[Propensity score comparison of the various radical surgical techniques for high-risk prostate cancer]. / Propensity Score Vergleich der verschiedenen radikalen Operationstechniken beim high risk Prostatakarzinom.

INTRODUCTION: The optimal surgical treatment of patients with a high risk prostate cancer (PCa) in terms of radical prostatectomy (RP) is still controversial: open retropubic RP (RRP), laparoscopic RP (LRP), or robot-assisted (RARP). We aimed to investigate the influence of the different surgical techniques on pathologic outcome and biochemical recurrence. PATIENTS AND METHODS: A total of 805 patients with a high risk PCa (PSA >20 ng/mL, Gleason Score ≥8, or clinical stage ≥cT2c) were included. A comparison of 407 RRP patients with 398 minimally invasive cases (LRP+RARP) revealed significant confounders. Therefore all 110 RARP cases were propensity score (PS) matched 1:1 with LRP and RRP patients. PS included age, clinical stage, preoperative PSA, biopsy Gleason score, surgeon's experience and application of a nerve sparing technique. Comparison of overall survival (OS) and recurrence-free survival (RFS) was done with the log rank test. Predictors of RFS were analyzed by means of Cox regression models. RESULTS: Within the post-matching cohort of 330 patients a pathologic Gleason score < 7, = 7 and > 7 was found in 1.8, 55.5 and 42.7% for RARP, in 8.2, 36.4, 55.5% for LRP and in 0, 60.9 and 39.1% for RRP (p=0.004 for RARP vs. LRP and p=0.398 for RARP vs. RRP). Differences in histopathologic stages were not statistically significant. The overall positive surgical margin rate (PSM) as well as PSM for ≥ pT3 were not different. PSM among patients with pT2 was found in 15.7, 14.0 and 20.0% for RARP, LRP and RRP (statistically not significant). The respective mean 3-year RFS rates were 41.4, 77.9, 54.1% (p<0.0001 for RARP vs. LRP and p=0.686 for RARP vs. RRP). The mean 3-year OS was calculated as 95.4, 98.1 and 100% respectively (statistically not significant). CONCLUSION: RARP for patients with a high risk PCa reveals similar pathologic and oncologic outcomes compared with LRP and RRP.

Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation.

OBJECTIVE: To compare time to achieve viral load <400 copies/ml and <1000 copies/ml in HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART). DESIGN: Retrospective cohort study. SETTING: Three university medical centers, USA. POPULATION: HIV-infected pregnant women initiated or restarted on HAART during pregnancy. METHODS: We calculated time to viral load <400 copies/ml and <1000 copies/ml in HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history. MAIN OUTCOME MEASURES: Time to HIV viral load <400 copies/ml and <1000 copies/ml. RESULTS: We evaluated 138 HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load < 400 copies/ml during pregnancy compared with 92% of ARV-experienced women (P = 0.82). The median number of days to achieve a viral load < 400 copies/ml in the ARV-naive cohort was 25.0 (range 3.5-133; interquartile range 16-34) days compared with 27.0 (range 8-162.5; interquartile range 18.5-54.3) days in the ARV-experienced cohort (P = 0.02). In a multiple predictor analysis, women with higher adherence (adjusted relative hazard [aRH] per 10% increase in adherence 1.29, 95% confidence interval [CI] 1.08-1.54, P = 0.01) and receiving a non-nucleotide reverse transcriptase inhibitor (NNRTI) -based regimen (aRH 2.48, 95% CI 1.33-4.63, P = 0.01) were more likely to achieve viral load <400 copies/ml earlier. Increased baseline HIV log10 viral load was associated with a later time of achieving viral load <400 copies/ml (aRH 0.60, 95% CI 0.39-0.92, P = 0.02). In a corresponding model of time to achieve viral load <1000 copies/ml, adherence (aRH per 10% increase in adherence 1.79, 95% CI 1.34-2.39, P < 0.001), receipt of NNRTI (aRH 2.95, 95% CI 1.23-7.06, P = 0.02), and CD4 cell count (aRH per 50 count increase in CD4 1.12, 95% CI 1.03-1.22, P = 0.01) were associated with an earlier time to achieve viral load below this threshold. Increasing baseline HIV log10 viral load was associated with a longer time of achieving viral load <1000 copies/ml (aRH 0.54, 95% CI 0.34-0.86, P = 0.01). In multiple predictor models, previous ARV exposure was not significantly associated with time to achieve viral load below thresholds of <400 copies/ml and <1000 copies/ml. CONCLUSIONS: Pregnant women with ≥50% adherence, whether ARV-naive or ARV-experienced, on average achieve a viral load <400 copies/ml within a median of 26 days and a viral load of <1000 copies/ml within a median of 14 days of HAART initiation. Increased adherence, receipt of NNRTI-based regimen and lower baseline HIV log10 viral load were all statistically significant predictors of earlier time to achieve viral load <400 copies/ml and <1000 copies/ml. Increased CD4 count was statistically significant as a predictor of earlier time to achieve viral load <1000 copies/ml.

