Changes in body composition in early breast cancer patients treated with aromatase inhibitors.

PURPOSE: The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs). METHODS: This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors. RESULTS: A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively. CONCLUSION: Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.

The relationship between feed efficiency and the circadian profile of blood plasma analytes measured in beef heifers at different physiological stages.

The characterization of blood metabolite concentrations over the circadian period and across physiological stages is important for understanding the biological basis of feed efficiency, and may culminate in indirect methods for assessing feed efficiency. Hematological analyses for albumin, urea, creatine kinase, glutamate dehydrogenase, aspartate aminotransferase, carbon dioxide, and acetate were carried out in growing and gestating heifers. These measures were carried out in a sample of 36 Bos taurus crossed beef heifers held under the same husbandry conditions. Hourly blood samples were collected over a 24-h period on three separate sampling occasions, corresponding approximately to the yearling (and open), early-gestation and late-gestation stages. This design was used to determine variation throughout the day, effects due to physiological status and any associations with feed efficiency, as measured by residual feed intake. Blood analyte levels varied with time of day, with the most variation occurring between 0800 and 1600 h. There were also considerable differences in analyte levels across the three physiological stages; for example, creatine kinase was higher (P<0.05) in open heifers, followed by early- and late-gestation heifers. Feed efficiency was also associated with analyte abundance. In more feed-efficient open heifers, there were higher activities of creatine kinase (P<0.05) and aspartate aminotransferase (P<0.05), and lower concentrations of carbon dioxide (P<0.05). Furthermore, in late gestation, more efficient heifers had lower urea concentrations (P<0.05) and lower creatine kinase levels (P<0.05). Over the whole experimental period, carbon dioxide concentrations were numerically lower in more feed efficient heifers (P=0.079). Differences were also observed across physiological stages. For instance, open heifers had increased levels (P<0.05) of creatine kinase, aspartate aminotransferase, carbon dioxide than early and late pregnancy heifers. In essence, this study revealed relevant information about the metabolic profile in the context of feed efficiency and physiological stages. Further optimization of our approach, along with the evaluation of complementary analytes, will aid in the development of robust, indirect assessments of feed efficiency.

Intra-operative ultrasound facilitates the localization of the calcific deposit during arthroscopic treatment of calcifying tendinitis.

PURPOSE: Calcifying tendinitis is a common condition of the shoulder. In many cases, arthroscopic reduction in the deposit is indicated. The localization of the deposit is sometimes challenging and time-consuming. Pre-operative ultrasound (US)-guided needle placement in the deposit and pre-operative US marking of the deposit at the skin with a ballpoint are described and recommended methods to alleviate the procedure without using ionizing radiation by fluoroscopy. METHODS: Intra-operative sonography of the shoulder is introduced as a new method to localize the calcific deposit with high accuracy. After standard arthroscopic buresectomy, the surgeon performs an ultrasound examination under sterile conditions to localize the deposits. A ventral longitudinal US section is recommended, and the upper arm is rotated until the deposit is visible. Subsequently, perpendicular to the skin at the position of the transducer, a needle is introduced under arthroscopic and ultrasound visualization to puncture the deposit. RESULTS: The presence of snow-white crystals at the tip of the needle proves the exact localization. Consecutively, the curettage can be accomplished. Another intra-operative sonography evaluates possible calcific remnants and the tendon structure. CONCLUSION: This new technique may alleviate arthroscopic calcific deposit curettage by visualizing the deposit without using ionizing radiation. Additionally, soft tissue damage due to decreased number of punctures to detect the deposit may be achieved. Both factors may contribute to reduced operation time.

Effect of earplugs on propofol requirement and awareness with recall during spinal anesthesia.

UNLABELLED: investigator either placed or did not place earplugs into the patients' ears (PLUG or noPLUG groups, respectively). Propofol requirements for stable sedation guided by the bispectral index and incidence of postoperative recall of intraoperative events were assessed in a double-blinded fashion. RESULTS: We found high but comparable propofol requirements in both groups (PLUG 4.4+/-1.2 vs. noPLUG 4.2+/-1.0 mg kg-1 h-1, p=NS). The incidence of intraoperative awareness was lower in the PLUG compared to the noPLUG group (16 vs. 56%; P<0.001). CONCLUSION: Although no sedative-sparing effect could be found in patients who wore earplugs during elective orthopedic surgery under spinal anesthesia, we nevertheless recommend using single-use paraffin wax earplugs. Beside their beneficial effect against potential harmful intraoperative noise, they reduce the incidence of intraoperative awareness with recall.

