Complexation of Astatine(III) with Ketones: Roles of NO3- Counterion and Exploration of Possible Binding Modes.

Ketones have been proven effective in extracting astatine(III) from aqueous solvents. Previous theoretical studies suggested a mechanism where the "sp2" lone pair on the carbonyl oxygen donates electron density into the π system of the AtO+ molecular cation to form a dative-type bond. In this study, co-extraction of NO3- as AtO(NO3)·(O═CR1R2) species into the organic phase appears to be a key factor. Adjusting the electronic properties of the ketone, by having an aryl group instead of an alkyl group in the alpha position of the ketone, increased the electron density on C═O, increased the bond strength between the ketone and AtO+, and in turn increased the extraction of 211At into the organic phase. Extraction with diketones shows dependence on the bridging distance between the two carbonyl moieties, where a C3 or longer bridge results in a 10-fold increase in extraction into the organic phase. DFT calculations show the longer bridge allows for the chelation of AtO(NO3) by either the second carbonyl or the phenyl ring.

Does simulation improve clinical performance in management of postpartum hemorrhage?

BACKGROUND: Although simulation is now widely used to improve teamwork and communication, data demonstrating improvement in clinical outcomes are limited. OBJECTIVE: This study aimed to examine the clinical performance and outcomes associated with postpartum hemorrhage because of uterine atony following the implementation of a multidisciplinary simulation program. STUDY DESIGN: This was a prospective observational study of response to postpartum hemorrhage because of uterine atony in an academic medical center before (epoch 1: July 2017-June 2018) and after (epoch 2: July 2019-June 2020) implementing a multidisciplinary simulation program. A total of 22 postpartum hemorrhage simulations were performed from July 2018 to June 2019 involving more than 300 nursing, obstetrical, and anesthesia providers. The simulation program focused on managing postpartum hemorrhage events and improving teamwork and communication of the multidisciplinary teams. To evaluate the clinical effectiveness of the simulation program, the primary outcome was response to postpartum hemorrhage defined as the time from the administration of uterotonic medications to transfusion of the first unit of blood in the first 12 hours following delivery, comparing epoch 2 to epoch 1 following the implementation of a simulation program. Statistical analysis included the use of the Pearson chi-square test, Wilcoxon rank-sum test, Hodges-Lehmann statistic for differences, and bootstrap methods with a P value of <.05 considered significant. RESULTS: Between July 1, 2017, and June 30, 2018, there were 12,305 patients who delivered, of which 495 patients (4%) required transfusion. Between July 1, 2019, and June 30, 2020, there were 12,414 patients who delivered, of which 480 patients (4%) required transfusion. When isolating cases of postpartum hemorrhage because of uterine atony in both transfused groups, there were 157 women in the presimulation group (epoch 1) and 165 women in the postsimulation group (epoch 2), respectively. There was no difference in age, race, parity, or perinatal outcomes between the 2 epochs. Women in epoch 2 began receiving blood products significantly earlier in the first 12 hours following delivery compared with women in epoch 1 (51 [range, 28-125] minutes vs 102 [range, 32-320] minutes; P=.005). In addition, there was a significantly decreased variation in the time from the administration of uterotonic medications to transfusion of blood in epoch 2 (P=.035). Furthermore, women in epoch 2 had significantly lower estimated blood loss than women in epoch 1 (1250 [range, 1000-1750] mL vs 1500 [range, 1000-2000] mL; P=.032). CONCLUSION: The implementation of a multidisciplinary simulation program at a large academic center focusing on the management of postpartum hemorrhage was associated with an improved clinical response. Specifically, there were significantly faster times from the administration of uterotonic medications to transfusion of blood, decreased variance in the time from the administration of uterotonic medications to transfusion of blood, and lower estimated blood loss following the implementation of a simulation program. Because delay in treatment is a major cause of preventable maternal death in obstetrical hemorrhage, the results in our study provided clinical evidence that a simulation program may improve patient outcomes in such emergencies.

Predicting protein aggregation during storage in lyophilized solids using solid state amide hydrogen/deuterium exchange with mass spectrometric analysis (ssHDX-MS).

