Antibiotic failure in a renal transplant patient with Rhodococcus equi infection: an indication for surgical lobectomy.

Rhodococcus equi is an animal pathogen that causes infrequent but challenging infections in immunocompromised individuals, few of which have been described in solid organ transplant recipients. Common clinical presentations include indolent cough, fever, and dyspnea, with necrotizing pneumonia and cavitation. We report a case of a dense right upper lung pneumonia with resultant R. equi bacteremia in a renal transplant recipient. Our patient initially responded to antibiotic treatment with resolution of bacteremia and clinical recovery, followed by interval progression in her right upper lobe consolidation on follow-up computed tomography scans. She underwent lobectomy for definitive therapy with resolution of symptoms. Lobectomy can be utilized in isolated infection after antibiotic failure with excellent clinical outcomes.

Relationship of Multiplex Molecular Pneumonia Panel Results With Hospital Outcomes and Clinical Variables.

BACKGROUND: Antibiotic treatment decisions in severely ill patients must often be made in the absence of microbiologic results. The recently Food and Drug Administration-cleared BioFire FilmArray Pneumonia Panel (PN) detects 15 bacteria semiquantitatively, 3 atypical pneumonia bacteria, 8 viruses, and 7 antimicrobial resistance markers by multiplex PCR in ~1 hour in the laboratory. Previous reports have shown that the PN Panel bacterial detections are highly accurate, even when routine culture had no growth. METHODS: Consecutive bronchoalveolar lavage and endotracheal specimens submitted for culture between June and September 2018 from 270 patients with sufficient clinical and laboratory data were tested with the PN Panel. Patients were divided into 3 groups: (1) both culture and PN Panel positive, (2) PN Panel positive but culture uninformative (no growth or normal flora), and (3) patients with no PN Panel detections. RESULTS: Groups 1 and 2 had significantly higher maximum temperatures on the day of culture (P = .00036, analysis of variance [ANOVA] with Bonferroni correction), higher levels of an inflammatory response as measured by percent polymorphonuclear leukocytes in bronchoalveolar lavage (P = .00025, ANOVA with Bonferroni correction), and gram stain report of white blood cells, as previously reported [1]. CONCLUSIONS: Both group 1 (culture and PN Panel positive), and group 2 (PN Panel positive but culture uninformative) had higher levels of host response inflammatory responses compared with group 3, which had no targets detected, suggesting that PN Panel detections need to be interpreted in the clinical context, even if cultures are discordant. Depending on laboratory turnaround time, there could be opportunities for improved diagnosis and antibiotic stewardship.

Constitutional haploinsufficiency of tumor suppressor genes in mentally retarded patients with microdeletions in 17p13.1.

Chromosome microdeletions or duplications are detected in 10-20% of patients with mental impairment and normal karyotypes. A few cases have been reported of mental impairment with microdeletions comprising tumor suppressor genes. By array-CGH we detected 4 mentally impaired individuals carrying de novo microdeletions sharing an overlapping segment of approximately 180 kb in 17p13.1. This segment encompasses 18 genes, including 3 involved in cancer, namely KCTD11/REN, DLG4/PSD95, and GPS2. Furthermore, in 2 of the patients, the deletions also included TP53, the most frequently inactivated gene in human cancers. The 3 tumor suppressor genes KCTD11, DLG4, and GPS2, in addition to the GABARAP gene, have a known or suspected function in neuronal development and are candidates for causing mental impairment in our patients. Among our 4 patients with deletions in 17p13.1, 3 were part of a Brazilian cohort of 300 mentally retarded individuals, suggesting that this segment may be particularly prone to rearrangements and appears to be an important cause (approximately 1%) of mental retardation. Further, the constitutive deletion of tumor suppressor genes in these patients, particularly TP53, probably confers a significantly increased lifetime risk for cancer and warrants careful oncological surveillance of these patients. Constitutional chromosome deletions containing tumor suppressor genes in patients with mental impairment or congenital abnormalities may represent an important mechanism linking abnormal phenotypes with increased risks of cancer.

Relationship of urinary polyamines to tumor activity and tumor volume in patients.

