William H. Frawley

Allogeneic blood transfusion increases the risk of postoperative bacterial infection: A meta-analysis

Background: Immunosuppression is a consequence of allogeneic (homologous) blood transfusion (ABT) in humans and is associated with an increased risk in cancer recurrence rates after potentially curative surgery as well as an increase in the frequency of postoperative bacterial infections. Although a meta-analysis has been reported demonstrating the relationship between ABT and colon cancer recurrence, no meta-analysis has been reported demonstrating the relationship of ABT to postoperative bacterial infection. Methods: Twenty peer-reviewed articles published from 1986 to 2000 were included in a meta-analysis. Criteria for inclusion included a clearly defined control group (nontransfused) compared with a treated (transfused) group and statistical analysis of accumulated data that included stepwise multivariate logistic regression analysis. In addition, a subgroup of publications that included only the traumatically injured patient was included in a separate meta-analysis. A fixed effects analysis was conducted with odds ratios obtained by using the conditional maximum likelihood method and 95% confidence intervals on the obtained odds ratios were determined using the mid-p technique. Results: The total number of subjects included in this meta-analysis was 13,152 (5,215 in the transfused group and 7,937 in the nontransfused group). The common odds ratio for all articles included in this meta-analysis evaluating the association of ABT to the incidence of postoperative bacterial infection was 3.45 (range, 1.43-15.15), with 17 of the 20 studies demonstrating a value of p < or = 0.05. These results provide overwhelming evidence that ABT is associated with a significantly increased risk of postoperative bacterial infection in the surgical patient. The common odds ratio of the subgroup of trauma patients was 5.263 (range, 5.03-5.43), with all studies showing a value of p < 0.05 (0.005-0.0001). These results demonstrate that ABT is associated with a greater risk of postoperative bacterial infection in the trauma patient when compared with those patients receiving ABT during or after elective surgery. Conclusion: These results demonstrate that ABT is an associated and apparently significant and frequently overlooked risk factor for the development of postoperative bacterial infection in the surgical patient. Allogeneic blood transfusion is a greater risk factor in the traumatically injured patient when compared with the elective surgical patient for the development of postoperative bacterial infection.

Pelvic ring disruptions: Prediction of associated injuries, transfusion requirement, pelvic arteriography, complications, and mortality

Objective To determine if age, fracture pattern, systolic blood pressure on arrival, base deficit, or the Revised Trauma Score is predictive of mortality, transfusion requirements, use of pelvic arteriography, later complications, or injuries associated with the pelvic ring disruption. Study Design Retrospective review of a prospectively collected database. Methods All closed pelvic ring disruptions seen between November 1, 1997 and November 30, 1999 were included. Predictive variables and outcome variables were recorded for each patient. Statistical analysis was used to determine if the above variables were predictive. Results Shock on arrival and the Revised Trauma Score were significantly associated with mortality, transfusion requirement, Injury Severity Score, and all the Abbreviated Injury Scores except the one for skin. In addition, the Revised Trauma Score was significantly associated with the use of pelvic arteriography and predicted more complications than did shock on arrival. Age was significantly associated with transfusion requirement, Injury Severity Score, the chest and skin Abbreviated Injury Scores, use of arteriography, and death. The mortality rate among patients who presented in shock was 57 percent. A Revised Trauma Score of less than 11 predicted mortality with a sensitivity and specificity of 58 percent and 92 percent, respectively. Shock on arrival predicted mortality with a sensitivity and specificity of 27 percent and 96 percent, respectively. Age greater than sixty years predicted mortality with a sensitivity and specificity of 26 percent and 91 percent, respectively. In our analysis of the fracture patterns, we were unable to demonstrate consistent, meaningful links between specific fracture classes and the outcome variables. Conclusions Shock on arrival and the Revised Trauma Score are useful predictors of mortality and transfusion requirements, Injury Severity Score, and Abbreviated Injury Scores for the head and neck, face, chest, abdomen, and extremities. In addition, the Revised Trauma Score predicts the use of pelvic arteriography and later complications. Age predicted transfusion requirement, Injury Severity Score, the chest and skin Abbreviated Injury Scores, use of arteriography, and death.

Laparoscopic skills training

BACKGROUND The purpose of this study was to quantify the learning curve of a previously validated laparoscopic skills curriculum. METHODS Second-year medical students (MS2, n = 11) and second (PGY2, n = 11) and third (PGY3, n = 6) year surgery residents were enrolled into a curriculum using five video-trainer tasks. All subjects underwent baseline testing, training (30 minutes per day for 10 days), and final testing. Scores were based on completion time. The relationship between task completion time and the number of practice repetitions was examined. Improvement (the difference in baseline and final performance) amongst groups was compared by one-way analysis of variance using the baseline score as a covariate; P <0.05 indicated significance. RESULTS Baseline scores were not significantly different. Final scores were significantly better for MS2s versus PGY3s. Adjusted-improvement was significantly larger for the MS2s compared with PGY2s and PGY3s, and for PGY2s compared with PGY3s. The mean number of repetitions corresponding to a predicted 90th percentile score was 32. CONCLUSION Inexperienced subjects benefit the most from skills training. For maximal benefit, we recommend that each task be practiced for at least 30 to 35 repetitions.