Adverse effects of dietary and furosemide-induced sodium depletion on thermoregulation.

In this study, the diuretic furosemide was used in combination with dietary sodium (Na) restriction to quantify the effects of moderate to severe Na depletion on heat tolerance in a validated model of heat stress in rats. Rats were subjected to an Na depletion regimen as follows: a control group (I, n = 17) had free access to a normal diet and tap water; group II (n = 20) consumed the same normal diet and tap water, but was treated with the diuretic furosemide at a dose of 10 mg.kg-1.d-1, ip; group III (n = 18) had free access to an Na-free diet and deionized drinking water; group IV (n = 21) consumed the same Na-free diet and electrolyte-free water, but was also treated with furosemide. Both the dietary and drug manipulations affected significant (p less than 0.05) negative electrolyte and water balances. Group IV consistently exhibited the greatest decrements. Following the 4-d depletion all four groups were acutely exposed to a 42 degrees C, 25-30% rh environmental heat stress during which time core body temperature increased. The time required for rectal temperature to reach 42.6 degrees C was significantly (p less than 0.05) decreased from a time of 242 +/- 8 min in the control group to 176 +/- 14, 181 +/- 8, and 111 +/- 11 min in groups II, III and IV, respectively. We concluded that Na deprivation and diuretic treatment can elicit a 25-50% reduction in heat tolerance due to electrolyte depletion and dehydration. These data confirm that during environmental heat stress uncompensated negative Na balance may predispose an individual to heat illnesses.

Plasma renin activity and aldosterone: correlations with moderate hypohydration.

Adult male test subjects (n = 16) were assigned to one of three clothing configurations (Army fatigues, fatigues with impermeable chemical protective garments, and fatigues with protective garments plus protective masks) prior to exercise (level treadmill, 1.11 m/s, 50 min/h, 6 h) in a moderate (wet bulb globe temperature, WBGT = 23 degrees C) environment with ad lib water consumption. When protective masks were worn, two through-mask drinking systems were evaluated: the current gravity-fed system for fluid delivery and a new system utilizing a small hydraulic pump (Fist-Flex). Antecubital blood samples were taken prior to the start of and subsequent to the completion of exercise and analyzed for fluid-electrolyte regulatory hormones. During all trials with chemical protective garments, plasma renin activity (PRA) and aldosterone levels (PA) were significantly (p less than 0.05) elevated following the exercise protocol while neither was affected during exercise in fatigues only. Individual hypohydration levels during all trials ranged from low (0.84%) to moderate (4.04%). Levels of PRA were closely correlated (r = 0.635, t = 4.35, p less than 0.001) with hypohydration as measured by percentage of body weight lost during the 6 h trial. Likewise, PA was also correlated (r = 0.47, t = 2.81, p less than 0.01) with body weight loss. We concluded from this study that PRA and PA responses were exacerbated in moderate environments by the additional heat stress, sweat rate, and dehydration caused by the impermeable garments. Further, the logistical difficulty inherent in delivering fluid through the chemical protective mask reduced voluntary consumption, increased hypohydration, and elicited the greatest elevations in PRA and PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma cortisol, renin, and aldosterone during an intense heat acclimation program.

The physiologic responses to an intense heat acclimation (HA) regimen (treadmill, 41.2 degrees C, 8 days, 56 min exercise/44 min rest) and the effects on stress and fluid balance hormone responses were examined in 13 unacclimated male volunteers. Venous blood samples were collected before (PRE) and after (POST) exercise (days 1, 4, 8) and analyzed for plasma renin activity (PRA), aldosterone (ALD), cortisol (PC), plasma volume shifts (delta PV%), sodium concentration (Na+), and potassium concentration (K+). HA responses (day 1 vs day 8) indicated reduced strain (P less than 0.05): decreased heart rate, rectal temperature, skin temperature, improved defense of PV, and attenuated PC responses. While plasma Na+ demonstrated no change during daily exercise, K+ (P less than 0.01), PC, PRA, and ALD increased (P less than 0.05) more than delta PV%(day 1: -7.1%, day 8: -5.1%) accounted for. Na+ and K+ did not change as a result of HA, and there was no change in fluid balance hormones (e.g., PRA, ALD). It was concluded that this intense heat acclimation regimen reduced physiologic strain by mechanisms other than alterations in fluid balance hormones and offered few physiologic advantages which cannot be gained through conventional heat acclimation techniques (e.g., walking).

Responses of plasma human atrial natriuretic factor to high intensity submaximal exercise in the heat.