Comparison of economical aspects of interscalene brachial plexus blockade and general anaesthesia for arthroscopic shoulder surgery.

BACKGROUND: This study investigated the cost-effectiveness of ultrasonographic-guided interscalene brachial plexus blockade (ISB) in comparison with general anaesthesia (GA) for arthroscopic shoulder surgery. METHODS: Forty patients undergoing arthroscopic shoulder surgery received either an ultrasonographic-guided ISB or GA. ISB was performed outside the operation room (OR) and patients were transferred in the OR at the earliest 20 min after block performance. All drugs and disposables were recorded to evaluate the costs for both techniques. The following anaesthesia-related times were defined: ready for surgical preparation (from arrival in the OR until end of anaesthesia induction), OR emergence time (from end of dressing until leaving the OR), anaesthesia control time (from patient's arrival in the OR until readiness for positioning plus time from the end of surgery to patient's discharge from the OR), and post-anaesthesia care unit (PACU) time (from patient's arrival in the PACU to the eligibility for discharge to normal ward). Personnel costs were excluded from statistical analysis. RESULTS: The total costs were [mean (sd)] 33 (9)euro for patients with ISB and 41 (7)euro for those who received GA (P<0.01). The anaesthesia-related workflow was improved in the ISB group when compared with the GA group [ready for surgical preparation 8 (3) vs 13 (5) min, P<0.001; OR emergence time 4 (3) vs 10 (5), P<0.001; anaesthesia control time 12 (4) vs 23 (6), P<0.001; and PACU time 45 (17) vs 70 (20), P<0.001]. CONCLUSIONS: Ultrasonographic-guided ISB is a cost-effective method for arthroscopic shoulder surgery.

Remifentanil for tracheal tube tolerance: a case control study.

We assessed the minimal remifentanil dosage required for tracheal tube tolerance in awake and spontaneously breathing patients after major abdominal surgery. Forty postoperative patients received remifentanil 0.1 microg.kg(-1).min(-1), which was reduced in steps of 0.025 microg.kg(-1).min(-1) every 30 min. Respiratory response subscore of comfort scale (CSRR), Ramsay sedation scale (RSS), visual analogue scale (VAS), respiratory rate, and minute ventilation were recorded. Spontaneous respiration with no or little response to ventilation (CSRR 2) in co-operative, oriented and tranquil patients (RSS 2) was defined as the main outcome and study endpoint. Thirty-one patients (77.5%) reached a CSRR 2 and RSS 2 with remifentanil 0.025 microg.kg(-1).min(-1) and nine patients (22.5%) required remifentanil 0.05 microg.kg(-1).min(-1). Analgesia was sufficient in all patients (VAS = 30). Remifentanil 0.025-0.05 microg.kg(-1).min(-1) achieves satisfactory tracheal tube tolerance in awake and spontaneously breathing patients.

Effect of newer anaesthetics on duration of stay in postanaesthesia care unit in patients undergoing major abdominal surgery.

Newer anaesthetic agents, such as remifentanil and sevoflurane, are more expensive than conventional anaesthetics, such as isoflurane and fentanyl. However, newer anaesthetics might outweigh their higher acquisition costs by reducing length of stay in the postanaesthesia care unit and thereby reducing personnel costs. We retrospectively investigated the influence of newer anaesthetics on time to eligibility for discharge from the postanaesthesia care unit in consecutive patients undergoing major abdominal surgery. Using a chart review, patients undergoing major abdominal surgery with three different anaesthetic regimens (isoflurane/fentanyl (n = 80), sevofluranelfentanyl (n = 40), and sevoflurane/remifentanil (n = 42)) were compared regarding duration of anaesthesia, surgery, time till extubation, and time to eligibility for discharge from the postanaesthesia care unit. Extubation times were shorter in patients in the sevoflurane/fentanyl and the sevoflurane/remifentanil groups compared to patients in the isoflurane/fentanyl group. Time to eligibility to discharge from the postanaesthesia care unit was similar in isoflurane/fentanyl and sevoflurane/fentanyl group. In the sevoflurane/fentanyl group, time to eligibility for discharge from the unit showed a tendency to be increased (P = 0.08), however these patients were significantly older compared to the other groups. Sevoflurane and remifentanil did not appear to reduce time to eligibility to discharge from the postanaesthesia care unit in our patients undergoing major abdominal surgery compared to isoflurane and fentanyl. This study highlighted the necessity for carefully planned transition from remifentanil to other longer-acting analgesia in our patients.

