High-throughput sequencing of cerebrospinal fluid for diagnosis of chronic Propionibacterium acnes meningitis in an allogeneic stem cell transplant recipient.

BACKGROUND: A 40-year-old man with chronic myelogenous leukemia presented multiple times over a period of 3 years with episodes of confusion, wide-based gait and falls because of recurrent hydrocephalus despite repeated therapeutic lumbar punctures. These problems occurred in the context of persistent cerebrospinal fluid (CSF) pleocytosis and leptomeningeal enhancement. Extensive diagnostic workups and therapeutic trials had failed to identify a clinically plausible cause or produce any significant improvement in the CSF and neuroimaging abnormalities. METHODS: We used high-throughput metagenomic shotgun sequencing to identify microbes in 2 CSF samples collected from the patient during his illness. These results were compared to sequence data from 1 CSF sample collected during treatment and 5 control CSF samples from other patients. RESULTS: We found sequences representing 53% and 67% of the Propionibacterium acnes genome in 2 CSF samples collected from the patient during his illness. Directed antimicrobial therapy was administered for 6 weeks with resolution of CSF and neuroimaging abnormalities. Sequencing of a sample obtained during treatment demonstrated that the P. acnes levels were decreased to background levels. After insertion of a ventriculo-peritoneal shunt, the patient returned to baseline status. CONCLUSIONS: High-throughput metagenomic shotgun sequencing revealed P. acnes as the cause of chronic meningitis that had eluded conventional attempts at diagnosis. Treatment directed at this organism resulted in cure of the infection and clinical improvement.

Current practices for treatment of respiratory syncytial virus and other non-influenza respiratory viruses in high-risk patient populations: a survey of institutions in the Midwestern Respiratory Virus Collaborative.

BACKGROUND: The optimal treatment for respiratory syncytial virus (RSV) infection in adult immunocompromised patients is unknown. We assessed the management of RSV and other non-influenza respiratory viruses in Midwestern transplant centers. METHODS: A survey assessing strategies for RSV and other non-influenza respiratory viral infections was sent to 13 centers. RESULTS: Multiplex polymerase chain reaction assay was used for diagnosis in 11/12 centers. Eight of 12 centers used inhaled ribavirin (RBV) in some patient populations. Barriers included cost, safety, lack of evidence, and inconvenience. Six of 12 used intravenous immunoglobulin (IVIG), mostly in combination with RBV. Inhaled RBV was used more than oral, and in the post-stem cell transplant population, patients with lower respiratory tract infection (LRTI), graft-versus-host disease, and more recent transplantation were treated at higher rates. Ten centers had experience with lung transplant patients; all used either oral or inhaled RBV for LRTI, 6/10 treated upper respiratory tract infection (URTI). No center treated non-lung solid organ transplant (SOT) recipients with URTI; 7/11 would use oral or inhaled RBV in the same group with LRTI. Patients with hematologic malignancy without hematopoietic stem cell transplantation were treated with RBV at a similar frequency to non-lung SOT recipients. Three of 12 centers, in severe cases, treated parainfluenza and metapneumovirus, and 1/12 treated coronavirus. CONCLUSIONS: Treatment of RSV in immunocompromised patients varied greatly. While most centers treat LRTI, treatment of URTI was variable. No consensus was found regarding the use of oral versus inhaled RBV, or the use of IVIG. The presence of such heterogeneity demonstrates the need for further studies defining optimal treatment of RSV in immunocompromised hosts.

Rapid emergence of daptomycin resistance in clinical isolates of Corynebacterium striatum a cautionary tale.

