The associations of CD4 count, CD4/CD8 ratio, and HIV viral load with survival from non-small cell lung cancer in persons living with HIV.

HIV status may influence survival from non-small cell lung cancer (NSCLC). Among NSCLC patients in the Bronx, NY, we assessed (1) associations of CD4 count, CD4/CD8 ratio and HIV viral load (VL) with survival and (2) prognostic factors among persons living with HIV (PLWH). We compared survival from NSCLC diagnosis (2004-2017) between HIV-negative persons (HIV-, n=2,881) and PLWH (n=88) accounting for clinical and sociodemographic factors. HIV-survival was also compared with PLWH, dichotomized by CD4 (<200 vs. ≥200cells/µL), CD4/CD8 (median, <0.43 vs. ≥0.43) and VL (<75 vs. ≥75copies/mL) at NSCLC diagnosis. Among PLWH, we assessed the relationships of CD4, CD4/CD8, and VL with survival, adjusting for age, sex, and cancer stage. PLWH with CD4< 200cells/µL had lower survival than HIV- [hazard ratio, 95% confidence interval [HR(95%CI)]=1.86(0.98-3.55)]. Survival was similar between PLWH with CD4≥ 200cells/µL and HIV- [HR(95%CI) = 0.90(0.61-1.33)]. Results were similar when categorizing PLWH by CD4/CD8 [vs. HIV-: low CD4/CD8: HR(95%CI) = 1.74(1.07-3.89); high CD4/CD8: HR(95%CI) = 0.63(0.37-1.07)] and VL [vs. HIV-: <75copies/mL: HR(95%CI) = 0.74(0.46-1.21), ≥75copies/mL: HR(95%CI) = 1.41(0.88-2.27)]. Among PLWH, CD4< 200cells/µL was associated with worse survival [vs. CD4≥ 200cells/µL: HR(95%CI) = 2.37(1.14-4.92)]. CD4, CD4/CD8, and VL may be prognostic markers for PLWH with NSCLC, suggesting immune status may be important in NSCLC survival among PLWH.

Prophylactic treatment to the fellow eye of patients with phakic lattice retinal detachment: analysis of failures and risks of treatment.

The authors performed a retrospective analysis on 296 phakic patients who had bilateral lattice degeneration and a retinal detachment in one eye. The analysis was done to determine the complications of full prophylactic treatment to lattice and breaks in the fellow eye and to explain the reasons that this treatment sometimes did not prevent new retinal breaks or detachments. The patients were followed for a mean +/- SD of 7.415 +/- 5.422 years after their first detachment. Twenty-four new tears occurred in the fellow eyes during this time, seven (29.2%) of which were away from areas of visible lattice. Prophylactic treatment did not appear to cause new tears or increase the risk of detachment if a new tear occurred. It also did not compromise the surgical repair in those patients who had eyes in which new breaks or detachments developed. The risk of visual loss was similar in those patients receiving prophylactic treatment compared with those not receiving treatment.

Differentiation of ischemic from non-ischemic central retinal vein occlusion during the early acute phase.

We investigated prospectively in 128 patients (140 eyes) the role of six routine clinical tests in the differentiation of ischemic central retinal vein occlusion (CRVO) from non-ischemic CRVO during its early acute phase. There were four functional tests [visual acuity, visual fields, relative afferent pupillary defect (RAPD), electroretinography (ERG)] and two morphologic tests (ophthalmoscopy and fluorescein fundus angiography). We found that none of the six tests had 100% sensitivity and specificity in such a differentiation during the early, acute phase, so that no one test can be considered a "gold standard"; however, combined information from all six is almost always reliable. Overall, the four functional tests proved far superior to the two morphologic tests in differentiating ischemic from non-ischemic CRVO:RAPD was most reliable in uniocular CRVO (with a normal fellow eye), followed closely by ERG in all cases; combined information from RAPD and ERG differentiated 97% of cases; perimetry was the next most reliable, followed by visual acuity. The two morphologic tests performed worst; fluorescein angiography provided either no information at all on retinal capillary nonperfusion (in at least one-third of the eyes during the early, acute phase) because of multiple limitations, or sometimes provided misleading information. Ophthalmoscopic appearance is the least reliable, most misleading parameter.