Anticoagulation with prostaglandin E1 and unfractionated heparin during continuous venovenous hemofiltration.

OBJECTIVE: To determine the effect of two doses of prostaglandin E1 (PGE1, alprostadil) combined with unfractionated heparin on the hemofilter life-span and the coagulation profile during continuous venovenous hemofiltration. DESIGN: Prospective, randomized, controlled trial. SETTING: Intensive care unit at a university-affiliated hospital. PATIENTS: Twenty-four critically ill, mechanically ventilated patients with postoperative acute renal failure who require continuous venovenous hemofiltration. INTERVENTIONS: The patients were anticoagulated with 5 ng/kg/min PGE1 and 6 IU/kg/hr heparin or 20 ng/kg/min PGE1 and 6 IU/kg/hr heparin, injected into the extracorporeal circuit before the hemofilter. MEASUREMENTS AND MAIN RESULTS: The life-span of 43 hemofilters was evaluated. They were used until extracorporeal line pressure exceeded 250 mm Hg, ultrafiltration rate decreased to 16 mL/min, or grossly visible extracorporeal clotting occurred. Blood was sampled from the afferent (prefilter) and efferent (postfilter) lines of the extracorporeal circuit. Platelet counts, in vitro platelet function, plasma concentrations of platelet factor 4, prothrombin fragment F1+2, thrombin-antithrombin complex, routine plasma coagulation tests, and hemodynamic profile were determined before and during hemofiltration. Hemofilter usage was significantly longer in patients anticoagulated with 20 ng/kg/min PGE1 (32 +/- 3 [SEM] hrs) than with 5 ng/kg/min PGE1 (22 +/- 3 hrs). In vitro bleeding parameters were significantly prolonged in postfilter blood in patients receiving 20 ng/kg/min PGE1. Prefilter, there was no antiplatelet activity in either group and platelet counts remained stable. No intra- or intergroup differences in plasma coagulation profile or hemodynamic parameters were detected. CONCLUSION: Extracorporeal administration of PGE1, combined with low-dose heparinization, inhibits platelet reactivity and preserves hemofilter life dose-dependently.

Effects of hypothermia on thrombelastography in patients undergoing cardiopulmonary bypass.

Thrombelastography (TEG) correlates with postoperative chest drain output in patients undergoing cardiopulmonary bypass (CPB). In vitro incubation with heparinase allows TEG monitoring during CPB, despite heparin anticoagulation. Hypothermia impairs coagulation, but these effects cannot be assessed by standard coagulation tests performed at 37 degrees C. The aim of this study was to assess the effects of hypothermia on TEG. Therefore, we have compared normothermic and temperature-adapted TEG in 30 patients undergoing CPB. Our data showed significantly impaired reaction time (r), kinetic time (k), and angle alpha (alpha) in temperature-adapted compared with normothermic TEG. Maximum amplitude (MA), reflecting absolute clot strength, was not affected at temperatures of 33-37 degrees C. These findings indicate a decrease in the speed of clot formation, but not absolute deterioration in clot quality. Furthermore, heparinase-modified TEG indicated that there were nine cases in which heparin effects persisted after heparin reversal with protamine, providing a rational guide to protamine therapy.

Endogenous heparin-like substances significantly impair coagulation in patients undergoing orthotopic liver transplantation.