The objective of this study was to investigate the observation of daptomycin resistance in Corynebacterium striatum, both in vivo and in vitro. We describe a case of C. striatum bacteremia in a patient with a left ventricular assist device (LVAD); the initial isolate recovered was daptomycin susceptible with a minimum inhibitory concentration (MIC) of 0.125 µg/ml. Two months later, and after daptomycin therapy, the individual became bacteremic with an isolate of C. striatum with a daptomycin MIC of >256 µg/ml. To study the prevalence of daptomycin resistance in C. striatum, clinical isolates of C. striatum were grown in broth culture containing daptomycin to investigate the emergence of resistance to this antimicrobial. Molecular typing was used to evaluate serial isolates from the index patient and the clinical isolates of C. striatum we assayed. In vitro analysis of isolates from the index patient and 7 of 11 additional C. striatum isolates exhibited the emergence of high-level daptomycin resistance, despite initially demonstrating low MICs to this antimicrobial agent. This phenotype was persistent even after serial subculture in the absence of daptomycin. Together, these data demonstrate that caution should be taken when using daptomycin to treat high-inoculum infections and/or infections of indwelling medical devices with C. striatum. To our knowledge, this is the first report characterizing the emergence of daptomycin resistance in C. striatum.

Smoking association with influenza infection in renal transplant recipients.

We identified 22 cases of influenza infection among renal transplant recipients and matched them with 66 controls by influenza season to explore risk factors for influenza infection. Active cigarette smoking was associated with influenza infection in this population (adjusted odds ratio 13.1; 95% confidence interval 2.3-76; P = 0.004).

Neurenteric cyst: an unusual cause of third nerve palsy.

INTRODUCTION: Neurenteric cysts are a rare cause of central nervous system compression. Pediatric intracranial cysts are even less common. CASE STUDY: We describe the presentation, imaging features, surgical management, and postoperative course of a 5-year-old female with congenital third nerve paresis, worsening headaches, and a cyst of the third nerve. We performed an eyebrow incision and keyhole supraorbital craniotomy for exploration and subsequent resection of a neurenteric cyst that was densely involved with the third nerve at its exit from the midbrain. Postoperatively, she had chemical meningitis and complete third nerve palsy. This entity is extremely rare in this location but should be included in the differential. We summarize the current literature on these lesions and recommend biopsy and fenestration as surgical treatment.

Exercise tolerance and alcohol intake. Blood pressure relation.

The relations of systolic and diastolic blood pressures to alcohol intake and exercise tolerance levels in 15,612 men and 3,855 women were investigated. Alcohol intake was assessed by questionnaire and stratified into seven levels for men and six for women according to the ounces of ethanol consumed per week. Exercise tolerance was determined by maximal treadmill exercise testing and was categorized into six age-specific by sex-specific levels. Both systolic and diastolic blood pressure were significantly related to both alcohol intake and exercise tolerance levels in both men and women. These relations, which were positive for alcohol and negative for exercise tolerance, remained after covariance adjustment for age, body mass index, and cigarette smoking. Alcohol intake was not significantly correlated with exercise tolerance. The relation of blood pressure to alcohol was not linear because the blood pressure of moderate consumers of alcohol tended to be slightly lower than that of nondrinkers. Higher blood pressure was found only in drinkers whose ethanol intake exceeded 9.5 ounces (approximately 285 ml or 19 drinks) per week. However, heavy drinkers in high exercise tolerance categories had no higher blood pressure than nondrinkers in low exercise tolerance groups. Exercise tolerance or physiological fitness appears to be important in quantifying the relation between alcohol intake and blood pressure and should be considered in describing this relation.

Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy.