Solid state amide hydrogen/deuterium exchange with mass spectrometric analysis (ssHDX-MS) was used to assess the conformation of myoglobin (Mb) in lyophilized formulations, and the results correlated with the extent of aggregation during storage. Mb was colyophilized with sucrose (1:1 or 1:8 w/w), mannitol (1:1 w/w), or NaCl (1:1 w/w) or in the absence of excipients. Immediately after lyophilization, samples of each formulation were analyzed by ssHDX-MS and Fourier transform infrared spectroscopy (FTIR) to assess Mb conformation, and by dynamic light scattering (DLS) and size exclusion chromatography (SEC) to determine the extent of aggregation. The remaining samples were then placed on stability at 25 °C and 60% RH or 40 °C and 75% RH for up to 1 year, withdrawn at intervals, and analyzed for aggregate content by SEC and DLS. In ssHDX-MS of samples immediately after lyophilization (t = 0), Mb was less deuterated in solids containing sucrose (1:1 and 1:8 w/w) than in those containing mannitol (1:1 w/w), NaCl (1:1 w/w), or Mb alone. Deuterium uptake kinetics and peptide mass envelopes also indicated greater Mb structural perturbation in mannitol, NaCl, or Mb-alone samples at t = 0. The extent of deuterium incorporation and kinetic parameters related to rapidly and slowly exchanging amide pools (Nfast, Nslow), measured at t = 0, were highly correlated with the extent of aggregation on storage as measured by SEC. In contrast, the extent of aggregation was weakly correlated with FTIR band intensity and peak position measured at t = 0. The results support the use of ssHDX-MS as a formulation screening tool in developing lyophilized protein drug products.

Optimization of Iodinated Contrast Media Inventory Management: Effect of Inventory Diversification on Waste Reduction.

PURPOSE: Iodinated contrast medium (ICM) is available in single- and multiuse vials of varying sizes, but CT departments often preferentially stock only a single or a limited number of vial sizes. The aims of this study were to assess actual ICM waste at a large safety-net hospital and to compare with estimated waste if single-use vials in a variety of vial sizes or multiuse vials were used. METHODS: ICM administrations were retrospectively reviewed for all CT examinations performed in 2021 in a department that stocked only 100-mL ICM vials. Administered ICM dose, opened ICM volume and number of vials, and wasted ICM were compared with hypothetical models using optimally sized single-use vials and multiuse vials. Contrast use was also compared by patient class. RESULTS: In total, 40,393 ICM administrations over 49,670 CT examinations among 26,028 patients were reviewed, totaling 4,168,335 mL of contrast media. The mean dose was 103 mL, with mode of 100 mL. Exclusive use of 100-mL vials resulted in 1,006,165 mL waste (mean waste, 26 mL/administration). Optimally sized single-use vials resulted in 436,515 mL waste (mean waste, 11 mL/administration). Multiuse vials resulted in 537,074 mL waste (mean waste, 13 mL/administration). The distribution of optimal single-use vial size differed significantly by patient class (P < .001), with inpatient examinations more amenable to the use of smaller single-use vials. CONCLUSIONS: Optimizing ICM inventory can reduce contrast waste by 50% to 59%. Regular monitoring of contrast use may help optimize inventory selection across care settings. This retrospective review supports scrutiny of ICM inventory management to reduce waste, save costs, and mitigate the impacts of supply-chain disruptions.

Production, isolation, and shipment of clinically relevant quantities of astatine-211: A simple and efficient approach to increasing supply.

