Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

CLINICO-EPIDEMIOLOGICAL ALGORITHM FOR PREDICTING SYSTEMIC ARTERIAL HYPERTENSION AT HIGH ALTITUDE THROUGH MATHEMATICAL MODELLING

A population based hybrid design combining element of cohort and cross-sectional approach was used to develop a simple clinical algorithm to predict individual probability of developing hypertension (systolic BP > 140 mm Hg and/or diastolic BP > 90 mmHg). 3615 soldiers initially normotensive at the time of induction into high altitude, were studied by systematic random sampling. Multiple logistic regression analysis showed a high significant association between hypertension and age, body mass index (BMI), tobacco smoking and alcohol consumption. Using the constant/coefficient values obtained from the logistic model and the receiver operating characteristics (ROC) curve analysis, the following predictive rule was developed – To the age in years, add (BMIx 3.86); also add 5.53 if he is a smoker; and add 19.81 if he consumes alcohol. If the total exceeds 142, the individual is at high risk of developing hypertension. This algorithm carries a sensitivity of 68.2% and specificity of 78.5%.KEY WORDS: Hypertension, High altitude     

The natural history of functional morbidity in hospitalized older patients

This study provides data on changes in the functional status of older patients that are associated with acute hospitalization. Seventy-one patients over the age of 74 admitted to the medical service of Stanford University Hospital between February and May 1987 received functional assessments covering seven domains: mobility, transfer, toileting, incontinence, feeding, grooming, and mental status. Assessments were obtained by report from the patient's caregiver (or the patient when he or she lived alone) for 2 weeks before admission; from the patient's nurse on day 2 of hospitalization and on the day before discharge; and again from the caregiver (or patient) 1 week after discharge. The sample had a mean age of 84, covered 37 Diagnostic Related Groups, and had a median length of stay of 8 days. Between baseline and day 2, statistically significant deteriorations occurred for the overall functional score and for the individual scores for mobility, transfer, toileting, feeding, and grooming. None of these scores improved significantly by discharge. In the case of mobility, 65% of the patients experienced a decline in score between baseline and day 2. Between day 2 and discharge, 67% showed no improvement, and another 10% deteriorated further. These data suggest that older patients may experience a burden of new and worsened functional impairment during hospitalization that improves at a much slower rate than the acute illness. An awareness of delayed functional recovery should influence discharge planning for older patients. Greater efforts to prevent functional decline in the hospitalized older patient may be warranted.     

Medicare reimbursement for geriatric assessment: report of the American Geriatrics Society Ad Hoc Committee on Geriatrics Assessment

This ad hoc committee report from the American Geriatrics Society proposes the prompt initiation of Medicare reimbursement for geriatric assessment (GA) services (also termed comprehensive geriatric assessment or geriatric evaluation and management services). Despite an extensive body of literature documenting the effectiveness of GA for improving health care outcomes in many settings for identifiable groups of frail elderly patients, no explicit Medicare reimbursement mechanisms currently exist to cover GA services provided by either hospital or physician. We believe that new physician reimbursement codes specific for geriatric assessment should be established in the Current Procedural Technology (CPT-4) manual and that reimbursement for GA should be specifically provided under Part B of Medicare. Further, we believe that hospital reimbursement within the Medicare prospective payment system should be modified to encourage GA during inpatient stays for appropriate patients. This paper summarizes the background for these recommendations. It defines the major content of GA at three levels of intensity--screening, intermediate, and comprehensive. It describes the major sites for conducting GA--hospital, office, home, nursing home. Finally, it proposes criteria for targeting patients most likely to benefit from GA.     

Rapid review of virus risk communication interventions: Directions for COVID-19

ObjectiveIn response to COVID-19, we conducted a rapid review of risk communication interventions to mitigate risk from viruses to determine if such interventions are efficacious.MethodsWe searched for risk communication interventions in four databases: Medline, PsycInfo, the ProQuest Coronavirus Research Database, and CENTRAL. The search produced 1572 articles. Thirty-one articles were included in the final review.ResultsResults showed risk communication interventions can produce cognitive and behavior changes around viruses. Results were more consistently positive for interventions focused on HIV/AIDS as compared to influenza. There was no consistent best intervention approach when comparing peer health, audio/visual, and intensive multi-media interventions. Tailoring risk communication toward a target population, in comparison to not tailoring, was related to better outcomes.ConclusionThe results suggest that risk communication interventions can be efficacious at reducing risk from viruses. They also highlight the complexity of risk communication interventions. Additional research is needed to understand the mechanisms that lead risk communication to reduce risk from viruses.Practical valueResults support risk communication interventions to reduce risk from viruses.     