Serially obtained urinary polyamine levels were determined for 192 patients during a specified time period. The number of patient urine samples totaled 938. The patients had tumors of either the breast, stomach, prostate, or female genital tract, or metastatic carcinomas of unknown origin. Tumor activity and tumor volume, along with other clinical information, were also recorded during the time period. Possible associations between tumor activity and tumor volume on one hand, and polyamine levels on the other hand, were explored via different statistical analyses. For each tumor type, statistically significant group differences were found in polyamine levels between patients with nonactive tumors and patients with active large tumors. Predictive values of polyamine assays for change in disease activity and stability in disease nonactivity for tumors of the breast, female genital tract, and prostate were also computed. For breast tumors, these predictive values do not support the clinical utility of the use of polyamine levels to monitor disease states. For tumors of the female genital tract and prostate, these predictive values yield an indeterminant conclusion.

Further evidence for the use of polyamines as biochemical markers for malignant tumors.

One hundred ninety patients with a variety of tumor presented within a specified time period and fit a specified protocol. Multiple serial urinary putrescine, spermidine, and spermine levels were obtained in these patients, and their disease activity over time, defined as either active or nonactive, was determined by clinical examination, the results of laboratory tests, and radiological criteria. Twenty-four-hr urine collections were used for analysis of polyamine levels. A linear mixed-effects model and the method of maximum likelihood estimation were used for statistical analysis. Statistically significant differences were found in polyamine levels between patients with active or nonactive disease for tumors of the breast, stomach, prostate, female genital tract, and a variety of metastatic carcinomas of unknown origin. There were 105 patients with these tumors; 319 polyamine determinations were obtained from this subset of patients. Our results suggest that serial determination of polyamine levels in urine may have clinical utility for monitoring the disease states for these tumors.

[Digoxin-related leukocytoclastic vasculitis in a very elderly woman: A case report]. / Vascularite leucocytoclasique liée à la digoxine chez une femme très âgée : à propos d'un cas.

Even though digoxin causes many side effects, few cases of skin involvement are recorded in the French Pharmacovigilance Database. We report a case of leukocytoclastic vasculitis (LV) very probably due to digoxin. A 91-year-old woman, hospitalized following a fall, presented cardiac decompensation in a context of rapid atrial fibrillation requiring treatment with digoxin. Eight days later, a rash appeared on her back and trunk. It was neither itchy, nor painful and persisted despite local treatment. There were no other clinical anomalies. After a few days, the rash spread with appearance of bullous lesions, ulcerations and a necrosis on lymphedema of the two legs. Among the complementary examinations, skin biopsy revealed LV with necrosis and subepidermal detachment suggested toxic dermal necrolysis, while direct immunofluorescence was negative. The rash resolved progressively once the digoxin was stopped. The pharmacovigilance department recorded that digoxin was the probable cause. The evidence allowed us to conclude that digoxin was the cause.

Study designs for dose-ranging.

Premarketing dose-ranging studies of a drug are done to establish a reasonable initial dose. According to the current procedure sanctioned by the Food and Drug Administration, each patient is given one of several possible doses, including placebo, after an initial placebo run-in period. Data analysis is based on a model in which the mean response at each dose is independent of the magnitude of the dose. The initial dose is the lowest dose tested that has a response that is statistically significantly greater than the response after placebo administration. We suggest that the present conceptual approach to, and standard study design and analysis for, dose-ranging studies be changed. We believe one must begin with a parametric model for patient-specific dose-response curves. Knowledge of the distribution of these curves in a population provides a basis for choice of an initial dose (e.g., the dose that achieves a given response in a given fraction of patients) and, after observation of response to an initial dose, for choice of an incremental dose for a specific patient (by use of Bayes rule). The current parallel-dose design can provide only poor information about the distribution of dose-response curves, biased estimates of the typical curve, and little information on interpatient variability. Crossover studies provide better information. In studies in which a parametric patient-specific dose-response model is used, a dose-escalation design provides no less information than a crossover design, and it has ethical advantages that allow a more representative patient group and clinical setting to be studied.

Forecasting individual pharmacokinetics.