The alpha emitter astatine-211 (211At) is a promising candidate for cancer treatment based on Targeted Alpha (α) Therapy (TAT). A small number of facilities, distributed across the United States, are capable of accelerating α-particle beams to produce 211At. However, challenges remain regarding strategic methods for shipping 211At in a form adaptable to advanced radiochemistry reactions and other uses of the radioisotope. PURPOSE: Our method allows shipment of 211At in various quantities in a form convenient for further radiochemistry. PROCEDURES: For this study, a 3-octanone impregnated Amberchrom CG300M resin bed in a column cartridge was used to separate 211At from the bismuth matrix on site at the production accelerator (Texas A&M) in preparation for shipping. Aliquots of 6 M HNO3 containing up to ≈2.22 GBq of 211At from the dissolved target were successfully loaded and retained on columns. Exempt packages (<370 MBq) were shipped to a destination radiochemistry facility, University of Texas MD Anderson Cancer Center, in the form of a convenient air-dried column. Type A packages have been shipped overnight to University of Alabama at Birmingham. MAIN FINDINGS: Air-dried column hold times of various lengths did not inhibit simple and efficient recovery of 211At. Solution eluted from the column was sufficiently high in specific activity to successfully radiolabel a model compound, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1), with 211At. The method to prepare and ship 211At described in this manuscript has also been used to ship larger quantities of 211At a greater distance to University of Alabama at Birmingham. PRINCIPAL CONCLUSIONS: The successful proof of this method paves the way for the distribution of 211At from Texas A&M University to research institutions and clinical oncology centers in Texas and elsewhere. Use of this simple method at other facilities has the potential increase the overall availability of 211At for preclinical and clinical studies.

Posttraumatic nuchal pseudolipoma in a high school athlete after weight training.

Pseudolipomas are an uncommon clinical manifestation appearing as a non-encapsulated prominence of subcutaneous fat on MRI. Post-traumatic pseudolipomas (PTLs) are thought to arise from neoadipogenesis following acute or chronic trauma. These are most commonly located on the lower extremities, gluteal, and trochanteric regions. Here, we report a case of PTL in a high school athlete, arising in the posterior neck after weight training with performing barbell squats without neck padding. To our knowledge, this case represents a novel association between PTLs and weight training exercises.

Resuscitation with 100%, compared with 21%, oxygen following brief, repeated periods of apnea can protect vulnerable neonatal brain regions from apoptotic injury.

PURPOSE: To determine the effect of repeated intermittent apnea and resuscitation with 100% vs. 21% oxygen enriched gas on levels of key regulatory proteins contributing to cell death (Bax, Caspase-3) or protecting neurons from hypoxic/ischemic injury (Bcl-2, p-Akt, p-CREB). METHODS: The anaesthetized, mechanically ventilated newborn piglets underwent 10 episodes of apnea with resuscitation either with 100% or with 21% oxygen. Following 6h recovery the animals were sacrificed painlessly, the brain dissected out and used to determine levels of Bcl-2, Bax, Caspase-3, p-Akt and p-CREB in the striatum, frontal cortex, midbrain and hippocampus were studied. RESULTS: In hippocampus and striatum, Bcl-2 expression was higher with 100% vs. 21% group (173+/-29% vs. 121+/-31%, p<0.05 and 189+/-10% vs. 117+/-47%, p<0.01, respectively) whereas the Bax expression was lower (88+/-3% vs. 100+/-9%, p<0.05 and 117+/-5% vs. 133+/-10%, p<0.05, respectively). Expression of Caspase-3 in the striatum, was lower with 100% vs. 21% group (197+/-35% vs. 263+/-33%, p<0.05, respectively) but not different in the hippocampus. p-Akt expression was higher with 100% vs. 21% oxygen in the hippocampus and striatum (225+/-44% vs. 108+/-35%, p<0.01 and 215+/-12% vs. 164+/-16%, p<0.01, respectively). The p-CREB expression was higher with 100% vs. 21% oxygen resuscitation in the hippocampus (217+/-41% vs. 132+/-30%, p<0.01) with no changes in striatum. Much smaller or insignificant differences between 100% vs. 21% oxygen groups were observed in the frontal cortex and midbrain, respectively. CONCLUSION: In neonatal piglet model of intermittent apnea, selectively vulnerable regions of brain (striatum and hippocampus) are better protected from apoptotic injury when resuscitation was conducted with 100%, rather than 21%, oxygen.

Brain oxygen and metabolism is dependent on the rate of low-flow cardiopulmonary bypass following circulatory arrest in newborn piglets.