UNLABELLED: Orthotopic liver transplantation (OLT) is associated with severe bleeding, especially after reperfusion of the grafted liver. Heparin released from the liver graft contributes to postreperfusion coagulopathy. Although patients with liver cirrhosis have increased levels of endogenous heparinoids, the role of these substances during liver transplantation is unclear. Therefore, we performed native and heparinase-modified thrombelastography (TEG) in 72 patients undergoing OLT. TEG was performed at skin incision, 10 min before and 10 min after clamping of the vena cava, 10 min before and 10 min after graft perfusion, and at the end of surgery. Heparinase-modified TEG compared with native TEG demonstrated heparin activity. In contrast to other investigations, we found significant heparin effects before reperfusion, although patients received no exogenous heparin. These heparin effects were greater in patients with cirrhosis compared with patients with cancer as the underlying disease leading to OLT. Administration of coagulation factors is the usual treatment of coagulopathies during OLT. The comparison of native versus heparinase-modified TEG can distinguish between heparin activity or coagulation factor deficiency as a cause of bleeding complications and provides a rational approach to the treatment of bleeding during OLT. IMPLICATIONS: Impaired coagulation function, contributed to by heparin or heparin-like substances, is frequently observed after reperfusion of a transplanted liver. This study demonstrates that a heparinase-modified thrombelastography can identify significant heparin effects in the absence of exogenous heparin administration in patients undergoing liver transplantation.

Distribution of diaphragmatic lymphatic lacunae.

The morphology of the submesothelial lymphatic lacunae on the pleural and peritoneal surface over the tendinous and muscular portion of the diaphragm was studied in 10 anesthetized rabbits. The lymphatic network was evidenced by injecting 1 ml of colloidal carbon solution in the pleural (n = 5) or the peritoneal (n = 5) space. After 1 h of spontaneous breathing, the animal was killed and the diaphragm was fixed in situ by injection of approximately 5 ml of fixative in pleural and peritoneal spaces. Then both cavities were opened and the diaphragm was excised and pinned to a support. According to which cavity had received the injection, the peritoneal or the pleural side of the diaphragm was scanned by sequential imaging of the whole surface by use of a video camera connected to a stereomicroscope and to a video monitor. The anatomic design appeared as a network of lacunae running either parallel or perpendicular to the major axis of the tendinous or muscular fibers. The lacunae were more densely distributed on the tendinous peritoneal area than on the pleural one. Scanty lacunae were seen on the muscular regions of both diaphragmatic sides, characterized by large areas without lacunae. The average density of lacunae on tendinous and muscular regions was 6 and 1.7/cm2 for the pleural side and 25 and 3.4/cm2 for the peritoneal side, respectively. The average width of lacunae was 137.9 +/- 1.6 and 108.8 +/- 1.7 microns on the tendinous pleural and the peritoneal side, respectively, and 163 +/- 1.8 microns on the muscular portion of the pleural and peritoneal surfaces.

Microvascular pressure profile in intact in situ lung.

We measured the microvascular pressure profile in lungs physiologically expanded in the pleural space at functional residual capacity. In 29 anesthetized rabbits a caudal intercostal space was cleared of its external and internal muscles. A small area of endothoracic fascia was surgically thinned, exposing the parietal pleura through which pulmonary vessels were clearly detectable under stereomicroscopic view. Pulmonary microvascular pressure was measured with glass micropipettes connected to a servo-null system. During the pressure measurements the animal was kept apneic and 50% humidified oxygen was delivered in the trachea. Pulmonary arterial and left atrial pressures were 22.3 +/- 1.5 and 1.6 +/- 1.5 (SD) cmH2O, respectively. The segmental pulmonary vascular pressure drop expressed as a percentage of the pulmonary arterial to left atrial pressure was approximately 33% from pulmonary artery to approximately 130-microns-diam arterioles, 4.5% from approximately 130- to approximately 60-microns-diam arterioles, approximately 46% from approximately 60-microns-diam arterioles to approximately 30-microns-diam venules, approximately 9.5% from 30- to 150-microns-diam venules, and approximately 7% for the remaining venous segment. Pulmonary capillary pressure was estimated at approximately 9 cmH2O.

Parenchymal stress affects interstitial and pleural pressures in in situ lung.

After resecting the intercostal muscles and thinning the endothoracic fascia, we micropunctured the lung tissue through the intact pleural space at functional residual capacity (FRC) and at volumes above FRC to evaluate the effect of increasing parenchymal stresses on pulmonary interstitial pressure (Pip). Pip was measured at a depth of approximately 230 microns from the pleural surface, at 50% lung height, in 12 anesthetized paralyzed rabbits oxygenated via a tracheal tube with 50% humidified O2. Pip was -10 +/- 1.5 cmH2O at FRC. At alveolar pressure of 5 and 10 cmH2O, lung volume increased by 8.5 and 19 ml and Pip decreased to -12.4 +/- 1.6 and -12.3 +/- 5 cmH2O, respectively. For the same lung volumes held by decreasing pleural surface pressure to about -5 and -8.5 cmH2O, Pip decreased to -17.4 +/- 1.6 and -23.8 +/- 5 cmH2O, respectively. Because Pip is more negative than pleural pressure, the data suggest that in intact pulmonary interstitium the pressure of the liquid phase is primarily set by the mechanisms controlling interstitial fluid turnover.

