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Free triiodothyronine in sera of acutely ill general medical patients: a prognostic indicator?

We measured free triiodothyronine (FT3), thyrotropin (TSH), and C-reactive protein (CRP) in sera of 39 acutely ill medical patients who died within three months of admission and 39 age- and sex-matched control patients selected at random from a total of 294 acute medical admissions. Serum FT3 in nonsurvivors (1.91 +/- 1.51 pmol/L) was significantly lower than that in survivors (3.01 +/- 1.3 pmol/L, P less than 0.01) and the CRP in nonsurvivors (54.6 +/- 59.2 mg/L) was significantly higher than in survivors (43.6 +/- 59.5 mg/L, P less than 0.05). There was no difference in plasma TSH between the two groups. The estimated odds ratio relating death to a plasma FT3 value less than 1.0 pmol/L on admission was 17 (highly significant: P less than 0.001). We conclude that plasma FT3 may be a useful prognostic indicator in acutely ill patients.

Acute Disease↗

Mesocolic lymph node histology is an important prognostic indicator for patients with carcinoma of the sigmoid colon: an immunomorphologic study.

Histologic parameters which are thought to reflect either cell-mediated (T cell) or humoral (B cell) immune responses in lymph nodes have been studied in regional lymph nodes draining carcinoma of the sigmoid colon. Patients whose lymph nodes show morphological evidence of cell-mediated immunity, manifested either by an increased number of paracortical immunoblasts or sinus histiocytosis, survive significantly longer than those whose lymph nodes show no such changes. Patients whose lymph nodes show simultaneous paracortical activity and sinus histiocytosis have the best survival of all. Of this latter group, 11/13 (83 percent) are living without signs of recurrent tumor 5 or more years after surgery. Histologic parameters which suggest an antibody-mediated immune response (germinal center activity) were not an important prognostic indicator. The occurrence of favorable lymph node histology does not appear to significantly correlate with the modified Duke's classification. Rather, the favorable changes allow selection of a large proportion of those patients within the various Duke's categories who are destined to become long-term survivors.

Antibody Formation↗

Survival of patients with acute renal failure requiring dialysis after open heart surgery: early prognostic indicators.

We analyzed pre- and postoperative data from 36 consecutive patients, who developed acute renal failure requiring hemodialysis after open heart surgery, to determine which factors predicted survival. Seventeen patients (47%) survived. Age, sex, preoperative renal dysfunction, severity of underlying heart disease, perioperative myocardial infarction, cardiopulmonary bypass time, and oliguria did not influence outcome (by univariate analysis). However, the number and type of postoperative complications, before the first hemodialysis and 48 hours thereafter, were found to be significant predictors of outcome. Univariate as well as multivariate analysis showed that the highest mortality rate was associated with the presence of respiratory failure, central nervous system dysfunction, hypotension, and infection (48 hours after first hemodialysis). Thirty-three (92%) of the 36 patients were correctly classified as survivors or nonsurvivors based on the presence or absence of any one of three prognostic indicators (three or more complications before the first hemodialysis and persisting 48 hours later; hypotension before the first dialysis and persisting 48 hours later; or central nervous system dysfunction 48 hours after hemodialysis was initiated). We conclude that an assessment of prognosis can be made in such patients as early as 48 hours after the first hemodialysis based on the number and type of complications.

Acute Kidney Injury↗

The acoustic stapedial reflex as a prognostic indicator in sudden onset sensorineural hearing loss.

Forty consecutive patients with sudden onset sensorineural hearing loss treated similarly over a four-year period were studied retrospectively to determine a correlation between presence or absence of the acoustic stapedial reflex (ASR) and recovery of hearing. Six patients were dropped from the study because of incomplete data. There were 42 affected ears in the remaining 34 patients. The ASR was present in 28 (67%) of the 42 affected ears that had either full or partial recovery. The ASR was not present in 11 ears (26%) in which there was no recovery. The ASR was present in three ears (7%) in which there was no recovery. There was a statistically significant association (P < .001) between presence of the ASR and eventual full or partial recovery of hearing in this series. The ASR would have been an effective prognostic indicator for 32 (94%) of our 34 patients (39 [93%] of 42 affected ears).