OBJECTIVE: To determine the optimum rate of low-flow hypothermic cardiopulmonary bypass (LF), following circulatory arrest (DHCA) on brain oxygenation (bO(2)), extracellular dopamine (DA), phosphorylation of select neuroregulatory proteins responsible for neuronal injury, and survival following ischemic brain injury: CREB, Erk1/2, Akt, Bcl-2, and Bax. METHODS: The piglets were placed on cardiopulmonary bypass (CPB) and cooled to 18 degrees C. They were then subjected to 30 min of DHCA followed by 1h of LF at 20, 50, or 80 ml/(kg/min), rewarmed, separated from CPB, and maintained for 2h. The bO(2) was measured by quenching of phosphorescence; DA by microdialysis; phosphorylation of CREB, ERK1/2, Akt, Bcl-2, and Bax by Western blots. The results are means+/-SD for seven experiments. RESULTS: Pre-bypass bO(2) was 47.4+/-4.2 mmHg and decreased to 1.9+/-0.8 mmHg during DHCA. At the end of LF at 20, 50, and 80 ml/(kg/min), bO(2) was 11.8+/-1.6, 26+/-1.8, and 33.9+/-2.6 mmHg, respectively. The DA increased 510-fold relative to control (p<0.001) by 15 min of LF-20 with maximum increase occurring at 45 min. With LF-50, increase in DA was not statistically significant and no increase was observed when LF-80 was used. Bcl-2 immunoreactivity increased after LF-50 and LF-80 (140+/-14.5%, p<0.05 and 202+/-34%, p<0.05, respectively). Neither flow increased Bax immunoreactivity. The ratio of Bcl-2/Bax, pCREB, pAkt, pErk increased significantly with increasing the flow rate of LF. CONCLUSIONS: The protective effect of LF following DHCA on brain metabolism is dependent on the flow rate. Flow-dependent increase in pCREB, pErk1/2, pAkt, increase in Bcl-2/Bax, and decrease in DA indicated that to minimize DHCA-dependent neuronal injury, LF flow should be above 50 ml/(kg/min).

Brain oxygenation and metabolism during selective cerebral perfusion in neonates.

OBJECTIVE: To investigate the possible neuroprotective effects of selective cerebral perfusion (SCP) during deep hypothermic circulatory arrest on brain oxygenation and metabolism in newborn piglets. METHODS: Newborn piglets 2-4 days of age, anesthetized and mechanically ventilated, were used for the study. The animals were placed on cardiopulmonary bypass, cooled to 18 degrees C and put on SCP (20 ml/(kg min)) for 90 min. After rewarming, the animals were monitored through 2h of recovery. Oxygen pressure in the microvasculature of the cortex was measured by oxygen-dependent quenching of phosphorescence. The extracellular level of dopamine in striatum was measured by microdialysis and hydroxyl radicals by ortho-tyrosine levels. Levels of phosphorylated cAMP response element binding protein (pCREB) in striatal tissue were measured by Western blots using antibodies specific for phosphorylated CREB. The results are presented as mean+/-SD (p<0.05 was significant). RESULTS: Pre-bypass cortical oxygen pressure was 48.9+/-11.3 mmHg and during the first 5 min of SCP, the peak of the histogram, corrected to 18 degrees C, decreased to 11.2+/-3.8 mmHg (p<0.001) and stayed near that value to the end of bypass. The mean value for the peak of the histograms measured at the end of SCP was 8+/-3 mmHg (p<0.001). SCP completely prevented the deep hypothermic circulatory arrest-dependent increase in extracellular dopamine and hydroxyl radicals. After SCP, there was a statistically significant increase in pCREB immunoreactivity (534+/-60%) compared to the sham-operated group (100+/-63%, p<0.005). Measurements of total CREB showed that SCP did induce a statistically significant increase in CREB as compared to sham-operated animals (168+/-31%, p<0.05). CONCLUSION: SCP, as compared to DHCA, improved cortical oxygenation and prevented increases in the extracellular dopamine and hydroxyl radicals. The increase in pCREB in the striatum following SCP may contribute to improved cellular recovery after this procedure.

