel erosion. Bacterial tonsillitis was the most common cause of STH and occurred in 8 of 10 cases. This condition accounted for an incidence of STH in tonsillitis of 1.1%. A history of chronic tonsillitis appeared to predispose a patient to STH. Other causes of STH were infectious mononucleosis and neoplasm. Seven of the ten peripheral STHs presented with bleeding from an obvious venous source. The other three patients had significant hemorrhages which led to arteriography. Arteriograms are indicated in patients with clinical features suggesting possible major vessel erosion or in those patients where significant bleeding is not from an obvious peripheral source. A peripheral STH can be successfully managed with local intervention and tonsillectomy.

Lateral cervical cyst containing gastric epithelium.

A lateral cervical cyst, presumably of branchial origin, was found to contain gastric epithelium. This is an extremely rare condition and, to our knowledge, represents the first such report in a branchial cyst. The literature is reviewed and speculations are made with respect to the embryologic and clinical implications of this anomaly.

Pulmonary edema and acute upper airway obstruction.

Pulmonary edema following the relief of acute upper airway obstruction is unusual and unpredictable. The cause is usually attributed to pulmonary and hemodynamic changes resulting from high negative intrathoracic pressures during obstructed respiration. The incidence of this problem is not known. Why pulmonary edema develops in only certain patients is also unclear. We reviewed the records of 27 consecutive adult patients admitted and treated for acute upper airway obstruction. Three of 27 (11%) developed pulmonary edema. Age, sex, diagnosis, duration of obstruction, history of cardiopulmonary disease, and perioperative fluid administration were evaluated. No differences were noted between those who did and those who did not develop pulmonary edema. Pulmonary edema following acute upper airway obstruction appears to be more common than is generally appreciated, however, no specific factors seem related to its occurrence.

Radiologic evaluation of irradiated cartilage grafts on the facial skeleton of sheep.

Augmentation mentoplasty is a commonly performed procedure for correction of retrognathia and microgenia. Implantable Silastic prostheses have become the mainstay of therapy, but have some disadvantages. One of the most important complications is erosion of the underlying mandible. An attempt was made to produce an experimental animal model to test the efficacy of irradiated costochondral cartilage in this regard. In order to prevent a biological material from eroding the underlying bone, the irradiated sheep cartilage grafts were placed subperiosteally, deep to a pair of large muscles of facial expression in five Suffolk sheep. Irradiated cartilage was used as the test material and merthiolate-treated cartilage as the control. Only 1 of the 20 grafts showed any absorption after 1 year, and this was only 1 mm in depth. Because of the meager amount of absorption of irradiated cartilage grafts, the ease with which they can be carved, and their ready availability, they would appear to be ideal implants for chin augmentation.