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Background : Esophageal Doppler monitoring (EDM) is utilized in numerous clinical settings. This study examines the relationship between pulmonary artery catheter (PAC) and EDM-derived hemodynamic parameters, concentrating on gender- and age-related EDM measurement biases. Materials and Methods : Prospective study of EDM use in ventilated surgical ICU patients. Parameters examined included demographics, diagnosis, resuscitation endpoints, cardiac output (CO) and stroke volume from both devices, number of personnel and time needed to place equipment, time to data acquisition, duration of use, complications of placement. Results : Fifteen patients (11 men, 4 women, mean age 47 years) were included. Most common diagnoses included trauma (7/15) and sepsis (4/15). Insertion time and time to data acquisition were shorter for EDM than for PAC ( P < 0.001). The EDM required an average of 1.1 persons to place (2.4 for PAC, P =0.002). Mean EDM utilization time was 12.4 h. There was a fair CO correlation between EDM and PAC (r = 0.647, P < 0.001). Overall, the EDM underestimated CO relative to PAC (bias -1.42 ± 2.08, 95% CI: -5.58-2.74), with more underestimation in women (mean bias difference of -1.16, P < 0.001). No significant age-related measurement bias differences between PAC and EDM were noted. Significant reductions in lactate and norepinephrine requirement were noted following EDM monitoring periods. Conclusions : This study found that the EDM significantly underestimated cardiac output in women when compared to PAC. Clinicians should be aware of this measurement bias when making therapeutic decision based on EDM data. Significant reductions in lactate and norepinephrine requirement during EDM monitoring periods support the clinical usefulness of EDM technology.

Background: The Lancet Commission on Global Surgery (LCoGS) surgical indicators have given the surgical community metrics for objectively characterizing the disparity in access to surgical healthcare. However, aggregate national statistics lack sufficient specificity to inform strengthening plans at the community level. We performed a second-stage analysis of Colombian surgical system service delivery to inform the development of resource- and context-sensitive interventions to inform a revision of the Decennial Public Health Plan for access inequity resolution., Methods: Data from the year 2016 to inform total operative volume (TOV) and 30-day non-risk adjusted peri-operative mortality (POMR) were collected from the Colombian national health information system. TOV and POMR were sub-characterized by demographics, urgency, service line, disease pathology and facility location., Findings: In 2016, aggregate national mortality was 0·87%, while mortality attributable to elective and emergency surgery was 0·73% and 1·30%, respectively. The elderly experienced a 5·6-fold higher mortality, with 4·2% undergoing an operation within 30 days of dying. Individuals undergoing hepatobiliary, thoracic, cardiac, and neurosurgical operations experienced the highest mortality rates while obstetrics, general surgery, orthopaedics, and urology performed the largest procedure volume. Finally, analysis of operation and service line specific POMR reveals opportunities for improvement., Interpretation: This granular second-stage analysis provides actionable data which is fundamental to the development of resource and context-sensitive interventions to address gaps and inequities in surgical system service delivery. Furthermore, this analysis validates the modeling underlying development of the LCoGS indicators. These data will inform the assessment of implementation priorities and revision of the Colombian Decennial Public Health Plan., Funding: None., Competing Interests: AFGS has nothing to disclose; GEHA has nothing to disclose; DT has nothing to disclose; DB has nothing to disclose; LLC has nothing to disclose; RENR has nothing to disclose; RR has nothing to disclose; VG has nothing to disclose; JSH has nothing to disclose., (© 2022 The Author(s).)