Analgesic utilization before and after rescheduling of hydrocodone in a large academic level 1 trauma center.

BACKGROUND: Hydrocodone-containing products were recently rescheduled from Drug Enforcement Agency (DEA) schedule III to schedule II due to concerns of abuse and misuse. These changes went into effect on October 6, 2014. OBJECTIVE: This quality improvement project involved a retrospective analysis to determine the effect of the DEA schedule change on prescribing habits of hydrocodone-containing products as well as the remaining schedule III and IV opioids, codeine (schedule III) and tramadol (schedule IV). METHODS: The authors performed a medication use evaluation at our academic level 1 trauma hospital system on outpatient use of hydrocodone-containing products, tramadol, and codeine-containing products for 6 months before and 6 months after the change to schedule II using our electronic record and pharmacy system. RESULTS: A total of 88,428 prescription orders were analyzed. Comparison of prescriptions before and after the DEA schedule changes showed hydrocodone prescriptions reduced from an average of 225.97 per day to 1.20 per day. In addition, tramadol increased from 60.04 per day to 91.85 per day and codeine from 6.81 per day to 98.94 per day. CONCLUSIONS: Our data show a very substantial decrease in utilization of hydrocodone-containing products and concomitant increase in the utilization of tramadol and codeine products at our hospital after the DEA schedule change.

Cerebral oxygenation during repetitive apnea in newborn piglets.

This study examined the effect of repetitive apnea on brain oxygen pressure in newborn piglets. Each animal was given 10 episodes of apnea, initiated by disconnecting them from the ventilator and completed by reconnecting them to the ventilation circuit. The apneic episodes were ended 30 sec after the heart rate reached the bradycardic threshold of 60 beats per min. The oxygen pressure in the microvasculature of the cortex was measured by oxygen-dependent quenching of the phosphorescence. In all experiments, the blood pressure, body temperature, and heart rate were continuously monitored. Arterial blood samples were taken throughout the experiment and the blood pH, PaO2 and PaCO2 were measured. During pre-apnea, cortical oxygen was 55.1 +/- 6.4 (SEM, n = 7) mm Hg and decreased during each apnea to 8.1 +/- 2.8 mm Hg. However, the values of cortical oxygen varied during recovery periods. Maximal oxygen levels during recovery from the first two apneic episodes were 76.8 +/- 12 mm Hg and 69.6 +/- 9 mm Hg, respectively, values higher than pre-apnea. Cortical oxygen pressure then progressively decreased following consequent apnea. In conclusion, the data show that repetitive apnea caused a progressive decrease in cortical oxygen levels in the brain of newborn piglets. This deficit in brain oxygenation can be at least partly responsible for the neurological side effects of repetitive apnea.

Tissue oxygen tension during regional low-flow perfusion in neonates.