Adult↗

Immunohistochemical detection of basic fibroblast growth factor as a prognostic indicator in pulmonary adenocarcinoma.

The expression of basic fibroblast growth factor (bFGF) was studied immunohistochemically in tissue specimens from 157 patients with pulmonary adenocarcinoma. Tumor cells that expressed bFGF were found in 89 patients (74%). The expression of bFGF was correlated with T and M in the TNM classification, disease stage and curability. The 5-year survival rate was 24% in bFGF-positive patients but 66% in bFGF-negative patients, the difference being significant (P<0.01). The 5-year survival rate of patients with stage I disease was 73% in those who were bFGF-positive but 88% in those who were bFGF-negative, the difference being significant (P<0.05). Multivariate analysis showed that the expression of bFGF was significantly related to prognosis. These findings suggest that bFGF plays an important role in tumor progression and that its expression may be a useful prognostic indicator for pulmonary adenocarcinoma.

Adenocarcinoma↗

Pulmonary shunt as a prognostic indicator in head injury.

Severe head injury may cause momentary respiratory arrest. Resultant hypoxia would increase cerebral edema and adversely affect the quality of survival. This study examines the effect of hypoxemia on outcome. Pulmonary shunt was calculated as a convenient measurement of respiratory insufficiency in 86 severely head-injured patients who underwent surgery. All samples were taken shortly after induction into anesthesia when controlled ventilation with high inspired-oxygen concentration had been established. In 39 patients who improved, mean pulmonary shunt was 8.9%. Twelve patients who survived with deficit showed a mean shunt of 13.6%, and in 35 patients who died, the mean initial shunt was 15.6%. No significant correlation was found between abnormal chest x-ray findings or the occurrence of hypertension and shunt percentage. The American Society of Anesthesiologists at-risk classification correlated grossly with the outcome. Early pulmonary shunt is a prognostic indicator in severe head injury and should be used in conjunction with the Glasgow Coma Scale in assessing outcome. Despite an apparently adequate respiratory pattern, all patients with severe head injury must be assumed to be hypoxic until proven otherwise. While hypoxemia may prove to be refractory in overwhelming injury, patients who score low on the Glasgow Coma Scale but who have relatively normal oxygen exchange may still survive with little deficit.

Adolescent↗

Prognostic indicators of breakthrough hepatitis during lamivudine monotherapy for chronic hepatitis B virus infection.

BACKGROUND: Breakthrough hepatitis (BTH), defined as a flare of transaminases alanine aminotransferase [ALT]) can occur during lamivudine monotherapy for hepatitis B virus (HBV) infection. There have been many reports of lamivudine-resistant mutations within the C domain of the viral reverse transcriptase; however, the appearance of these mutants is not necessarily correlated with BTH during lamivudine therapy. METHODS AND RESULTS: Entire serial HBV genomic sequences before and during lamivudine therapy for 4 patients with BTH and 1 patient without BTH were analyzed and showed changes in the pre-S region. These changes may be associated with ALT flares. Further investigation in a cohort of 36 patients with a median treatment period of 25 months showed that 21 patients had a rise in HBV-DNA titer, of whom 18 had BTH. Univariate statistical analyses showed that possible prognostic indicators for the occurrence of BTH were pre-S deletions ( P = 0.03) and L180M/M204L mutations ( P = 0.04). By multivariate Cox regression analyses, significant variables were pre-S deletions (hazard ratio, 0.17; 95% confidence internal (CI), 0.044-0.66) and precore mutations (hazard ratio, 5.70; 95% CI, 1.74-18.71) prior to the commencement of lamivudine monotherapy. Interestingly, BTH occurred after the selection of the wild-type species in the pre-S region during lamivudine monotherapy. CONCLUSIONS: These results suggest that patients with HBV pre-S deletion mutants should be monitored carefully during lamivudine therapy.