Background: Surgical, anaesthetic, and obstetric (SAO) health-care system strengthening is needed to address the emergency and essential surgical care that approximately 5 billion individuals lack globally. To our knowledge, a complete, non-modelled national situational analysis based on the Lancet Commission on Global Surgery surgical indicators has not been done. We aimed to undertake a complete situation analysis of SAO system preparedness, service delivery, and financial risk protection using the core surgical indicators proposed by the Commission in Colombia, an upper-middle-income country., Methods: Data to inform the six core surgical system indicators were abstracted from the Colombian national health information system and the most recent national health survey done in 2007. Geographical access to a Bellwether hospital (defined as a hospital capable of providing essential and emergency surgery) within 2 h was assessed by determining 2 h drive time boundaries around Bellwether facilities and the population within and outside these boundaries. Physical 2 h access to a Bellwether was determined by the presence of a motor vehicle suitable for individual transportation. The Department Administrativo Nacional de Estadística population projection for 2016 and 2018 was used to calculate the SAO provider density. Total operative volume was calculated for 2016 and expressed nationally per 100 000 population. The total number of postoperative deaths that occurred within 30 days of a procedure was divided by the total operative volume to calculate the all-cause, non-risk-adjusted postoperative mortality. The proportion of the population subject to impoverishing costs was calculated by subtracting the baseline number of impoverished individuals from those who fell below the poverty line once out-of-pocket payments were accounted for. Individuals who incurred out-of-pocket payments that were more than 10% of their annual household income were considered to have experienced catastrophic expenditure. Using GIS mapping, SAO system preparedness, service delivery, and cost protection were also contextualised by socioeconomic status., Findings: In 2016, at least 7·1 million people (15·1% of the population) in Colombia did not have geographical access to SAO services within a 2 h driving distance. SAO provider density falls short of the Commission's minimum target of 20 providers per 100 000 population, at an estimated density of 13·7 essential SAO health-care providers per 100 000 population in 2018. Lower socioeconomic status of a municipality, as indicated by proportion of people enrolled in the subsidised insurance regime, was associated with a smaller proportion of the population in the municipality being within 2 h of a Bellwether facility, and the most socioeconomically disadvantaged municipalities often had no SAO providers. Furthermore, Colombian providers appear to be working at or beyond capacity, doing 2690-3090 procedures per 100 000 population annually, but they have maintained a relatively low median postoperative mortality of 0·74% (IQR 0·48-0·84). Finally, out-of-pocket expenses for indirect health-care costs were a key barrier to accessing surgical care, prompting 3·1 million (6·4% of the population) individuals to become impoverished and 9·5 million (19·4% of the population) individuals to incur catastrophic expenditures in 2007., Interpretation: We did a non-modelled, indicator-based situation analysis of the Colombian SAO system, finding that it has not yet met, but is working towards achieving, the targets set by the Lancet Commission on Global Surgery. The observed interdependence of these indicators and correlation with socioeconomic status are consistent with well recognised factors and outcomes of social, health, and health-care inequity. The internal consistency observed in Colombia's situation analysis validates the use of the indicators and has now informed development of an early national SAO plan in Colombia, to set a data-informed stage for implementation and evaluation of timely, safe, and affordable SAO health care, within the National Public Health Decennial Plan, which is due in 2022., Funding: Zoll Medical., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To describe quality of life (QoL) in the year following minor injury and to test the hypothesis that individuals with depression in the postinjury year experience lower QoL than do individuals with no depression., Design: Prospective, longitudinal, cohort design. A total of 275 adults were randomly selected from injured patients presenting to an urban emergency department., Methods: All participants underwent structured psychiatric diagnostic interviews immediately after injury and at 3, 6, and 12 months. The primary outcome, QoL, was measured using the Quality of Life Index. Covariates included demographics, injury status, preinjury functional status, preinjury social support, and anticipation of problems postdischarge. The General Estimating Equation was used to compare changes in QoL between participants with and without depression over 3, 6, and 12 months, adjusting for covariates., Results: An 18.1% proportion (95% confidence interval [CI] 13.3, 22.9%) of the sample met criteria for a mood disorder in the postinjury year. The depressed group reported a QoL that was 4.2 points (95% CI 2.8-5.6) lower in the year postinjury compared with that of the nondepressed group., Conclusions: Depression after minor injury negatively affects QoL even a full year postinjury., Clinical Relevance: The findings of this study show that patients who have injuries that are treated and discharged from an emergency department can have significantly lower QoL in the year after that injury that is attributed, in part, to postinjury depression. Nurses should provide anticipatory guidance to patients that they may experience feelings of sadness or being "blue," and that if they do, they should seek care., (© 2013 Sigma Theta Tau International.)