OBJECTIVE: We examined cerebral cortical and peripheral organ tissue Po(2) values in a neonatal piglet model of regional low-flow perfusion. METHODS: Twenty-one neonatal piglets were placed on cardiopulmonary bypass, were cooled to 18 degrees C, then underwent either deep hypothermic circulatory arrest or regional low-flow perfusion at 20 or 40 mL/(kg x min) for 90 minutes. Regional low-flow perfusion was carried out by advancing the aortic cannula into the proximal innominate artery. Tissue mean Po(2) and Po(2) distribution were measured in the cerebral cortex, liver, small bowel, and skeletal muscle through the principle of oxygen-dependent quenching of phosphorescence. Measured quantities were compared by analysis of variance or the Fisher exact test. RESULTS: During regional low-flow perfusion, axillary and femoral arterial pressures, respectively, were 55 +/- 15 and 8 +/- 4 mm Hg at 40 mL/(kg x min) and 37 +/- 10 mm Hg (P =.04) and 17 +/- 5 mm Hg (P =.08) at 20 mL/(kg x min). Venous saturations were 95% +/- 6% at 40 mL/(kg x min) and 84% +/- 6% at 20 mL/(kg x min) (P =.03 at 15, 30, and 45 minutes). Cortical Po(2) was similar to prebypass values during regional low-flow perfusion at 40 mL/(kg x min) (53 +/- 5 mm Hg) but declined during reperfusion and recovery. Cortical Po(2) was lower than before bypass during low-flow perfusion at 20 mL/(kg x min) (38 +/- 7 mm Hg) but increased during reperfusion. Po(2) in liver and bowel was less than 10 mm Hg during low-flow perfusion at both 20 and 40 mL/(kg x min). Fraction of oxygen distribution with Po(2) lower than 15 mm Hg was less during perfusion at 40 mL/(kg x min) than at 20 mL/(kg x min) (P =.001). Three of 6 piglets that received a 40-mL/(kg x min) flow rate had significant upper torso edema, metabolic acidosis, and an unstable recovery period, whereas zero of 6 piglets that received a 20-mL/(kg x min) flow rate did. CONCLUSIONS: In a piglet model, regional low-flow perfusion at 20 mL/(kg x min) resulted in lower cortical tissue oxygenation but better recovery than did perfusion at 40 mL/(kg x min). Neither flow rate adequately oxygenated organs in the lower torso.

Effect of perfusion flow rate on tissue oxygenation in newborn piglets during cardiopulmonary bypass.

BACKGROUND: Our knowledge of the best perfusion flow rate to use during cardiopulmonary bypass (CPB) in order to maintain tissue oxygenation remains incomplete. The present study examined the effects of perfusion flow rate and patent ductus arteriosus (PDA) during normothermic CPB on oxygenation in several organ tissues of newborn piglets. METHODS: The experiments were performed on 12 newborn piglets: 6 with PDA ligation (PDA-L), and 6 without PDA ligation (PDA-NL). CPB was performed through the chest at 37 degrees C. During CPB, the flow rate was changed at 15-minute intervals, ranging from 100 to 250 ml/kg/min. Tissue oxygenation was measured by quenching of phosphorescence. RESULTS: For the PDA-L group, oxygen in the brain did not change significantly with changes in flow rate. In contrast, for the PDA-NL group, oxygen was dependent upon the flow rate. Statistically significant decreases in cortical oxygen were observed with flow rates below 175 ml/kg/min. Within the myocardium, liver, and intestine, there were no significant differences in the oxygen levels between the PDA-L and PDA-NL groups. In these tissues, the oxygen decreased significantly as the flow rate decreased below 150 ml/kg/min, 125 ml/kg/min, and 175 ml/kg/min, respectively. Oxygen pressure in skeletal muscle was not dependent on either PDA ligation or flow rate. CONCLUSIONS: In newborn piglets undergoing CPB, the presence of a PDA results in reduced tissue oxygenation to the brain but not to other organs. In general, perfusion flow rates of 175 ml/kg/min or greater are required in order to maintain normal oxygenation of all organs except muscle.

Comparison of low-flow cardiopulmonary bypass and circulatory arrest on brain oxygen and metabolism.

BACKGROUND: In the neonatal brain we measured oxygen (Bo(2)), extracellular striatal dopamine (DA), and striatal tissue levels of ortho-tyrosine (o-tyr) during low-flow cardiopulmonary bypass (LFCPB) or deep hypothermic circulatory arrest (DHCA) and the post-bypass recovery period. METHODS: Newborn piglets were assigned to sham (n = 6), LFCPB (n = 8), or DHCA (n = 6) groups. Animals were cooled to 18 degrees C and underwent DHCA or LFCPB (20 mL x kg(-1) x min(-1)) for 90 minutes. The Bo(2) was measured by quenching the phosphorescence, DA by microdialysis, and hydroxyl radicals by o-tyr levels. The results are presented as the mean +/- SD (p < 0.05 was significant). RESULTS: Baseline Bo(2) was between 45 to 60 mm Hg. At the end of LFCPB, Bo(2) was 10.5 +/- 1.2 mm Hg. By 5 and 30 minutes of arrest during DHCA, Bo(2) fell to 4.2 +/- 2.5 mm Hg and 1.4 +/- 0.7 mm Hg, respectively. Compared with control, extracellular DA did not change during LFCPB. During DHCA extracellular levels of DA increased, by 750-fold from baseline at 45 minutes and to a maximum of 53000-fold at 75 minutes. After 2 hours of recovery from DHCA, the o-tyr within the striatum increased about sixfold as compared with control. There was no change in o-tyr measured after LFCPB. CONCLUSIONS: In DHCA, but not LFCPB, levels of DA and o-tyr increased considerably in the striatum of piglets, a finding that may indicate the exhaustion of cellular energy levels and contribute substantially to cellular injury.