Adult↗

Serum alpha-fetoprotein. A prognostic indicator of liver-cell necrosis and regeneration following experimental injury by galactosamine in rats.

The serum concentrations of alpha-fetoprotein of rats following experimental galactosamine-induced liver-cell necrosis accurately reflect the severity of preceding liver-cell damage as determined by elevation of serum transaminases. There is a very close correlation between the highest SGOT or SGPT serum activity found 1-2 days after induction of necrosis and the subsequent elevation of alpha-fetoprotein at 2-6 days. Elevations of alpha-fetoprotein are associated in time with restitutive proliferation of the damaged liver. These experimental results clarify the temporal relationship between alpha-fetoprotein and repair of liver-cell damage, which has been suggested by similar observations in cases of patients who have acute or sub-acute viral hepatitis. The correlations support the concept that serum alpha-fetoprotein concentrations may be used as a prognostic indicator of the extent and course of fulminatn or subacute hepatitis.

Alanine Transaminase↗

Local infiltration of T-lymphocyte subsets as a prognostic indicator in patients with nasopharyngeal carcinoma.

We studied tumor-host interactions in 47 patients with NPC. The local infiltration of T-lymphocyte subsets was investigated by an immunoperoxidase technique using monoclonal antibodies. Biopsy specimens of patients without cervical metastasis showed more T-lymphocyte (T11) infiltration. The amount of Leu-3a (helper/inducer) and T8 (cytotoxic/suppressor) cell infiltration did not correlate with the age, sex, clinical stage, and peripheral blood T4 and T8 cells of the patients. A higher incidence of Leu-3a cell infiltration was found in patients with high serum IgA antibody titers to EBV VCA. A trend of better prognosis was revealed in those cases with no or slight stromal T8 cell infiltration. A local immune response was found to exist which may prevent the spread of NPC to the cervical nodes, but this needs further study to evaluate the local infiltration of T-lymphocyte subsets as a prognostic indicator.

Adult↗

N-methylnicotinamide as a possible prognostic indicator of recovery from leukaemia in patients treated with total-body irradiation and bone marrow transplants.

N-methylnicotinamide was determined in urine from patients with acute myelocytic leukaemia following total-body X-irradiation with 8.6 Gy and bone marrow transplantation. Patients that are alive and in excellent condition i.e. with acute leukaemia in full remission showed a distinct enhanced excretion of this metabolite about 20 days p.r. which returned to normal levels at about day 40 p.r. Patients that have died intercurrently of early leukaemic recurrences showed considerable fluctuations in N-methylnicotinamide excretion over the entire period and no "normalization" of levels in these patients was seen. In those cases where late leukaemic recurrence or infections were the cause of death, usually after discharge from the clinic, excretion patterns typical of those seen in disease-free patients were observed. We thus conclude that this metabolite appears to be a suitable tentative prognostic indicator for the overall state of recovery from leukaemia in the patients.

Adult↗

Radioimmunoassay for the detection of IgG antibodies to herpes simplex virus and its use as a prognostic indicator of HSV excretion in transplant recipients.

We report the development of a solid-phase radioimmunoassay for the detection of IgG antibodies to herpes simplex virus (HSV), using a mouse monoclonal antibody specific for the Fc portion of human IgG as the radiolabelled detecting antibody. The binding ratio to test antigen at a single serum dilution, 1:100, correlated significantly with the endpoint titre by radioimmunoassay and with neutralising antibody titre. When compared to neutralisation the radioimmunoassay had a sensitivity of 100% and a specificity of 93%. We believe that the anomalous results are not false positives but represent an increased sensitivity of the radioimmunoassay. We found, by either radioimmunoassay or neutralisation, that high levels of antibody prior to transplantation were associated with a significantly increased risk of HSV excretion post-transplantation in both renal and bone marrow transplant recipients. Thus the radioimmunoassay is a sensitive, specific, and rapid test that can be used as a prognostic indicator of HSV excretion in transplant recipients.