Tremor response to polarity, voltage, pulsewidth and frequency of thalamic stimulation

Background: Thalamic deep brain stimulation ameliorates essential and parkinsonian tremors refractory to medications. Stimulus voltage, polarity configuration, frequency, and pulsewidth can each be adjusted in order to optimize tremor control and maximize battery life. The relative impacts of these programmable variables have not previously been quantified. Methods: The thalamus of 11 patients (bilaterally in 2) was studied 4 to 59 months postoperatively. The stimulator was inactivated and medications withheld for 12 hours, and optimal electrode contacts were selected. Stimulation followed at a range of voltages (0, 1, 2, 3, or 4 V), pulsewidths (60, 90, or 120 μs), and frequencies (130, 160, or 185 Hz) for both monopolar and bipolar configurations. Seventy-eight combinations of variables were programmed in random sequence. Postural and action tremors were measured with an electromagnetic tracker, tremor was subjectively graded, and side effects were noted. Results: Voltage was consistently predictive of tremor response. Mean postural tremor amplitude in PD fell from 6.4 cm at 0 V to 2.6, 1.0, 0.3, and 0 cm at 1 through 4 V (bipolar configuration). The voltage response curve for essential tremor was flatter. The monopolar configuration was 10 to 25% more effective than bipolar. The longest pulsewidth tested was up to 30% more effective than the shortest, but frequency changes had little effect on tremor amplitude. Side effects occurred only with monopolar stimulation, and the only setting that was intolerable for the majority was 4 V, 120 μs, and 185 Hz. Conclusion: Bipolar deep brain stimulation at 90 μs, 130 Hz, adjusting the voltage up to 3 V, tends to be effective and well tolerated. Monopolar provides similar benefits for lower voltage, but side effects become common at 3 or 4 V.

Quantitative oculographic characterisation of internuclear ophthalmoparesis in multiple sclerosis: the versional dysconjugacy index Z score

Background: There is a poor correlation between multiple sclerosis disease activity, as measured by magnetic resonance imaging, and clinical disability. Objective: To establish oculographic criteria for the diagnosis and severity of internuclear ophthalmoparesis (INO), so that future studies can link the severity of ocular dysconjugacy with neuroradiological abnormalities within the dorsomedial brain stem tegmentum. Methods: The study involved 58 patients with multiple sclerosis and chronic INO and 40 normal subjects. Two dimensional infrared oculography was used to derive the versional dysconjugacy index (VDI)—the ratio of abducting to adducting eye movements for peak velocity and acceleration. Diagnostic criteria for the diagnosis and severity of INO were derived using a Z score and histogram analysis, which allowed comparisons of the VDI from multiple sclerosis patients and from a control population. Results: For a given saccade, the VDI was typically higher for acceleration v velocity, whereas the Z scores for velocity measures were always higher than values derived from comparable acceleration VDI measures; this was related to the greater variability of acceleration measures. Thus velocity was a more reliable measure from which to determine Z scores and thereby the criteria for INO and its level of severity. The mean (SD) value of the VDI velocity derived from 40 control subjects was 0.922 (0.072). The highest VDI for velocity from a normal control subject was 1.09, which was 2.33 SD above the normal control mean VDI. We therefore chose 2 SD beyond this value (that is, a Z score of 4.33) as the minimum criterion for the oculographic confirmation of INO. Of patients thought to have unilateral INO on clinical grounds, 70% (16/23) were found to have bilateral INO on oculographic assessment. Conclusions: INO can be confirmed and characterised by level of severity using Z score analysis of quantitative oculography. Such assessments may be useful for linking the level of severity of a specific clinical disability with neuroradiological measures of brain tissue pathology in multiple sclerosis.

Mechanism of Urinary Calcium Regulation by Urinary Magnesium and pH

Urinary magnesium and pH are known to modulate urinary calcium excretion, but the mechanisms underlying these relationships are unknown. In this study, the data from 17 clinical trials in which urinary magnesium and pH were pharmacologically manipulated were analyzed, and it was found that the change in urinary calcium excretion is directly proportional to the change in magnesium excretion and inversely proportional to the change in urine pH; a regression equation was generated to relate these variables (R(2) = 0.58). For further exploration of these relationships, intravenous calcium chloride, magnesium chloride, or vehicle was administered to rats. Magnesium infusion significantly increased urinary calcium excretion (normalized to urinary creatinine), but calcium infusion did not affect magnesium excretion. Parathyroidectomy did not prevent this magnesium-induced hypercalciuria. The effect of magnesium loading on calciuria was still observed after treatment with furosemide, which disrupts calcium and magnesium absorption in the thick ascending limb, suggesting that the effect may be mediated by the distal nephron. The calcium channel TRPV5, normally present in the distal tubule, was expressed in Xenopus oocytes. Calcium uptake by TRPV5 was directly inhibited by magnesium and low pH. In summary, these data are compatible with the hypothesis that urinary magnesium directly inhibits renal calcium absorption, which can be negated by high luminal pH, and that this regulation likely takes place in the distal tubule.