Objective: In this study, available medical literature were reviewed to determine whether brain hypoxia as measured by brain tissue oxygen (Bto2) levels is associated with increased risk of poor outcome after traumatic brain injury (TBI). A secondary objective was to examine the safety profile of a direct BtO2 probe. DATA SOURCE AND EXTRACTION: Clinical studies published between 1993 and 2008 were identified from electronic databases, Index Medicus, bibliographies of pertinent articles, and expert consultation. The following inclusion criteria were applied for outcome analysis: 1) more than 10 patients described, 2) use of a direct Bto2 monitor, 3) brain hypoxia defined as Bto2 <10 mm Hg for >15 or 30 minutes, 4) 6-month outcome data, and 5) clear reporting of patient outcome associated with Bto2. For the analysis, each selected article had to have adequate data to determine odds ratios (ORs) and confidence intervals (CIs). Thirteen studies met the initial inclusion criteria and three were included in the final outcome analysis. Safety data were abstracted from any report where it was mentioned., Data Synthesis: The three studies included 150 evaluable patients with severe TBI (Glasgow Coma Scale 15 minutes) was associated with worse outcome (OR 4.0; 95% CI 1.9-8.2) and increased mortality (OR 4.6; 95% CI 2.2-9.6). We reviewed published safety data; in 292 patients monitored with a Bto2 probe, only two adverse events were reported., Conclusion: Summary results indicate that brain hypoxia (<10 mm Hg) is associated with worse outcome after severe TBI and that Bto2 probes are safe. These results imply that treating patients to increase Bto2 may improve outcome after severe TBI. This question will require further study.

Halosalicylamide derivatives were identified from high-throughput screening as potent inhibitors of HCV NS5B polymerase. The subsequent structure and activity relationship revealed the absolute requirement of the salicylamide moiety for optimum activity. Methylation of either the hydroxyl group or the amide group of the salicylamide moiety abolished the activity while the substitutions on both phenyl rings are acceptable. The halosalicylamide derivatives were shown to be non-competitive with respect to elongation nucleotide and demonstrated broad genotype activity against genotype 1-3 HCV NS5B polymerases. Inhibitor competition studies indicated an additive binding mode to the initiation pocket that is occupied by the thiadiazine class of compounds and an additive binding mode to the elongation pocket that is occupied by diketoacids, but a mutually exclusive binding mode with respect to the allosteric thumb pocket that is occupied by the benzimidazole class of inhibitors. Therefore, halosalicylamides represent a novel class of allosteric inhibitors of HCV NS5B polymerase.

We report the discovery of the pyrimido-diazepine scaffolds as novel adenine mimics. Structure-based design led to the discovery of analogs with potent inhibitory activity against receptor tyrosine kinases, such as KDR, Flt3 and c-Kit. Compound 14 exhibited low nanomolar KDR enzymatic and cellular potencies (IC(50)=9 and 52 nM, respectively).

Bicyclic iminium ethers can be synthesized by the reactions of ketones with hydroxyalkyl azides. These cationic species react with a variety of nucleophiles via two possible pathways. The initially formed, kinetic product arises from direct addition to the iminium carbon in the substrate. In some cases, the initial adduct reverts to the starting iminium ether and the ultimate product arises from nucleophilic displacement at the O-alkyl group to afford the terminally functionalized N-substituted amide. The behavior of a range of nucleophiles was studied by using several iminium ethers. In general, the relevant pathway could be identified by characterization of the product formed. For hydroxide addition, which can afford only one product regardless of mechanism, the reaction was shown to arise by the kinetic pathway, using (18)O-labeled hydroxide. A one-pot synthesis of functionalized lactams entailing treatment of ketones first with hydroxyalkyl azides followed by nucleophilic addition was also developed.