Antibodies, Viral↗

Individualized use of methadone and opioid rotation in the comprehensive management of cancer pain associated with poor prognostic indicators.

This case report describes a patient affected by a neuropathic pain syndrome, which was secondary to a renal cell carcinoma metastatic to the spine, and complicated by incidental components and somatization. Due to a rapid development of tolerance and toxicity from hydromorphone, a rotation to methadone was made, with a decrease of the morphine equivalent daily dose (MEDD) from 1050 to 36. After 4 mos of good pain relief, a switch over back to hydromorphone was necessary due to worsening pain, associated with myoclonus and sedation secondary to methadone; the MEDD this time escalated from 480 to 4950. The use of hydromorphone was complicated by the onset of intractable nausea and sedation. After 2 wks, the patient was rotated again to methadone, with a decrease of the MEDD to 24. He achieved good pain control and was free of opioid toxicity. Our findings illustrate a role of methadone in the management of cancer pain associated with poor prognostic indicators, the development of tolerance towards its effects, and the regaining of sensitivity to methadone, by temporary rotation to another opioid. Possible mechanism for opioid tolerance and its reversal are discussed.

Carcinoma, Renal Cell↗

A CD44 variant exon 6 epitope as a prognostic indicator in breast cancer.

The CD44 variant exon 6 sequence is associated with metastasizing clones of rat pancreatic and mammary carcinoma. In human breast and colorectal carcinoma epitopes on the cell surface encoded by exon v6 have been shown to predict poor chances of survival. Breast cancers in 55 patients whose clinical follow-up was available for 6 to 8 years were immunophenotyped for the presence of the CD44 exon v6 epitope and the results were correlated with survival. There was a difference in survival in the first 2.5 years following surgery: of the eight patients with negative tumours none had died during this period. The advantage of the negative group faded at later time points. However, the log-rank analysis revealed that differences between CD44 exon v6-negative and -positive groups were just below statistical significance. Studies with a larger number of patients are needed to establish the role of this CD44 variant as an early prognostic indicator in metastatic dissemination of breast cancer.

Antigens, Neoplasm↗

Prognostic indicators in idiopathic IgA mesangial nephropathy.

Univariate survivorship analysis of a cohort of 365 patients with idiopathic IgA mesangial nephropathy and at least one year of further observation since the apparent onset (mean = 7.79 +/- 6.19 years; median = 6.16 years) has been performed. Observations for at least one year (mean = 5.05 +/- 3.66; median = 4.08 years) after biopsy was available for 292 of these. One immunohistological, four clinical, and six histological features were associated with increased risk of developing renal failure: (i) older at onset; (ii) no history of recurrent macroscopic haematuria; (iii) proteinuria of more than 1 g/day; (iv) arterial hypertension at the time of biopsy; (v) extent of glomerular obsolescence; (vi) extent of segmental glomerulosclerosis; (vii) presence of interstitial fibrosis; (vii) presence of diffuse intracapillary proliferation; (ix) presence of extracapillary proliferation; (x) presence of segmental thickening of glomerular basement membrane; (xi) extension of IgA deposits to the peripheral capillary loops shown by immunofluorescence. Only features (iii), (v), (vii) and (xi) proved to be independent prognostic indicators in the multivariate survivorship analysis (Cox regression model).

Adolescent↗

FMRP expression as a potential prognostic indicator in fragile X syndrome.

Absence or deficit of FMR1 protein (FMRP) resulting from methylation of full mutation genes is the fundamental defect in fragile X syndrome. We used FMRP immunocytochemistry and detailed phenotypic assessment to investigate the relationship between degree of FMRP expression and the broad clinical spectrum of impairment in 80 individuals affected with fragile X syndrome. FMRP expression correlated with IQ in mosaic males (P=0.043), males with a partially methylated full mutation (P=0.0005), and females with a full mutation (P=0.046). In the females, FMRP expression also correlated with the number of fragile X physical features (P=0.0003). Even modest deficits in FMRP result in some manifestations of fragile X syndrome. In this initial study of 53 males, FMRP expression testing had a very high positive predictive value (100%, confidence interval of 29-100%) for a nonretarded IQ among males with expression of FMRP in > or = 50% of lymphocytes (3 males), suggesting that FMRP expression may have potential as a prognostic indicator in males with fragile X syndrome.