Freeze-drying simulation framework coupling product attributes and equipment capability: toward accelerating process by equipment modifications.

A physics-based model for the sublimation-transport-condensation processes occurring in pharmaceutical freeze-drying by coupling product attributes and equipment capabilities into a unified simulation framework is presented. The system-level model is used to determine the effect of operating conditions such as shelf temperature, chamber pressure, and the load size on occurrence of choking for a production-scale dryer. Several data sets corresponding to production-scale runs with a load from 120 to 485 L have been compared with simulations. A subset of data is used for calibration, whereas another data set corresponding to a load of 150 L is used for model validation. The model predictions for both the onset and extent of choking as well as for the measured product temperature agree well with the production-scale measurements. Additionally, we study the effect of resistance to vapor transport presented by the duct with a valve and a baffle in the production-scale freeze-dryer. Computation Fluid Dynamics (CFD) techniques augmented with a system-level unsteady heat and mass transfer model allow to predict dynamic process conditions taking into consideration specific dryer design. CFD modeling of flow structure in the duct presented here for a production-scale freeze-dryer quantifies the benefit of reducing the obstruction to the flow through several design modifications. It is found that the use of a combined valve-baffle system can increase vapor flow rate by a factor of 2.2. Moreover, minor design changes such as moving the baffle downstream by about 10 cm can increase the flow rate by 54%. The proposed design changes can increase drying rates, improve efficiency, and reduce cycle times due to fewer obstructions in the vapor flow path. The comprehensive simulation framework combining the system-level model and the detailed CFD computations can provide a process analytical tool for more efficient and robust freeze-drying of bio-pharmaceuticals.

Human collagen injections to reduce rectal dose during radiotherapy.

OBJECTIVES: The continuing search for interventions, which address the incidence and grade of rectal toxicities associated with radiation treatment of prostate cancer, is a major concern. We are reporting an investigational trial using human collagen to increase the distance between the prostate and anterior rectal wall, thereby decreasing the radiation dose to the rectum. METHODS: This is a pilot study evaluating the use of human collagen as a displacing agent for the rectal wall injected before starting a course of intensity-modulated radiotherapy (IMRT) for prostate cancer. Using a transperineal approach, 20 mL of human collagen was injected into the perirectal space in an outpatient setting. Computerized IMRT plans were performed pre- and postcollagen injection, and after a patient completed their radiotherapy, to determine radiation dose reduction to the rectum associated with the collagen injection. Computed tomography scans were performed 6 months and 12 months after completing their radiotherapy to evaluate absorption rate of the collagen. All patients were treated with IMRT to a dose of 75.6 Gy to the prostate. RESULTS: Eleven patients were enrolled into the study. The injection of human collagen in the outpatient setting was well tolerated. The mean separation between the prostate and anterior rectum was 12.7 mm. The mean reduction in dose to the anterior rectal wall was 50%. All men denied any rectal symptoms during the study. CONCLUSIONS: The transperineal injection of human collagen for the purpose of tissue displacement is well tolerated in the outpatient setting. The increased separation between the prostate and rectum resulted in a significant decrease in radiation dose to the rectum while receiving IMRT and was associated with no rectal toxicities.

Cerebral and somatic oxygen saturation decrease after delayed sternal closure in children after cardiac surgery.

