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Prognostic evaluation before operative extirpation and radiotherapy of solitary brain metastasis.

This is a retrospective study of 134 patients operated on for solitary brain metastasis at the University Hospital in Uppsala, Sweden between 1963 and 1982. All the patients underwent postoperative radiation therapy. A statistical evaluation of different prognostic factors was made in order to create a prognostic model, a so-called risk profile, to be used for future patients. The most important factors for the making of risk profiles were found to be the "histological diagnosis" followed by the "location" in the brain, then the "state on admission" and the "age" at admission in that declining order. All these variables separately and together, i.e., as risk profiles, were matched against the outcome during survival as Karnofsky's scores and against the length of survival time. The results are shown in a diagram giving the surgeon grounds for his decision-making for or against operation and also for pre-operative information.

Age Factors↗

5-year survival and clinical prognostic factors in progressive supratentorial diffuse "low-grade" astrocytoma: a retrospective analysis of 46 cases.

In order to study survival and identify prognostic factors in progressive supratentorial low grade astrocytoma, 46 cases of diffusely growing glioma (1982-1989), in which stereotactic biopsy revealed a diagnosis of astrocytoma grade II according to Kernohan, were evaluated. Only patients with definite tumour growth on consecutive CT scans were included. All patients received a full course of fractionated radiotherapy. All tumour biopsy specimens were re-evaluated according to both the Kernohan and Daumas-Duport grading systems. Follow-up for at least 5 years showed a median survival of 47.5 months (1 year 71%, 5 year 41%). In Cox' multivariate analysis 4 factors turned out to give the best fitting prognostic model for survival: age, duration of symptoms, pre-operative neurological examination and CT-contrast enhancement. Numerical scoring was performed by giving either 1 or 0 for: age > or < 40 years, symptom duration < or > 1 year, presence or absence of focal deficit, and presence or absence of CT-contrast enhancement. Combining these factors in a score ranging from 0-4 resulted in 3 distinct groups with respect to median survival (< 2:66.5 months, 2:40 months, > 2:10 months, P = 0.0015). Although 17 cases with Kernohan grade II were upgraded using Daumas-Duport criteria (13 grade III, 4 grade IV), these cases did not form a separate survival-group. Additional parameters are needed to assess prognosis by neuropathological means, as some "low-grade" tumours are less benign than others, giving rise to a variable natural history.

Adolescent↗

Studies of higher nervous activity in functional phychoses.

Psychiatric illnesses can be conceived of as experiments of nature, providing a variety of pathopsychological mechanisms which may elucidate normal psychological processes. Clinically the reactive psychoses are predominantly psychogenic reaction types. They present disturbances of higher nervous activity, similar to those of the neuroses. The unconditional reflex activity is practically as in normal controls, and the most outstanding finding was the large effect of psychodynamic complex structures. This is a physiological parallel to the clinical manifestations with great concern over experienced mental trauma. In the manic-depressive psychoses the most characteristic feature is a marked disturbance of unconditional reflex activity. This factor may be an important physiological mechanism underlying the more biological than psychodynamic reaction type and partly explain the changes of mood and associated interferences with sleep, body weight, sexual activity, aggression and other instinctual and vegetative functions. Schizophrenic psychoses also present changes of unconditional reflex activity, predominantly in the direction of inhibition of response. In addition there are severe dissociations within and between the three levels of unconditional reflexes and the two signaling systems. It is suggested that schizophrenia represents a functional maladaptation, which can be explained from the principles of autokinesis and schizokinesis established by Gantt in animal experiments. Prognostic models based on experimentally established impairment of performances were shown to predict long-term risks of schizophrenic defects just as well as models based on constellations of clinical symptoms. I would predict that psychophysiology and experimental psychology will become increasingly more important for establishing diagnosis and prognosis in the functional psychoses. The data of this article point toward a basis for a prophylactic psychiatry.

Animals↗

Admission of patients with severe and moderate traumatic brain injury to specialized ICU facilities: a search for triage criteria.