Adolescent↗

Expression of p53 protein as a prognostic indicator of reduced survival time in diffuse-type gastric carcinoma.

To determine whether p53 expression is different in intestinal and diffuse types of gastric carcinoma, we investigated p53 immunohistochemical expression in 178 primary gastric carcinomas. Overexpression of p53 was observed in 50 out of 100 intestinal-type tumors (50.0%) and in 27 out of 78 diffuse-type tumors (34.6%). A significant difference was found in the timing of p53 overexpression between the two types of carcinomas. Overexpression of p53 occurred often in the early stage of intestinal-type tumors, and there was no significant difference in expression between early and advanced cancers. In contrast, p53 overexpression did not occur often in the early stage of diffuse-type tumors, but it increased progressively as the tumor advanced. Analysis of patient survival revealed that p53 overexpression correlates significantly with a poor prognosis in diffuse-type gastric carcinoma (P = 0.003) but not in intestinal-type. Multivariate analysis showed that only pathological stage was an independent prognostic indicator. Our results suggest that p53 overexpression plays a different role in tumor carcinogenesis and progression of these two types of gastric cancers.

Adenocarcinoma↗

Epidermal growth factor and its receptor as prognostic indicators in Chinese patients with pancreatic cancer.

The expression of epidermal growth factor (EGF) and its receptor (EGFR) was studied immunohistochemically in fifty-seven Chinese patients with primary invasive ductal carcinoma (IDC) of the pancreas. The frequency of expression of EGF and EGFR was 73.7% and 68.4%, respectively. The frequency of their co-expression was 61.4%. No significant relationships were seen between the expression of EGF and its receptor and the patients' age, gender, site of the tumor, stage, and grade. Positive co-expression of EGF and EGFR was significantly associated with the poor prognosis. The median survival of the EGF(-)EGFR(-) group for 17.2 months was longer than that of the EGF(+)EGFR(+) group for 9.7 months (p = 0.02), as well as that of the other groups of EGR(+)EGFR(-), EGF(-)EGFR(+), and EGF(+)EGFR(+) for 9.9 month (p = 0.03). These results suggested that EGF and EGFR were frequently expressed in Chinese patients with IDC of the pancreas. Their co-expression may be a useful prognostic indicator for pancreatic cancer.

Adult↗

[Clinical effects of PSK on esophageal and gastric cancer patients and usefulness of serum levels of glycoproteins and HLA antigens as prognostic indicators].

This study was carried out to evaluate whether the preoperative levels of serum glycoproteins (CEA, SCC, TPA, IAP, ACT, ASP and sialic acid) and HLA antigens (class I and II) could be potential aids in the selection of suitable gastric and esophageal cancer patients for postoperative adjuvant immunotherapy of PSK. Gastric cancer patients underwent gastrectomy and received postoperative adjuvant chemotherapy (MMC, FT and ADR) with or without PSK. One hundred and forty esophageal cancer patients in cooperative study groups (organizing chairman; Dr. Hiroshi Satoh) underwent esophagectomy and received postoperative adjuvant radiotherapy and chemotherapy (FT, BLM) with or without PSK. The efficacy of PSK was recognized in the patients with normal levels of all glycoproteins in gastric cancer, and with normal levels of CEA or SCC or TPA and abnormal levels of one or more APRs in both gastric and esophageal cancer, and with positive HLA-B40 antigen. The combination of tumor-associated factors, such as CEA, SCC and TPA and various non-specific reactants such as APRs was useful as a prognostic indicator. In addition, some of HLA antigens were also valuable. The pretreatment levels of glycoproteins and HLA antigens have potential aids in the selection of patients with gastric and esophageal cancer for PSK treatment.

Adjuvants, Immunologic↗