OBJECTIVES: Delayed sternal closure after pediatric cardiac surgery can temporarily impair cardiac output. Cerebral and somatic regional oxygen saturation measured by using near-infrared spectroscopy (NIRS) have been used as potential surrogates of cerebral and somatic mixed venous oxygen saturation. We hypothesized that cerebral and somatic regional oxygen saturation correlate with indicators of hemodynamic compromise after delayed sternal closure in children undergoing cardiac surgery. METHODS: We studied 36 postoperative children (median age, 10 days; range, 1-510 days) undergoing delayed sternal closure 3.7 +/- 2 days after cardiac surgery. Twenty-five had biventricular physiology, whereas 11 had single-ventricle physiology. Cerebral regional oxygen saturation, somatic regional oxygen saturation, and other physiologic parameters (hemodynamic data, respiratory data, blood gas analysis, lactate levels, and inotrope scores) were analyzed at 16 different time points 24 hours before and after sternal closure. One-way analysis of variance and the paired t test were used for statistical comparisons. RESULTS: Cerebral and somatic regional oxygen saturation decreased after delayed sternal closure compared with preclosure levels (P = .02 and P = .01, respectively). Higher heart rate (P = .03), lactate levels (P = .02), and left atrial pressure (P = .001) were also noted, suggesting mild hemodynamic compromise. Arterial pressure and inotrope score were unchanged. Somatic regional oxygen saturation returned to preclosure levels earlier in the biventricular group than in the single-ventricle group, whereas cerebral regional oxygen saturation remained decreased after sternal closure with no evidence of return to preclosure levels during the observation period. Oxygen saturation, Pao(2), and Paco(2) levels were unaffected by sternal closure, although greater positive-pressure ventilation was required (P < .01), suggesting reduced lung compliance. CONCLUSION: Cerebral and somatic regional oxygen saturation decrease after delayed sternal closure in children recovering from congenital cardiac surgery. These indices are in agreement with other physiologic indicators of cardiac performance, suggesting mild and transient hemodynamic compromise after sternal closure. Cerebral and somatic regional oxygen saturation monitoring might be a useful adjunct during delayed sternal closure.

Association of rapid head growth in children following tracheostomy tube placement.

INTRODUCTION: Our clinical observation indicates that some children who have a tracheostomy may experience increasing head circumference as they grow and develop. Accurate assessment and interpretation of growth parameters is an essential component of following child development. Appreciation for variations in growth is especially important in special populations, such as children with a tracheostomy. The aim of this study is to define head growth in children with a tracheostomy. METHOD: This retrospective cohort study includes children who underwent tracheostomy tube placement prior to 2 years of age in a respiratory rehabilitation unit within a children's hospital. Serial head circumference measurements were plotted against age on growth charts adjusted for gestational age. The percentage of patients with accelerated head growth, defined as increased head circumference across two major percentiles within 6 months following tracheostomy, was determined. RESULTS: Fifty-seven percent (20 out of 35 children) demonstrated increased head circumference across two major percentiles within 6 months following tracheostomy. DISCUSSION: Accelerated head growth is associated with the presence of a tracheostomy tube in children in this study. Further investigation is warranted to establish the relationship of head circumference to other growth parameters. In addition, the etiology of this phenomenon requires additional study. Understanding head growth in children with a tracheostomy will promote adequate growth assessment and may lead to improved patient care.

A second-generation cementless total hip arthroplasty mean 9-year results.

Two hundred fifty-eight primary total hip arthroplasties in 231 patients were implanted using a circumferentially, proximally porous-coated, collared femoral component and a cementless, hemispherical, porous-coated acetabular component and followed up for a mean of 9 years (5-14 years). Four femoral components were revised (2 stems for infection and 2 stems for aseptic loosening). One additional femoral component was radiographically loose at last follow-up. Nine hips underwent acetabular revision (4 for instability, 2 for infection, 2 for loosening, and 1 for osteolysis). Ten-year survivorship with revision or loosening of any component as the end point was 92%; with femoral component aseptic loosening as end point, survivorship was 98%; with acetabular aseptic loosening as the end point, survivorship was 99%. Osteolysis was identified in 26 hips (13%).