Often drug dosage may be chosen rationally by use of plasma concentration (CP) as the "therapeutic" end point. The ability to accurately forecast the CP resulting from a dosage regimen is central to choosing that regimen. Tradionally forecasting has been attempted only by accounting for known influences on pharmacokinetics, such as sex, age, and renal disease. One must also adjust for previously observed CPs. Herein, we discuss and explain an approach to both of these tasks, mainly focusing on the latter. The approach balances observed outcomes against prior expectations taking account of observation CP error. For digoxin, use of 1 measured CP, as opposed to none, improves forecast precision for future CPs by 40% (decrement in variance of forecast error), and 2 CPs improve it by 67%. There is also an increase in forecast accuracy (decrement in mean of forecast error) as the number of CPs used increases. After only 2, forecast accuracy and precision are as good as theoretically possible. Moreover, information from CPs is far more valuable for forecasting than that from observable patient features-sex, age, and the like; use of all the latter information does not improve accuracy and precision as much as only 1 CP.

Sudden infant death syndrome in twins.

The incidence of sudden infant death syndrome is higher among twins than it is among singleton infants. Incidence of sudden infant death syndrome in twins in South Australia, is discussed, as well as some features of these twins and the health of the cotwins. The literature concerning the status of the cotwin is reviewed.

Blunt diaphragm rupture. A morbid injury.

A review of our past year's trauma experience revealed that we admitted an average of three patients per month with blunt diaphragm rupture, a total of 39 ruptures in 37 patients. Twenty patients (54%) presented to the emergency room in shock. Thirty patients (81%) required urgent airway intervention. All but one patient had associated injuries. Diaphragm rupture is difficult to diagnose; it was not initially recognized in 69% of cases. Chest roentgenogram was often nondiagnostic. Peritoneal lavage gave false-negative results. We ultimately failed to diagnose diaphragm rupture in only three cases. We attributed our low incidence of missed injury to an aggressive approach in the severely injured patient population, where exploratory laparotomy is a routine part of the complete evaluation. One third of the ruptures were on the right side. The complication rate was 82%, excluding a mortality rate of 40.5%. High morbidity and mortality were related primarily to associated injuries.

The risk of splenorrhaphy.

The main reason for splenorrhaphy is to prevent the occurrence of overwhelming postsplenectomy sepsis. This fear of postsplenectomy sepsis has led to an enthusiasm for splenic salvage to the extent that it may be felt that the injured spleen must be saved at all costs. However, if that is valid, the complications that result from splenic salvage must not exceed the risk incurred by loss of this organ. To assess this, 119 splenic injuries treated by splenorrhaphy were reviewed. These were major splenic injuries that were actively hemorrhaging at laparotomy and, therefore, required specific operative intervention for hemostasis. There were 14 complications in 11 patients (11.8%) directly attributed to the splenorrhaphy. In one patient, the repaired spleen rebled 17 days postoperatively, necessitating splenectomy. Ten patients had persistent or recurrent bleeding, requiring blood transfusions. Three of these underwent reexploration for additional hemostasis. Blood transfusion in association with splenorrhaphy has not previously been considered a complication. However, the literature clearly documents that the risk of blood transfusion heavily outweighs the risk of postsplenectomy sepsis. Therefore, if blood transfusion becomes a necessary adjunct for successful splenorrhaphy, then splenectomy without transfusion is the safer treatment.

Estimating population kinetics.

This paper will review the methods that have been advanced for the estimation of parameters of models quantifying the population characteristics of the kinetic behavior of endogenous and exogenous substances in individuals of the population. Such methods are used frequently, for example, in pharmacokinetic studies. In certain populations, especially biological ones, considerable kinetic variability between population members is present. The models with which we are concerned describe this variability. Some interindividual kinetic variability may be explainable on the basis of measureable concomitant variables, but much of it may remain unexplainable on such a basis. We give this matter particular attention. The assumptions underlying the models are critically discussed.

Successful atrial caval shunting in the management of retrohepatic venous injuries.

Over a 3-year period, 519 patients underwent laparotomy for liver injuries. Nine (2 percent) required insertion of an atrial caval catheter to control hemorrhage from perihepatic venous injuries. In three cases, the shunt arrested the hemorrhage, allowing successful surgical repair of the venous injuries. From a careful analysis of our experience, we have identified common errors made in shunt placement, developed a modified atrial caval catheter, and have simplified the surgical technique for insertion.

Long-term disability associated with flail chest injury.