Background: As the malpractice and financial environment has changed, injured patients evaluated by the trauma team and discharged from the emergency department (ED) are now commonplace. The evaluation, care, and disposition of this population has become a significant workload component but is not reported to accrediting organizations and is relatively invisible to hospital administrators. Our objective was to quantify and begin to qualify the evolving picture of the trauma ED discharge population as a work component of trauma service function in an urban, Level I trauma center with an aeromedical program., Methods: Trauma registry (contacts, mechanism, transport, injuries, and disposition) and hospital databases (ED closure, occupancy rates) were queried for a 5-year period (1999-2003). Trend analysis provided statistical comparisons for questions of interest., Results: During the 5-year study period, the total number of trauma contacts rose by 18.1% (2,220 in 1999 vs. 2,622 in 2003; trend p < 0.05). This increase in total contacts was not a manifestation of an increase in admissions (1,672 in 1999 vs. 1,544 in 2003) but rather a reflection of a marked increase in patients seen primarily by the trauma team and discharged from the ED (473 in 1999 vs. 1,000 in 2003; trend p < 0.05). These ED discharge patients were increasingly transported by helicopter (12.3% in 1999 vs. 29.2% in 2003; trend p < 0.05) and less frequently from urban areas (57.1% in 1999 vs. 48.1% in 2003; trend p < 0.05) over the course of the study period. Average injury severity of this group increased over the study period (Injury Severity Score of 2.7 +/- 0.1 in 1999 vs. 3.3 +/- 0.1 in 2003; trend p < 0.05). ED length of stay for this group increased 19.8% over the study period (trend p < 0.05), averaging nearly 5 hours in 2003., Conclusion: The total number, relative percentage, and injury severity of patients evaluated by the trauma team and discharged from the ED has significantly increased over the last 5 years, representing nearly 5,000 patient care hours in 2003. Systems to care for these patients in a cost- and resource-efficient fashion should be put in place. The impact of this growing population of patients on the workload of the trauma center should be recognized by accrediting agencies, hospital administration, and Emergency Medical Services.

The application of two nitrogen ring expansion reactions to lasubine alkaloid synthesis is reported. The approach involves a conjugate reduction/alkylation sequence carried out on triisopropylsilyl-protected (S)-4-(-)-hydroxycyclopentenone, the formation of the quinolizidone ring system through nitrogen ring expansion, and the addition of an arylmetallic species to the resulting lactam. This work resulted in the preparation of 2-epi-lasubine II and a formal synthesis of lasubine II. [reaction: see text]

An asymmetric equivalent of the Schmidt reaction permits stereocontrol in ring expansions of symmetrical cyclohexanones. The procedure involves the reaction of chiral 1,2- and 1,3-hydroxyalkyl azides with ketones under acid catalysis; the initial reaction affords an iminium ether that can be subsequently opened with base. A systematic study of this reaction is reported, in which ketone substrates, chiral hydroxyalkyl azides, and reaction conditions are varied. Selectivities as high as ca. 98:2 are possible for the synthesis of substituted caprolactams, with up to 1,7-stereoselection involved in the overall process. The fact that either possible migrating carbon is electronically identical provides an unusual opportunity to study a ring-expansion reaction controlled entirely by stereoelectronic factors. The mechanism of the reaction and the source of its stereoselectivity are also discussed.