Factors prognostic of visual outcome in patients with subretinal hemorrhage.

We reviewed the charts of 29 patients with large subretinal hemorrhages involving the center of the fovea to evaluate factors that might be prognostic of visual outcome. The average final visual acuity was 20/480 with a mean follow-up of three years. Patients with thick hemorrhages (causing an obvious elevation of the fovea) had worse final visual acuity than patients with thin hemorrhages (P = .02). The diameter of the hemorrhage was not a significant predictor of outcome. Patients with aging macular degeneration had poorer final visual acuity (mean, 20/1,700, P = .002), and patients with choroidal ruptures had better final visual acuity, (mean 20/35, P less than .001) than the remainder of the patients. We found that the presence of aging macular degeneration was a more important predictor of the outcome of legal blindness than the thickness of the hemorrhage (P = .03). Although the prognosis in patients with subfoveal blood is generally poor, some patients have excellent return of vision.

Argon laser panretinal photocoagulation in ischemic central retinal vein occlusion. A 10-year prospective study.

We conducted a prospective, planned study of argon laser panretinal photocoagulation (PRP) in ischemic central retinal vein occlusion (CRVO) over a 10-year period in 123 eyes. On comparing the lasered eyes versus the nonlasered eyes, there was no statistically significant difference between the two groups in the incidence of development of angle neovascularization (NV), neovascular glaucoma (NVG), retinal and/or optic disc NV, or vitreous hemorrhage, or in visual acuity. Our study, however, did show a statistically significant (P = 0.04) difference in the incidence of iris NV between the two groups, with iris NV less prevalent in the laser group than in the nonlaser group, but only when the PRP was performed within 90 days after the onset of CRVO. The other parameter which showed a statistically significant difference between the two groups was the peripheral visual fields-the laser group suffered a significantly (P less than or equal to 0.03) greater loss than the non-laser group. We discuss the implications of these findings in light of the natural history of ischemic CRVO and of ocular NV. Since the original rationale for advocating PRP in ischemic CRVO was the proven beneficial effect of PRP on ocular NV in proliferative diabetic retinopathy, we also discuss the disparities in the disease process between ischemic CRVO and proliferative diabetic retinopathy and in their responses to PRP.

Low rejection rate when using unrelated or haploidentical donors for children with leukemia undergoing marrow transplantation.

Thirty-nine children with leukemia were entered into a bone marrow transplantation study comparing the use of unrelated donors who were HLA-Dr identical and matched at least with three of the four HLA-A or B loci, with haploidentical related donors. Although marrows were prepared by T lymphocyte depletion in vitro, the rejection rate of marrow in these patients was only 13% (5/39). Four patients had early rejections, and three of these four had autologous recovery immediately without evidence of leukemic recurrence. The fifth had a delayed rejection occurring approximately 2 1/2 months after transplant. These results were achievable by an ablative regimen incorporating increased immunosuppression. Although the small sample size does not yet permit evaluation of outcome comparing one donor type versus another, the early findings document a high rate of successful engraftment.

Electroretinography in central retinal vein occlusion. Correlation of electroretinographic changes with pupillary abnormalities.

In 149 eyes with central retinal vein occlusion (CRVO), we prospectively investigated the role of routine, clinical electroretinography (ERG) in differentiating ischemic (60 eyes) from nonischemic CRVO (89 eyes). Single-flash photopic and scotopic ERGs were recorded. Data for the amplitudes and implicit times of a- and b-waves and for the b-/a-wave amplitude ratio were analyzed in detail. The study revealed that the best ERG parameter (for both photopic and scotopic ERG) for differentiating ischemic from nonischemic CRVO was a subnormal b-wave amplitude (reduced to less than or equal to 60% or by greater than or equal to 1 SD from the normal mean value, or less than or equal to 64%-69% of that in the fellow normal eye), with a sensitivity of 80%-90% and a specificity of 70%-80%. ERG findings were correlated with the relative afferent pupillary defect (RAPD). An RAPD of greater than or equal to 0.7 log units showed a sensitivity of 88% and a specificity of 90% in differentiating ischemic from nonischemic CRVO. ERG and RAPD findings showed a good correlation. The combined ERG and RAPD tests could differentiate 97%-100% of ischemic from nonischemic CRVO cases, with a specificity of about 70%.