Distribution of diaphragmatic lymphatic stomata.

In seven anesthetized rabbits we measured the size, shape, and density of lymphatic stomata on the peritoneal and pleural sides of the diaphragm. The diaphragm was fixed in situ and processed for scanning electron microscopy. Results are from 2,902 peritoneal and 3,086 pleural fields (each 1,620 microns 2) randomly chosen from the various specimens. Stomata were seen in 9% of the fields examined, and in 30% of the cases they appeared grouped in clusters with 2-14 stomata/field. Stoma density was 250 +/- 242 and 72 +/- 57 (SD) stomata/mm2 on peritoneal and pleural sides, respectively, and it was similar over the muscular and tendinous portion of the two surfaces. The maximum diameter ranged from less than 1 to approximately 30 microns, with an average value of 1.2 +/- 3.1 micron. The ratio of the maximum to the minimum diameter and the surface area averaged 2 +/- 1.4 and 0.7 +/- 2.4 micron 2, respectively. The maximum and minimum diameter and surface area values followed a lognormal frequency distribution, suggesting that stomata geometry is affected by diaphragmatic tension.

Direct measurement of interstitial pulmonary pressure in in situ lung with intact pleural space.

We developed an experimental approach to measure the pulmonary interstitial pressure with the micropuncture technique in in situ lungs with an intact pleural space. Experiments were done in anesthetized paralyzed rabbits that were oxygenated via an endotracheal tube with 50% humidified oxygen and kept in either the supine or the lateral position. A small area of an intercostal space was cleared of the intercostal muscles down to the endothoracic fascia. Subsequently a "pleural window" was opened by stripping the endothoracic fascia over a 0.2-cm2 surface and leaving the parietal pleura (approximately 10 microns thick). Direct micropuncture through the pleural window was performed with 2- to 3-microns-tip pipettes connected to a servo-null pressure-measuring system. We recorded pleural liquid pressure and, after inserting the pipette tip into the lung, we recorded interstitial pressure from subpleural lung tissue. Depth of recording for interstitial pressure averaged 263 +/- 122 (SD) microns. We report data gathered at 26, 53, and 84% lung height (relative to the most dependent portion of the lung). For the three heights, interstitial pressure was -9.8 +/- 3, -10.1 +/- 1.6, and -12.5 +/- 3.7 cmH2O, respectively, whereas the corresponding pleural liquid pressure was -3.4 +/- 0.5, -4.4 +/- 1, and -5.2 +/- 0.3 cmH2O, respectively.

Transperitoneal fluid dynamics in rabbit liver.

The peritoneal cavity of 18 anesthetized spontaneously breathing supine rabbits was opened through a midline section. One or two hollow capsules (surface area 0.8 cm2) were glued to the exposed liver surface, filled with whole or 25% diluted plasma, and connected to a transducer and a graduated pipette. Various hydraulic pressures (Pcap) were set in the capsule; at each Pcap the liquid flow per unit surface area (V/S) between the Disse's interstitial space and the capsule was measured from the rate of liquid displacement in the pipette. The slope of the V/S vs. Pcap linear regression was utilized to estimate the hydraulic conductivity of the Glissonian-peritoneal membrane and averaged 5.1 x 10(-3) +/- 4.7 x 10(-3) (SD) ml.h-1.cmH2O-1.cm-2 (n = 25). Hydraulic pressure in the Disse's space (Pd) was measured by closing the capsule against the transducer disconnected from the pipette. At portal and hepatic venous pressures of 7.6 +/- 2.9 and 2.6 +/- 1 cmH2O, respectively, Pd was 2.05 +/- 2 cmH2O. Physiologically, Starling pressure gradients cause fluid transfer from the sinusoids to the Disse's space; transperitoneal fluid filtration only occurs through the liver surface that faces the diaphragm, which corresponds to one-fifth of the total hepatic surface.