Hypothesis: Penetrating neck trauma has traditionally been evaluated by surgical exploration and/or invasive diagnostic studies. We hypothesized that computed tomography (CT), used as an early diagnostic tool to accurately determine trajectory, would direct or eliminate further studies or procedures in stable patients with penetrating neck trauma., Design: Retrospective case series., Setting: Academic, urban, level I trauma center., Patients: Hemodynamically stable patients without hard signs of vascular injury or aerodigestive violation who had sustained penetrating trauma to the neck., Interventions: Patients underwent a spiral CT as an initial diagnostic study after initial evaluation in the trauma bay. Further invasive studies were directed by CT findings., Main Outcome Measures: Number of invasive studies performed., Results: Twenty-three patients were identified during the 30-month period. Nineteen patients sustained gunshot wounds; 3, shotgun wounds; and 1, a stab wound. One patient died of a cranial gunshot wound. Three isolated zone I, 1 isolated zone II, 9 isolated zone III, and 10 multiple neck zone trajectories were evaluated. Thirteen patients were identified by CT to have trajectories remote from vital structures and required no further evaluation. Ten patients underwent angiography. Only 2 underwent bronchoscopy and esophagoscopy. Four patients were discharged from the emergency department; 7 other patients were discharged within 24 hours. No adverse patient events occurred before, during, or after CT scan., Conclusions: Computed tomography in stable selected patients with penetrating neck trauma appears safe. Invasive studies can often be eliminated from the diagnostic algorithm when CT demonstrates trajectories remote from vital structures. As a result, efficient evaluation and early discharge from the trauma bay or emergency department can be realized. Further prospective study of CT scan after penetrating neck trauma is needed.

Objective: Damage control (DC) has proven valuable in exsanguinated patients. The purpose of this study was to quantify and qualify the impact of current damage control principles applied in a penetrating abdominal injury (PAI) population., Methods: Over a 3-year period (June 1997-May 2000), of 271 laparotomies for PAI, 24 patients underwent DC (8.9%). Demographics, injury grade, resuscitative and operative parameters, acid-base status, coagulation profiles, fluid/transfusion requirements, definitive repairs, abdominal closure, complications, and outcomes were reviewed. Data were compared with our DC experience a decade earlier. Fisher's exact test was used for comparisons., Results: Overall survival improved for equivalent Injury Severity Score, Revised Trauma Score, TRISS, admission systolic blood pressure, operating room systolic blood pressure, and Penetrating Abdominal Trauma Index score. Solids (1.2 vs. 1.3), hollow organ (1.5 vs. 1.7), and major vascular injuries (0.5 vs. 0.8) per patient remain unchanged. Currently, there was less hypothermia with equivalent operating room times. In intensive care unit survivors, acid-base status was similar but coagulopathy and hypothermia were less severe. Definitive colon management has shifted from ostomies to anastomoses. Eventual fascial closure occurred in 14 of 19 (74%) compared with 12 of 14 (86%) in the historical group. There were three gastrointestinal fistulae (one pancreatic), one anastomotic leak, and three intra-abdominal abscesses., Conclusion: Continued application of DC principles has led to improved survival with PAI. Better control of temperature, experience with the open abdomen, and intensive care unit care may be causative.

Focused Abdominal Sonogram for Trauma (FAST) examination is being used increasingly for the torso evaluation of injured patients. In a controlled setting using peritoneal dialysis patients as models for injured patients with free fluid we hypothesized that more experienced providers would perform FAST with greater accuracy. Twelve fellow or attending level trauma surgeons, two radiologists, and one ultrasound technician were studied for their ability to detect intraperitoneal fluid (0-1600 cm3) in nine peritoneal dialysis patients with two different volumes of dialysate/patient. FAST experience with injured patients was defined as minimal (<30 patients examinations), moderate (30-100), or extensive (>100). All surgeons had participated in a didactic/practical course before the study. Test results were reported as "+" or "-" by the participant; "+" results were further quantified by volume. The sensitivity of those in the minimal-, moderate-, and extensive-experience to detect <1 L was 45, 87, and 100 per cent, respectively; the accuracy in detecting dialysate volume within 250 cm3 was 38, 63, and 90 per cent, respectively. In this controlled setting the accuracy of FAST particularly in diagnosing smaller volumes, as well as the ability to quantify volume, improves with experience. The learning curve for FAST starts to flatten out at 30 to 100 examinations. Training and credentialing policies should consider these findings to optimize patient care.