OBJECTIVE: To investigate whether triage for direct admission of patients with traumatic brain injury to a trauma center is facilitated by predicting the risk of potentially removable lesions or raised intracranial pressure (ICP). DESIGN AND SETTING: Cohort study in a level I university trauma center. PATIENTS AND PARTICIPANTS: A prospective cohort of primarily (n=200) and secondarily (n=75) referred patients with moderate or severe traumatic brain injury. MEASUREMENTS AND RESULTS: Predictive characteristics for the risk of surgically removable lesions and the risk of raised ICP (repeatedly > or = 20 mmHg) were identified and included in prognostic models. These models were validated internally with bootstrapping techniques and externally on a historic sample (n=205) regarding discriminative ability (AUC). Among the cohort patients, 67% had raised ICP and 54% had surgically removable lesions. Both outcomes occurred more frequently in patients secondarily referred, but the incidence in patients primarily referred was also high (62% and 33% respectively). No strong predictors of raised ICP were identified. Age and pupillary reactivity were significant predictors of surgically removable lesions. The models discriminated reasonably for surgically removable lesions (AUC=0.78 at development and AUC=0.67 at external validation) but not for raised ICP (AUC=0.59 at development and AUC=0.50 at external validation). CONCLUSIONS: It is difficult accurately to identify patients in need of specialized intensive care using baseline characteristics. The high incidence of both outcomes in patients primarily referred support direct admission of more and particularly older patients with severe or moderate brain trauma to level I trauma centers.

Adult↗

The influence of missing components of the Acute Physiology Score of APACHE III on the measurement of ICU performance.

OBJECTIVE: To determine the impact of missing Acute Physiology Score (APS) values on risk-adjusted mortality. DESIGN: Retrospective review of prospectively collected Acute Physiology and Chronic Health Evaluation (APACHE) III database. SETTING: The intensive care units (ICUs) of an academic medical center. PATIENTS: 38,411 patients admitted to ICU between October 1994 and December 2003. MEASUREMENTS AND RESULTS: Data were collected on ICU type, missing first ICU day APS values, predicted and observed hospital mortality, standardized mortality ratio (SMR), 95% confidence interval (CI), odds ratio (OR). The overall observed and predicted hospital mortality rates were 8.7% and 10.8%, respectively, with SMR of 0.806 (95% CI 0.779-0.834). Complete data were available in 829 (2.2%). Vital signs were missing in almost none and serum albumin and bilirubin in over 80% of the patients. The number of missing variables was higher in less sick and surgical ICU patients. Logistic regression analysis showed that the risk of dying in the hospital was significantly associated with the number of missing APS variables (OR 1.058, 95% CI 1.027-1.090) when adjusted for the severity of illness. The risk of death was also associated with the type of missing variables. CONCLUSIONS: Since missing APS values may lead to underestimation of the predicted mortality rates, the number and type of missing variables should be taken into consideration when assessing the performance of an ICU. Unless data collection is standardized, future prognostic models should use variables that are routinely measured in most critically ill patients without sacrificing statistical precision.

APACHE↗

Accuracy of a composite score using daily SAPS II and LOD scores for predicting hospital mortality in ICU patients hospitalized for more than 72 h.

UNLABELLED: In most databases used to build general severity scores the median duration of intensive care unit (ICU) stay is less than 3 days. Consequently, these scores are not the most appropriate tools for measuring prognosis in studies dealing with ICU patients hospitalized for more than 72 h. PURPOSE: To develop a new prognostic model based on a general severity score (SAPS II), an organ dysfunction score (LOD) and evolution of both scores during the first 3 days of ICU stay. DESIGN: Prospective multicenter study. SETTING: Twenty-eight intensive care units (ICUs) in France. PATIENTS: A training data-set was created with four ICUs during an 18-month period (893 patients). Seventy percent of the patients were medical (628) aged 66 years. The median SAPS II was 38. The ICU and hospital mortality rates were 22.7% and 30%, respectively. Forty-seven percent (420 patients) were transferred from hospital wards. In this population, the calibration (Hosmer-Lemeshow chi-square: 37.4, P = 0.001) and the discrimination [area under the ROC curves: 0.744 (95 % CI: 0.714-0.773)] of the original SAPS II were relatively poor. A validation data set was created with a random panel of 24 French ICUs during March 1999 (312 patients). MEASUREMENTS AND MAIN RESULTS: The LOD and SAPS II scores were calculated during the first (SAPS1, LOD1), second (SAPS2, LOD2), and third (SAPS3, LOD3) calendar days. The LOD and SAPS scores alterations were assigned the value "1" when scores increased with time and "0" otherwise. A multivariable logistic regression model was used to select variables measured during the first three calendar days, and independently associated with death. Selected variables were: SAPS II at admission [OR: 1.04 (95 % CI: 1.027-1.053) per point], LOD [OR: 1.16 (95 % CI: 1.085-1.253) per point], transfer from ward [OR: 1.74 (95 % CI: 1.25-2.42)], as well as SAPS3-SAPS2 alterations [OR: 1.516 (95 % CI: 1.04-2.22)], and LOD3-LOD2 alterations [OR: 2.00 (95 % CI: 1.29-3.11)]. The final model has good calibration and discrimination properties in the training data set [area under the ROC curve: 0.794 (95 % CI: 0.766-0.820), Hosmer-Lemeshow C statistic: 5.56, P = 0.7]. In the validation data set, the model maintained good accuracy [area under the ROC curve: 0.826 (95 % CI: 0.780-0.867), Hosmer-Lemeshow C statistic: 7.14, P = 0.5]. CONCLUSIONS: The new model using SAPS II and LOD and their evolution during the first calendar days has good discrimination and calibration properties. We propose its use for benchmarking and evaluating the over-risk of death associated with ICU-acquired nosocomial infections.