The fellow eye of patients with phakic lattice retinal detachment.

A retrospective study was performed to determine whether the prophylactic treatment of areas of lattice degeneration, holes, or breaks reduced the risk of subsequent new breaks or detachment in the fellow undetached phakic eyes of patients with a phakic lattice retinal detachment (RD). Three hundred eighty-eight consecutive patients who presented to the University of Iowa between 1959 and 1984 were followed for a mean of 7.9 +/- 5.8 years after the detachment in the first eye. Fellow eyes which received no prophylactic treatment had a 2.5 times greater risk of a new break or RD over 7 years than eyes receiving full prophylactic treatment (19.4 versus 7.5%; P = 0.0002). Fellow eyes receiving no treatment also had a greater risk of a new RD over 7 years than eyes receiving full treatment (5.1 versus 1.8%; P = 0.0125). These results do not allow us to make recommendations concerning which fellow eyes, if any, should be prophylactically treated. On the one hand, prophylactic treatment did significantly reduce the risk of new breaks and detachments. On the other hand, however, prophylactic treatment reduced the risk of new RD alone in the fellow eye only from 5.1 to 1.8% over 7 years. In addition, prophylactic treatment did not reduce the risk of detachment in the higher risk eyes with high myopia or extensive lattice.

Serum concentration and dose-response relationships for carprofen in rheumatoid arthritis.

Thirty-eight patients with active, definite, or classical rheumatoid arthritis were tested in a double-blind, 3-week-per-arm, multiple-crossover, randomized, block-design comparison of 100, 300, 600, and 800 mg/day carprofen given b.i.d. A linear dose-response relationship was demonstrated for six of nine efficacy measures (p less than 0.052). A plasma concentration to therapeutic response relationship was shown just before or 1 to 2 hours after a dose (p less than 0.05) for seven efficacy parameters for the patients with at least three serum carprofen concentrations. By nonparametric analysis, with the patients divided into three equal groups, the percent of responders rose from 38.1% to 50% to 59.1%. Sixty-nine percent of patients responded when carprofen concentrations were greater than 10 micrograms/ml, whereas only 9% responded when they were below 1.9 micrograms/ml. Although only seven patients had limiting side effects, there was a tendency toward a dose-toxicity relationship through 600 mg daily carprofen.

The therapeutic efficacy and cost-effectiveness of aggressive tocolysis for premature labor associated with premature rupture of the membranes.

We conducted a randomized trial comparing bed rest with tocolysis to determine the therapeutic efficacy, safety, and cost-effectiveness of tocolysis for the treatment of preterm labor after membrane rupture. One hundred nine women participated over a 26-month interval. Treatment groups did not differ significantly in terms of gestational age at membrane rupture, gestational age at delivery, birth weight, maternal or fetal infectious morbidity, respiratory distress syndrome, necrotizing enterocolitis, or perinatal mortality. Prolongation of intrauterine time after the onset of uterine contractions was seen in women receiving tocolysis (105.2 +/- 157 hours versus 62.1 +/- 77 hours, p = 0.06). This prolongation was not associated with a significant reduction in the total cost per surviving infant (tocolysis, $38,593 +/- $40,887 versus bed rest, $43,158 +/- $37,116; p = 0.445). The cost difference was artifactual. The number of very premature infants born (less than 28 weeks' gestation) was unequal in the two groups (12 in the bed rest group and 5 in the tocolysis group) and skewed the results. Before 28 weeks' gestation tocolysis was associated with a significant increase in intrauterine time after the onset of regular contractions (p = 0.05). However, there was no identifiable perinatal benefit garnered from the additional 5 days. After 28 weeks there were no significant differences between treatment groups in terms of intrauterine time after the onset of regular contractions and total cost per surviving infant. Because tocolysis does not improve perinatal outcome and can itself be associated with major maternal morbidity, it should be avoided after 28 weeks' gestation. Before 28 weeks' gestation tocolysis may greatly increase intrauterine time, but the benefit of this prolongation is not clear.