Myeloperoxidase promotor polymorphism and risk of hepatoblastoma

Myeloperoxidase (MPO) is a major enzyme found in neutrophils. Oxidation by MPO produces free radicals that demonstrate genotoxic properties. A polymorphism (G to A) within the promotor region of the MPO gene reduces transcription and expression. This polymorphism is associated with a protective effect against some cancers in adults including lung cancer. The objective of our study was to investigate the effect of this MPO polymorphism on the risk of hepatoblastoma, the most common cancer of the liver in childhood. By using PCR‐SSCP, we determined the genotype at this polymorphism in 48 cases of Caucasian children with hepatoblastoma and 180 normal controls. Genotypes were confirmed by a second method using Aci I restriction enzyme restriction. We found that A allele was associated with reduced risk of hepatoblastoma of 50% (OR, 0.51; 95%CI, 0.27–0.93) and G/A or A/A genotype reduced the risk by 56% (OR, 0.44; 95%CI, 0.21–0.90). Our data suggest that A allele is a protective factor with regard to the risk of hepatoblastoma, perhaps by altering genotoxic properties of xenobiotic substances which may act as carcinogens.

Posttraumatic stress symptoms in children recovering from minor orthopaedic injury and treatment

Background: This study was designed to determine the prevalence of high levels of posttraumatic stress disorder (PTSD) symptoms among pediatric orthopaedic trauma patients recovering from injury and to see whether injury or demographic variables are associated with the presence of the symptoms. Methods: Four hundred pediatric orthopaedic trauma patients completed the Child PTSD Symptom Scale questionnaire. Demographic and injury variables were tested to see if any were associated with the presence of high levels of posttraumatic stress symptoms. Results: The average age of respondents was 11 years. The average time since injury was 36 days. The mean Injury Severity Score and summed Extremity Abbreviated Injury Score were 4 and 2, respectively. A total of 130 (33%) met criteria for high levels of PTSD symptoms. None of the variables tested were associated with high levels of PTSD symptoms, except one. Patients admitted to the hospital after injury were significantly more likely to develop high levels of PTSD symptoms. Conclusions: High levels of posttraumatic stress disorder symptoms are common in the recovery period after pediatric orthopaedic trauma, even among patients with relatively minor injury. Children admitted to the hospital after injury are at higher risk for such symptoms.

Neonatal pneumonia: comparison of 4 vs 7 days of antibiotic therapy in term and near-term infants.

OBJECTIVE: To compare a 4-day course of antibiotic therapy to a 7-day course in selected term and near-term neonates with pneumonia.METHODS: The diagnosis of pneumonia was made in neonates admitted to the normal Newborn Nursery (NBN) who later had signs of respiratory distress and whose chest radiographs were consistent with pneumonia. Infants were excluded if any of the following was present: moderate or thick meconium-stained amniotic fluid, prior antibiotic therapy >24 hours, or need for supplemental oxygen >8 hours. Infants who were asymptomatic after 48 hours of antibiotic therapy were prospectively randomized to a 4-day group (n=35) or a 7-day group (n=38). Infants in the 4-day group were observed in the hospital for 24 hours following cessation of antibiotics and were seen in follow up within several days of discharge.RESULTS: The groups were comparable with regard to demographic factors, duration of rupture of membranes, and incidence of maternal chorioamnionitis. Median postnatal age at the time of identification of respiratory distress symptomatology was 19 hours (range 0.5 to 55 hours) in the 4-day group and 12 hours (range 1 to 72 hours) in the 7-day group. No study infants had a positive blood culture. Mean reduction in length of hospitalization was 2.1 days, with estimated savings of greater than US

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700 per shortened hospitalization. Two infants in the 4-day group developed tachypnea during the 24-hour observation period. However, no infants were rehospitalized for sepsis or pneumonia following discharge. With 95% confidence, the true rate of success for the 4-day group was at least 92%.CONCLUSION: Four days of antibiotic therapy plus a 24-hour period of observation for selected cases of neonatal pneumonia appears to be comparable to 7 days of therapy. It is important to note that newborns in our institution receive a single dose of penicillin soon after birth as part of our group B streptococcal sepsis prophylaxis program, and all infants in this study received prophylaxis prior to the onset of respiratory symptoms. Furthermore, only infants who were asymptomatic after 48 hours of antibiotic therapy were included in this study, and a 24-hour observation period at the end of the 4-day course was required. These qualifications should be taken into account before use of this approach is considered, and additional studies are necessary to further establish its safety and benefits.