APACHE↗

Predicting creatinine clearance by a simple formula following live-donor kidney transplantation.

The outcome after live-donor kidney transplantation is influenced by many parameters. The aim of our study was to establish a multivariate prognostic model for calculating the recipient's creatinine clearance after transplantation. Basic immunological, donor-, recipient- and process-related variables were assessed in a series of 18 live-donor kidney transplant patients with an uncomplicated postoperative course. Multivariate analysis was carried out with automated forward and backward selection. The following four parameters were included in the predictive model: recipient age, recipient BMI, graft clearance and degree of relationship. The coefficient of determination (R(2)) was 0.67. It could be shown that a significant prediction of creatinine clearance after living related kidney transplantation can be made, based on simple variables. Therefore, this formula could help to detect early complications in the post-transplantation course if the recipient's creatinine clearance drops below the predicted result.

Adolescent↗

Is it time for a reassessment of prognostic features in B-cell chronic lymphocytic leukemia?

Prognostic assessment of B-cell chronic lymphocytic leukemia (CLL) patients is generally based on either Rai or Binet clinical staging systems. However, new biological parameters which reflect the clinical heterogeneity of disease are under investigation. Cellular and molecular features including tumor cell proliferation, immunophenotype, adhesion molecules expression and release, karyotypic abnormalities and biological findings of increased angiogenesis have been correlated with tumor mass and survival. It is not clear, however, whether the newly identified prognostic parameters will eventually replace clinical variables representative of tumor mass. More likely, biological parameters might be incorporated into clinico-prognostic models thus leading to the formulation of a clinico-biological system for CLL.

Humans↗

[Standardized documentation of patho-anatomic findings using ADT (Association of German Tumor Centers) tumor forms for malignancies of the mouth, jaw and face (version III)].

The documentation form for pathohistologic findings (version III) for tumors of the maxillofacial region is presented. It is part of the site-specific documentation of the German Association of Tumor Centers (ADT). Its handling is explained by instructions which are based on the ICD-O classification and the TNM system. The prognostic relevance of the standardized documentation has already been proven by various histomorphologic investigations concerning oral and oropharyngeal cancer. By means of a multicentric observational study the German Austrian Swiss co-operative group DOSAK will develop a new prognostic model for oral and oropharyngeal cancer.

Documentation↗

Integrated bulk and single-cell RNA sequencing reveals a prognostic neuro-mimicry signature in papillary thyroid carcinoma.

BACKGROUND: Cancer cells can acquire neuron-like characteristics ("neural mimicry") to promote progression. However, the role of specific ion channel genes in Papillary Thyroid Carcinoma (PTC) and their clinical significance remains unclear. METHODS: We included transcriptomic data from 521 PTC patients in the TCGA cohort. A neuron-specific gene set was used to screen for potential targets. We constructed a prognostic model using LASSO logistic regression. To verify the cellular origin of the signature, we performed single-cell RNA sequencing (scRNA-seq) analysis on the GSE184362 dataset. RESULTS: We established an 8-gene signature involving KCNN4, KCNN1, KCNT2, SNAP25, KCNK16, GABRG1, GABRG2, and GABRB2. The model demonstrated good predictive performance for lymph node metastasis, with an AUC of 0.721 (95% CI 0.677-0.765). Single-cell analysis of seven integrated tumor samples (N&#x2009;=&#x2009;65,744 cells) confirmed that GABRB2 was specifically enriched in malignant thyrocytes (EPCAM+/KRT18+) at 200-fold higher detection rates than immune cells (20.0% vs. 0.1%, P&#x2009;&#x2248;&#x2009;0), supporting tumor-intrinsic neural mimicry. High-risk patients showed immunosuppressive features with altered immune cell infiltration patterns. CONCLUSION: This study identifies a malignant cell-intrinsic signature for predicting PTC prognosis. Validated by single-cell data, our findings suggest that targeting ion channels may represent a potential therapeutic strategy for modulating neuro-immune interactions in thyroid cancer, pending experimental validation.