No data exists regarding responses of human atrial natriuretic factor (ANF) to exercise in the heat. The purpose of this study was to examine the responses of plasma ANF to high intensity submaximal (71% +/- 0.9 VO2max) exercise in the heat over an eight day acclimation period. Fourteen healthy males volunteered to participate in the study. Subjects performed intermittent exercises on a treadmill (0% grade) during 50 min of each 100 min trial in an environmental chamber maintained at 41.2 +/- 0.5 degrees C, 39.0 +/- 1.7% relative humidity. Blood was obtained from an antecubital vein after standing 20 min in the heat prior to exercise, and immediately after exercise. Measures were compared on days 1, 4 and 8. ANF did not change pre- to post-exercise nor did it change over the eight day heat acclimation period despite other heat acclimation adaptations. Conversely, plasma aldosterone (ALDO), renin activity (PRA) and cortisol (COR) all increased (p less than 0.05) pre- to post-exercise on each day but again no changes were observed over the eight day period. These data support that ANF may not increase when ALDO and PRA increases are observed.

Plasma opioid peptide responses during heat acclimation in humans.

Plasma beta-endorphin, Met-enkephalin and Peptide F immunoreactivity (ir) were measured at rest and following exercise on three days (days 1, 4, 8) of an eight day heat acclimation regime. Fourteen male subjects demonstrated physiological heat acclimation adaptations. Our data demonstrated a differential response of peripheral plasma levels of endogenous opioid peptides (EOP) to exercise in the heat. In addition, EOP did not follow the same time-course of other physiological adaptations as no differences (day 1 vs. 4 vs. 8) in resting or exercise levels were observed over the eight day heat acclimation regime. Significant increases in beta-endorphin ir (pre- to post-exercise) appear to reflect concomitant exercise-heat related changes. The increased peripheral levels of beta-endorphin were correlated to plasma levels of cortisol. Heat and exercise stress may result in a reduction of Met-enkephalin ir observed in peripheral plasma and might be due to degradation or a decrease in processing from the larger precursors. The differential responses of EOP suggest the possibility of separate physiological roles for these peptides during exercise in the heat but peripheral plasma levels of EOP do not appear to reflect acute heat acclimation changes.

Urinary and hematologic indexes of hypohydration.

As part of a large-scale field feeding system test we were able to collect and study hundreds of aliquots of overnight urine samples obtained immediately prior to a fasting blood sample on days 1, 20, and 44 of the field test. The large number of experimental samples (greater than 650) and concomitant collection of blood and urine aliquots along with data on body weights gave us the opportunity to assess and quantitate the sensitivity of commonly used criteria of hypohydration. Urine aliquots for all test days were initially categorized by specific gravity (SG) greater than or equal to 1.03 (n = 124) or less than 1.03 (n = 540). Creatinine levels were elevated (P less than 0.001) in the concentrated urine samples, but a decreased trend in sodium-to-potassium ratios in these samples failed to achieve statistical significance (P greater than 0.05). However, when individuals with high SG urine were subclassified by a criterion of weight loss greater than 3% from original body weight, then creatinine concentrations were elevated (P = 0.05), whereas sodium-to-potassium ratios were decreased (P = 0.05) when subjects also with high SG but weight loss less than 3% were compared. Because of the moderate altitude (2,000 m) of the field site and the time of sojourn (44 days), there occurred a slight, but significant (P less than 0.001), erythropoietic response. Hematocrit and serum osmolality were not significantly different when examined by the criteria of high or low SG urine and weight loss greater than or less than 3% original body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral pyridostigmine administration in rats: effects on thermoregulation, clinical chemistry, and performance in the heat.

We have recently reported that acute intraperitoneal administration of pyridostigmine bromide to rats resulted in significant decrements in physical performance in the heat, adverse thermoregulatory effects, and exacerbated elevations in several indices of heat/exercise injury. Since it will be consumed orally as a prophylaxis for organophosphate poisoning, pyridostigmine was dissolved in the drinking water of rats. Consumption of pyridostigmine for 7 days (n = 34, 6.6 mg/day) resulted in a 23% (p less than 0.001) reduction of circulating cholinesterase when compared with a control group (n = 31) while ingestion for 14 days (n = 35, 8.9 mg/day) elicited a 39% (p less than 0.001) inhibition of circulating cholinesterase when compared to a second control group (n = 33). Water and food consumption, rate of weight gain, and overt behavior were unaffected by pyridostigmine consumption. When approximately half the animals in each group were exercised (9.14 m/min) in the heat (35 degrees C) to hyperthermic exhaustion (Tre = 42.5-43 degrees C, rats unable to right themselves), pyridostigmine consumption for 14 days effected a significantly (p less than 0.05) increased rate of weight loss, but no further effects on thermoregulation or performance were noted. Several minor increments were observed in clinical indices of heat/exercise injury in rats consuming pyridostigmine for 14 days. These data indicate that oral dosages of pyridostigmine can probably be titrated to levels of cholinesterase inhibition which are efficacious in prophylaxis against organophosphate toxicity without significant effects on selected physiologic and metabolic processes.