Pattern of response of megakaryocyte colony-stimulating activity in the serum of patients undergoing bone marrow transplantation.

Bone marrow transplantation has become an accepted form of therapy for several malignant, hematologic, and genetic disorders. Platelet recovery is delayed after bone marrow transplantation. To better understand the mechanisms involved in platelet recovery we studied 23 patients undergoing bone marrow transplantation for the presence of megakaryocyte colony-stimulating activity (Mk-CSA) in their serum. Shortly after beginning the pretransplant preparative regimen the Mk-CSA level in the serum of these patients increased. This increase was transient, and the level returned to baseline, to later increase again. The second increase in Mk-CSA level occurred during the second week after bone marrow transplantation at the time of hematopoietic recovery. Most patients who failed to engraft did not show a rise in Mk-CSA during the second week after transplantation. All patients showing engraftment had an Mk-CSA rise during the second week after transplantation. The difference between these two groups was highly significant (p = 0.0007). The biphasic response of Mk-CSA after bone marrow transplantation is similar to the response seen in a rat model after lethal irradiation. We postulate that the first elevation in Mk-CSA is due to tissue injury and nonspecific response whereas the second elevation of Mk-CSA is a physiologic response to marrow aplasia and associated with effective bone marrow engraftment.

Anterior ischemic optic neuropathy. VII. Incidence of bilaterality and various influencing factors.

A prospective study was conducted in 438 patients with anterior ischemic optic neuropathy (AION). There were 388 patients with nonarteritic AION and 50 with arteritic AION. The risk of bilaterality in patients with arteritic AION was found to be 1.9 times the risk in patients with nonarteritic AION (P = 0.0118). The cumulative incidence curve, considering the time taken to develop bilateral AION for nonarteritic cases was significantly (P = 0.0103) different from that for arteritic cases. The estimated 25th-percentile time to development of bilateral AION was much shorter in patients with arteritic AION (0.4 month) than in those with nonarteritic AION (32.4 months). In arteritic AION, unilateral as well as bilateral AION had almost invariably developed before systemic steroid therapy was started and not after, indicating that this therapy is effective in preventing the development of AION in giant cell arteritis. In nonarteritic AION, the risk of bilaterality was significantly greater in men (P = 0.0113) and in young (less than 45 years old) patients with diabetes (P = 0.0245), with no significant difference attributable to the other age groups or other associated systemic diseases. In this study, it was found that young diabetic men have a risk of AION developing in the second eye that is 1.56 times the risk in young diabetic women, 2.56 times the risk in women who either are nondiabetic or are not young, and 1.64 times the risk in both older men and nondiabetic men.

Diagnosis of gestational diabetes by capillary blood samples and a portable reflectance meter: derivation of threshold values and prospective validation.

Paired capillary-venous samples were obtained from 255 women undergoing a glucose challenge test and 116 women undergoing an oral glucose tolerance test. The capillary equivalents for the venous threshold values were calculated by regression analysis. The glucose challenge test predictions of either normal or abnormal agreed in 82%. The sensitivity, specificity, and positive and negative predictive values for the capillary oral glucose tolerance test were 89%, 90%, 62%, and 98%, respectively. These capillary equivalents were then applied prospectively to 147 women undergoing a glucose challenge test and 141 women undergoing an oral glucose tolerance test. The concurrence rate of the glucose challenge test in the prospective group was 90%. The sensitivity, specificity, and positive and negative predictive values for the capillary oral glucose tolerance test were 64%, 95%, 75%, and 92%. When the venous threshold recommendations of the American Diabetes Association were used instead of those standard at our institution, these values increased to 75%, 98%, 83%, and 96%, respectively. The recommended capillary values of the American Diabetes Association were 100% sensitive but had a positive predictive value of only 20%. Based on the prospective group, the cost per case of gestational diabetes identified would decline 63% if both a capillary glucose challenge test and an oral glucose tolerance test were used and 25% if the capillary glucose challenge test and venous oral glucose tolerance test were used. Combining the data set for new regression equations, the following venous-capillary threshold sets emerged: glucose challenge test, 140 mg/dl/150 mg/dl; fasting oral glucose tolerance test, 105 mg/dl/114 mg/dl; 1 hour, 190 mg/dl/211 mg/dl; 2 hours, 165 mg/dl/183 mg/dl; 3 hours, 145 mg/dl/157 mg/dl. The sensitivity, specificity, and negative predictive values for the capillary oral glucose tolerance test with these thresholds were 80%, 97%, 80%, and 97%. In conclusion, capillary glucose testing for diabetes during pregnancy is feasible and cost-effective.