GABRB2↗

Prognostic factors for death from visceral leishmaniasis in Teresina, Brazil.

BACKGROUND: A possible strategy to reduce fatality rates of visceral leishmaniasis is to identify prognostic factors that can be easily assessed and used as an aid to clinical decision-making. PATIENTS AND METHODS: A case-control study was developed in Teresina, Brazil, in which cases were patients who died during treatment (n = 12) and controls (n = 78) comprised a random sample of patients who were alive when treatment was finished. RESULTS: Variables significantly associated with death were severe anemia, fever for more than 60 days, diarrhea and jaundice. The prognostic system had a sensitivity of 85.7% and a specificity of 92.5%. CONCLUSION: The prognostic model developed in this study had satisfactory performance and might be useful in developing countries, since it is simple and inexpensive. However, it is still preliminary and needs to be improved and validated using larger and more recent samples.

Adolescent↗

Natural history and prognostic variables in primary sclerosing cholangitis.

The clinical features at the time of presentation and the outcome in 126 patients with primary sclerosing cholangitis were studied to clarify the natural history and prognosis in symptomatic and asymptomatic individuals. The median age of the patients at the time of presentation was 36 years, 62% were male, and 16% were asymptomatic. The median follow-up from time of presentation was 5.8 years. There were more patients who had liver transplants (21%) than patients who died of liver-related disease (16%); the estimated median survival to these end points was 12 years. Cholangiocarcinoma was found in 8 patients and in 23% of those undergoing liver transplantation. Asymptomatic patients had milder disease than symptomatic patients, but in a univariate analysis the presence of symptoms was not prognostically significant. On multivariate analysis, the following independent prognostic factors were found: hepatomegaly, splenomegaly, serum alkaline phosphatase, histological stage, and age. These features were combined to produce a prognostic model that should be valuable in the stratification of patients in clinical trials and in the timing of liver transplantation, particularly in those patients seen soon after presentation.

Adenoma, Bile Duct↗

Factors influencing outcome following radio-chemotherapy for oesophageal cancer. The Trans Tasman Radiation Oncology Group (TROG)

BACKGROUND AND PURPOSES: To define new directions, the Trans Tasman Radiation Oncology Group (TROG) has conducted a detailed analysis of its unrandomised experience with radio-chemotherapy in oesophageal cancer. METHODS AND PATIENTS: Since 1984, 373 patients with oesophageal cancer have been treated on three prospective, but unrandomised, protocols involving radiation with concurrent cisplatin and infusional fluorouracil. Centres in Australia and New Zealand have contributed patients. Reasons for case selection have been examined in detail and prognostic models have been examined in the light of biases exposed. RESULTS: Cause specific survival in 92 patients treated pre-operatively with 35 Gy, infusional fluorouracil and cisplatin was 25.5 +/- 6.0% at 5 years and similar to the 5 year expectations of 169 patients treated with 60 Gy and two courses of the same chemotherapy (23.8 +/- 4.7%). Analysis of failure in these groups suggests that local relapse precedes the development of metastases and competes as a cause for ultimate failure. Although patients treated surgically were less likely to relapse locally, survival was no better because more developed metastases. Some of the 112 patients treated "palliatively" with 30-35 Gy concurrent with chemotherapy without surgery have become long-term survivors with 5 year survival figure in this group 7.7 +/- 3.4%. Apart from variables related to disease stage and performance status at presentation, tumour site emerged as a strong predictor of outcome. Prognosis worsens the nearer the tumour is to the stomach. In addition, indications of a radiation dose response relationship emerged. CONCLUSIONS: Concurrent radio-chemotherapy protocols can improve outcome in patients fit enough to tolerate these approaches. New strategies remain necessary, however.

Adenocarcinoma↗

In vitro suppression of DNA synthesis by a remission induction agent and its correlation with response in adult acute leukemia.