Twenty-two trauma victims who had sustained flail chest as their only significant injury were evaluated to determine the final outcome. Fourteen patients (63.9 percent) were found to have long-term sequelae. The most common long-term problems after flail chest injury were persistent chest wall pain, chest wall deformity, and dyspnea on exertion. Five patients (22 percent) remained disabled in varying degrees.

Bayesian individualization of pharmacokinetics: simple implementation and comparison with non-Bayesian methods.

One may attempt to individualize drug dosage by estimating an individual's pharmacokinetic parameters. Information useful for this purpose consists of certain population pharmacokinetic parameters (notably those describing the typical relationship between dosage and drug concentrations) and also measured drug concentrations from the individual of concern. Both types of information should be used. A (Bayesian) method that does so has been described in the pharmacokinetic literature. In this report an implementation of the Bayesian method that is readily adapted to a microcomputer is presented. Using simulated data it is compared with two other methods proposed by others, for estimating individual theophylline clearances. Both previously suggested methods are shown to be less precise than the Bayesian method: their typical error magnitudes are 20-70% larger.

Siblings of sudden infant death syndrome victims.

The overall low recurrence rate of SIDS (< 2%) and the lack of concordance in twins are against SIDS being a genetic disorder. The most likely explanations for an increased incidence in siblings are that SIDS constitutes a mixed group of disorders that includes some genetic diseases and some disorders that are known to be recurrent but not genetic, and that some recurrences occur in families in whose lives there is severe deprivation, with many risk factors for SIDS, and in other families whose infant care practices, while not being overtly wrong, increase the risk of SIDS. With improving identification and management of these disorders and risk factors, it is expected that the incidence of SIDS, and, particularly, recurrent incidence in a family, will decrease. The best advice that can be given to families who have had an infant die from SIDS is that for most families the risk of another death from SIDS is very low (< 1%) and that if SIDS does recur, there will not be a prolonged period of suffering for the child. With this information and the recognition by most families that they do not regret having had the child who died, most families are prepared to welcome another pregnancy.

Mesh-sided cots--yet another potentially dangerous infant sleeping environment.

Two cases of accidental asphyxia involving an 11.5 month old boy and a 3.5 month old boy who each died after being trapped between the elastic mesh side of their cots and the cot mattress are reported. In both cases the original cot mattress has either been replaced or augmented by a less well fitting, thicker mattress. Particular problems that exist with these type of mesh sided cots are the potential for considerable stretching of the side of the cot admitting the relatively larger, poorly supported infant head, with elastic recoil of the mesh holding the head in potentially dangerous positions. To help determine whether accidental asphyxia has occurred, death scene examination in cases of sudden infant death during sleep should include reconstruction of the position of the body in the cot or bed, with careful examination of the structure of the cot/bed.

The COMPLY computer program for demonstrating compliance with national radionuclide air emission standards.

The Environmental Protection Agency (EPA) has proposed national radionuclide air emission standards for a number of source categories. One of these standards applies to Nuclear Regulatory Commission Licensees and non-Department of Energy facilities having the potential to release radionuclides to the atmosphere. Approximately 6000 facilities are subject to the standard, which limits the effective whole-body dose commitment to the maximally exposed individual from radionuclide releases to the atmosphere. A computer program to assist the regulated community in determining compliance has been developed by the EPA's Office of Radiation Programs. The computer program COMPLY calculates the dose to an individual residing outside the facility. The program considers dose from inhalation, ingestion of contaminated food, air immersion, and ground deposition. It is based on models developed by the National Council on Radiation Protection and Measurements (NCRP). Compliance procedures provided in COMPLY are designed to reduce the burden on the regulated community. The approach begins with simple-to-use methods that are very conservative in determining compliance. The methods become progressively less conservative but more complicated at succeeding levels. Each higher level requires the input of site-specific information, but allows a more realistic estimate of dose. This paper describes the COMPLY program, and provides estimates of the work required and the degree of conservatism in the dose computed at each level.

Sudden infant death syndrome.

The death of an infant has always resulted in grief and distress to the family involved. When this death occurs in an apparently healthy infant without warning and for no apparent reason, the grief can be magnified and complicated by feelings of confusion, self-recrimination, guilt and fear. Some of these complications can be avoided by early and adequate explanation, and the assurance that while the specific cause of Sudden Infant Death Syndrome is not known, a great deal is known about the condition and this information is available to parents.