Heparin-neutralizing activity in the plasma of women with gynecologic malignancy: the effect of tumor stage on heparin concentration and fibrin generation after low-dose heparin.

The relationship between tumor stage and the concentration of circulating heparin achieved after subcutaneous administration and its effect on fibrin generation were studied in 24 women with gynecologic malignancy. A single subcutaneous injection of 5000, 7500, and 10,000/U of sodium heparin was given in random order on different days. Plasma specimens for antithrombin III, fibrinopeptide A, and heparin were obtained serially over an 11-hour interval. Women with a Stage III or IV malignancy had significantly lower circulating heparin after the 5000 and 10,000/U doses. There was a significant decline in fibrinopeptide A as the concentration of circulating heparin increased. Thirty-three percent of women with a Stage III or IV malignancy had no detectable circulating heparin at any point examined over the 11 hours after 5000/U of heparin. Likewise, 16.7% and 8.4% had no detectable circulating heparin after 7500 and 10,000/U, respectively. A similar percentage was noted in a smaller group of women with Stage II malignancy. Next, a known quantity of heparin was added to the plasma from these patients and the concentration of heparin was determined. A significant amount of heparin-neutralizing activity was documented. We conclude that a large percentage of women with an advanced gynecologic malignancy are able to neutralize heparin administered for the prevention of thromboembolic disease. This heparin-neutralizing activity may account for the failure of low-dose heparin to prevent thromboembolic complications in this patient population.

Prediction of early beneficial response to plasma exchange in Guillain-Barré syndrome.

We attempted to identify predictive factors of early beneficial response to plasmapheresis in Guillain-Barré syndrome (GBS). We reviewed 24 patients with typical severe GBS who underwent plasmapheresis and analyzed their outcome at one month. One group of 14 patients, designated as responders, improved dramatically, while ten patients showed little response. Age was the only important clinical predictor, with responders being younger. No other clinical variable (sex, preceding illness, severity, timing of plasmapheresis, cranial nerve involvement, or cerebrospinal fluid findings) reached significance. Among electrophysiologic parameters obtained before plasmapheresis, the amplitudes of compound muscle action potentials with distal stimulation of median and peroneal nerves were significantly reduced in non-responders. Plasmapheresis may improve only a subgroup of patients with GBS. Among patient characteristics, age and amplitudes of compound muscle action potentials are important predictors of early responsiveness.

The relationship between capillary and venous glucose concentration during pregnancy.

Previous attempts to construct capillary equivalents of venous glucose values for prognostic purposes have failed. We examined the relationship between capillary and venous glucose concentration during pregnancy in 258 women who had samples taken at four different time intervals in relation to two different standardized meals. Capillary glucose concentration was determined with the Chemstrips bG and an Accu-Chek reflectance colorimeter and venous plasma glucose concentration was measured by the hexose kinase technique on an AutoAnalyzer. The capillary: venous relationship was constant over time for a given meal but the magnitude of the difference was affected by time. The capillary: venous relationship differed significantly between the two standard meals. The findings indicate that meal size and sampling time must be controlled for when one is attempting to construct capillary equivalents for venous derived norms. The failure of previous studies to control for these variables may explain their inability to construct useful capillary equivalents for venous glucose values. Our findings also indicate that attainment of venous norms with capillary specimens represent, in reality, tighter control.