Fifty-three adult patients who presented with previously untreated acute leukemia had leukemic cells incubated in vitro with five doses of cytosine arabinoside (0.001-0.1 microgram/ml) and adriamycin (0.1-10 microgram/ml). Thymidine incorporation was measured in treated and untreated cells. Greater than 80% suppression of pretreatment thymidine incorporation after treatment with 0.004 micrograms/ml of cytosine arabinoside correlated with complete remission (CR) of the patient. A Mahalanobis' D2 score, which provides an index of the deviation of patient's in vitro drug response from the mean profile of responders, was calculated for each drug. Patients who had D2 values greater than 10 for Ara-C were less likely to respond to therapy. Patients with low D2s had rates of CR higher than predicted by the prognostic model employed at U.T.M. D. Anderson Hospital. However, unlike in our previous report, responders and non-responders were not clearly separable on the basis of the D2 value.

Adolescent↗

Genetic changes in breast cancer--consequences for therapy?

The knowledge of specific genetic changes and their biological consequences is critical to an understanding of the natural history of breast tumors and the development of rational means to prevent and treat them. A number of genetic changes have been identified in breast tumors. Some of these involve specific genetic loci that directly contribute to one or more attributes of transformation, i.e., dysregulated proliferation and invasion, while other changes confer genetic instability that increases the possibility of acquiring subsequent, specific genetic lesions relevant to tumorigenesis. Many of these changes have been correlated with an adverse prognosis and attempts to integrate these in comprehensive multifactorial prognostic models are in progress. Initial clinical trials have also demonstrated the 'proof of concept' of targeting specific genetic lesions for therapeutic purposes. In the not too distant future, we can envision the use of specific therapies for individual (or subgroups of) tumors based on the specific genetic changes that lead to their development, rather than the global approach of multiagent cytotoxic therapy that is in widespread use today.

Breast Neoplasms↗

Predicting mortality in adult burned patients: methodological aspects of the construction and validation of a composite ratio scale.

This article describes the methodology of construction and validation of a composite measurement scale (CMS) to predict the risk of death for burned patients, with severity of burn considered as a continuous phenomenon. Three large data sets of burned patients hospitalized in France were analyzed. Logistic regression was used to construct a prognostic model, based on age and initial evaluation of total body surface area burned. The resulting model appears to be a valid clinical tool for predicting the risk of death. In addition, the devised CMS has satisfactory content and construct validity and reliability, and provides a high measurement level (logistic ratio level). Moreover, its simplicity of use (the score is integer based) is appropriate for the daily activities of burn unit physicians, emergency medical technicians, and public health professionals.

Adult↗

Assessing the benefits of transplant services.

This chapter presents some methods for the assessment of transplant benefits, using the example of liver transplantation. An independent assessment of the benefits of medical technology is especially important for evaluation of the balance between the costs and benefits involved. To enable comparison with other health-care facilities, benefits are defined in terms of a combination of life-years gained and quality of life. The number of life-years gained can be calculated by comparing the survival expected with and without transplantation. Survival with transplantation is estimated on the basis of observed survival, acknowledging that the probability of survival may have changed over time, owing to changes in therapy and selection criteria. To estimate survival without transplantation, several techniques are available. Prognostic models, correcting for stage of disease, are often used. Pitfalls in the use of these models are discussed. The number of life-years gained can be corrected for quality of life by weighing survival with and without transplantation with an index representing quality of life. A method for the calculation of such an index is given. Finally, some cost estimates are presented and the results are discussed.

Cost-Benefit Analysis↗

An investigation of cut-points for primary breast cancer oestrogen and progesterone receptor assays.

Oestrogen and progesterone receptor (ER and PgR) assay values are frequently used in medical decision-making for breast cancer patients. We have proposed statistical standardization of receptor assay values to improve inter-laboratory comparability, and now report the use of standardized log units (SLU) to investigate the effects of ER and PgR cut-points on time to first recurrence outside the breast (DFS). Between 1980 and 1986, there were 678 primary breast cancer patients treated at the Henrietta Banting Breast Centre (HBBC). The effects of ER and PgR cut-points were examined with multivariate analyses considering the variables: age, tumour size, nodal status, weight and adjuvant treatment. We considered receptor assay cut-points ranging from - 1.0 to + 1.0 SLU (ER between 7 and 166 fmol/mg protein; PgR between 7 and 181 fmol/mg protein). PgR was included in the multivariate prognostic models more often than ER, although patients had a better prognosis with both larger ER and PgR values. There was no best cut-point for ER or PgR, and there was strong evidence that ER and PgR should be considered as continuous rather than dichotomous (negative, positive) variables. Patient prognosis should also be more comparable with SLU.

Breast Neoplasms↗