The regiochemistry of ring expansions of 2-substituted cyclic ketones using 1,2-azidoethanol and 1,3-azidopropanol was examined. It was determined that the reactions of ketones with an adjacent methyl or ethyl group are generally unselective, but that bulkier substituents lead to preferential migration of the more highly substituted carbon. In addition, it was found that ketones bearing inductively electron-withdrawing substituents (OMe, Ph, Br) undergo selective migration of the less highly substituted carbon. For some substrates, alternative reaction pathways were also identified.

No other part of critical care evaluation is more challenging than the monitoring of end-organ function. Defining the endpoints of resuscitation using organ function is complex and controversial. Although replete with opinions and data, the observation of cardiac, renal, and hepatic function and the technical ability to categorize organ performance is crucial to providing adequate intensive care resuscitation and monitoring.

Despite literature showing safety, accuracy, and therapeutic capability of emergency colonoscopy for acute lower gastrointestinal (LGI) bleeding, surgical literature suggests that this examination is difficult to perform in the acute setting. In contrast to currently accepted protocols, we believe that unprepared colonoscopy within 24 hours of presentation can be performed safely with a high rate of success in localizing and often treating the specific cause of LGI bleeding. We report results over a 7-year period in our institution using early colonoscopy as the primary investigative method for the diagnosis and treatment of LGI bleeding. We analyzed 85 consecutive patients suspected of LGI bleeding referred to the surgical service between 1989 and 1996. LGI bleeding was defined as the passage of blood per rectum, distal to the ligament if Trietz. We excluded patients who were only hemoccult positive or had an upper gastrointestinal source by nasogastric aspirate or upper gastrointestinal endoscopy. All patients underwent urgent unprepped colonoscopy by surgical endoscopists relying on the cathartic effect of blood and liberal suction/irrigation to cleanse the colon. Therapeutic maneuvers included Nd:YAG laser or BICAP coagulation. Studies in which active bleeding was found or lesions with endoscopic evidence of recent hemorrhage were considered positive. A total of 126 colonoscopies were performed in 85 patients, 44 males and 41 females, with a median age of 75 years (range, 12-91 years). Fifty-three patients (62%) had hematocrit drops of greater than 5 per cent. Thirty-four patients were transfused an average of 4.5 units of blood per patient. The source of bleeding was correctly identified in 82 of 85 (97%) patients. Ninety-one per cent of sources were colonic, and 9 per cent were small bowel. Fecal residue prevented initial adequate examination in only two patients. Diverticulosis (20%), ischemic colitis (18%), hemorrhoids (14%), and arteriovenous malformations (11%) were the predominant sources of bleeding. Spontaneous cessation of bleeding occurred in 58 (68%) patients. Control of active hemorrhage was achieved endoscopically in 17 of 27 acutely bleeding patients. Significant therapeutic interventions were performed in 26 additional patients, including fulgration, polypectomy, relief of obstruction, and removal of foreign body. One patient with asymptomatic free air was observed nonoperatively, for a complication rate of 0.8 per cent. In-hospital mortality was 3.5 per cent (three patients), all secondary to multisystem organ failure and underlying disease. In-hospital rebleeding rate was 3.5 per cent (three). We conclude that, using colonoscopy, it is possible to identify the source of acute LGI bleeding in more than 95 per cent of cases. Diagnostic and therapeutic capability with colonoscopic intervention to control active hemorrhage is especially appealing. Additionally, the pattern, amount, and location of blood in the unprepared colon all give clues as to source and rate of bleeding. In experienced hands, morbidity and mortality of emergent colonoscopy is very low. High accuracy, safety, and therapeutic capability makes colonoscopy the initial diagnostic test of choice for acute LGI hemorrhage.