The main steps in the development of anticancer agents

The development of new anticancer agents is a long-term process, which involves the acquisition of new compounds, screening for antitumor activity, production and formulation, animal toxicology and finally, evaluation of toxicity and antitumor activity of the compound in man (Table I). In this paper, the main steps in the early development of new cytotoxic agents up to phase II clinical studies will be discussed. However, clinical phase III-IV trails, where the efficacy of the drug has been proven, should be dealt with separately.     

The upper GI safety and tolerability of oral alendronate at a dose of 70 milligrams once weekly: a placebo-controlled endoscopy study

OBJECTIVE: Alendronate (10 mg daily) has been shown in long term clinical trials to be an effective treatment for postmenopausal osteoporosis. A weekly dosing regimen of alendronate is preferred by both patients and physicians, as it has the potential to provide greater convenience and enhance compliance. In a 1-yr clinical trial, alendronate (70 mg once weekly) was equally efficacious and at least as well tolerated as the 10-mg daily dose in the treatment of postmenopausal osteoporosis, despite the higher unit dosage required. We conducted a randomized, double blind, placebo- and active-controlled endoscopy study to confirm the results of this clinical trial. We hypothesized that mean endoscopic gastric erosion scores would be similar in subjects receiving alendronate (70 mg once weekly) and those receiving a placebo. METHODS: Two hundred seventy-seven subjects (90 men and 187 women) were randomized to one of three treatment groups: 1) alendronate (70 mg once weekly) for 10 wk (N = 126), 2) placebo (once weekly) for 10 wk (N = 126), or 3) placebo (once weekly) for 10 wk followed by aspirin (650 mg q.i.d.) for the last week as the positive control (N = 25). Esophagogastroduodenoscopy was performed 5 to 7 days after the last dose of alendronate or matching placebo. RESULTS: The mean gastric erosion scores (Lanza scale) were similar in subjects given alendronate (70 mg once weekly) and those given a placebo (0.32 vs 0.35, respectively; 95% CI for difference = -0.22-0.16, p = 0.75), whereas scores in both groups were significantly lower than in those given aspirin (3.09; p < 0.001). Endoscopic gastroduodenal ulcers occurred in no alendronate (0%), two placebo (1.7%), and five aspirin (23.8%) subjects. The mean erosion scores in the esophagus and duodenum of alendronate and placebo subjects were also similar. The incidences of upper GI symptoms were similar in the alendronate and placebo subjects and did not suggest a relationship with endoscopic lesions. CONCLUSIONS: Alendronate (70 mg once weekly) was not associated with any increase in endoscopic lesions in the upper GI tract relative to a placebo.     

Pancreatic cancer circulating tumor cells: applications for personalized oncology

Introduction: Pancreatic cancer (PC) is a highly lethal disease, in part because of early metastasis, late diagnosis, and limited treatment options. Circulating tumor cells (CTCs) are cancer cells that have achieved the metastatic step of intravasation, and are thus a unique source of biomarkers with potential applications in the staging, prognostication, and treatment of PC.

Areas covered: This review describes the use of CTCs in PC, including isolation methods, the significance of CTC enumeration, and studies examining phenotypic and molecular characteristics of CTCs. We also speculate on future directions for PC CTC research such as single-cell analysis and CTC culture.

Expert commentary: CTCs represent a potential unique serial source of cancer tissue via a convenient and minimally invasive blood draw. Recent development of isolation methods that allow for the release of viable CTCs with unaltered molecular characteristics has set the stage for single-cell analysis and ex vivo culture. Although there is significant potential for CTCs as a biomarker to impact PC from diagnosis to therapy, there still remain a number of challenges to the routine implementation of CTCs in the clinical management of PC.     

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.