We studied the effects of sleep apnea on neuroendocrine function in a cross-sectional study of 225 consecutive men undergoing sleep studies and in a longitudinal study of 43 men with severe obstructive sleep apnea before and after 3 months of successful treatment with nasal continuous positive airways pressure to eliminate upper airways obstruction. Blood samples were collected at 0600-0630 h on awakening for measurement of plasma insulin-like growth factor I (IGF-I), total and free testosterone, sex hormone-binding globulin (SHBG), LH, FSH, PRL, T4, T4-binding globulin, and cortisol. The plasma hormone levels were analyzed in relation to the severity of sleep apnea, as indicated by the desaturation index (the hourly rate of episodes of arterial oxygen desaturation greater than 4% of the stable baseline) and the mean minimal oxygen saturation during the desaturation episodes. In the cross-sectional study plasma IGF-I, free and total testosterone, and SHBG levels were significantly lower in relation to the severity of sleep apnea, whereas plasma LH, FSH, PRL, T4, T4-binding globulin, and cortisol were not. The decreases in plasma IGF-I and total and free testosterone were independent of the effects of aging and adiposity by covariance analysis. In the longitudinal study plasma IGF-I, total testosterone, and SHBG, but not free testosterone, significantly increased after 3 months of nasal continuous positive airways pressure treatment. We conclude that sleep apnea causes reversible neuroendocrine dysfunction in men, which is manifested by decreased plasma. IGF-I, testosterone, and SHBG levels. This neuroendocrine dysfunction is related to the severity of the sleep apnea, as indicated by the nadir levels of arterial oxygen desaturation and the rate of desaturation episodes. These hormonal measurements may provide biochemical markers for both the severity of sleep apnea and its response to therapeutic intervention. In addition, sleep apnea may be a previously unrecognized confounder of the neuroendocrine correlates of aging.

Effect of alcohol and exercise on postprandial lipemia and triglyceride clearance in men.

Alcohol intake and exercise have both been found to be related to increased plasma levels of high density lipoprotein cholesterol (HDLC). Exercise training results in decreased postprandial lipemia, and clearance rate of infused lipids is related to plasma lipoprotein levels in physically active men. The effect of alcohol intake on plasma triglyceride (TG) clearance has not been studied in relation to the exercise status of subjects. Plasma TG change over 8 h was determined following a liquid fatty meal in 14 male habitual runners (R) and 13 physically inactive men (I) after 3 weeks of alcohol abstinence and 3 weeks of drinking approximately 41 g (1.44 oz) of ethanol per day. Fasting total cholesterol and apolipoprotein A-1 (apo A-1) were not different between groups, but TG was lower and HDLC, HDL2C, and HDL3C were higher in the runners. After abstinence, I had slower TG clearance (P = 0.07) compared with R; with alcohol, TG clearance was unchanged in R, but was significantly retarded in I. With alcohol, both groups had increased HDLC levels, but this mainly was due to an increase in HDL3C in R and HDL2C in I; apo A-1 increased similarly in both groups and fasting TG increased significantly only in I. Alcohol-induced increases in postprandial lipemia and retardation of TG clearance appear to occur in inactive, but not exercise-trained subjects and the effect of alcohol on plasma HDL subfractions may differ between these groups.

Management of the adult, spastic, equinovarus foot deformity.

Management of the persistent, acquired, neurogenic equinovarus foot may be a confounding rehabilitative dilemma. Victims of cerebrovascular accidents and traumatic brain injury commonly develop this neurogenic deformity. The plantarflexed and inverted foot position results from an imbalance of forces about the hindfoot due to exaggerated muscle tone and hyperactive stretch reflexes. Significant functional impairment may ensue if a plantigrade foot position cannot be achieved and maintained. Surgical correction may be necessary if conservative measures fail. Determination of the dynamic and static components contributing to the equinovarus deformity is difficult. Gait analysis and dynamic electromyographic studies are valuable adjuncts for operative planning. The wide-ranging goals of surgery vary from improving transfer and ambulation skills, to assisting wheelchair positioning, to facilitating use of braces and/or shoe wear.

The sural nerve in the foot and ankle: an anatomic study with clinical and surgical implications.

Operative procedures and traumatic injuries of the lateral foot and ankle place the sural nerve and its branches at risk. Anatomic studies quantifying the course of this nerve are sparse. In this study, 17 cadaver specimens were dissected to clarify its course and branching patterns. Despite multiple variations of the nerve and its branches, description of the course of a "typical" nerve trunk was possible. The nerve was found to lie in close proximity to the Achilles tendon at a level of 7 cm above the tip of the lateral malleolus. In the hindfoot, the nerve coursed 14 mm posterior and 14 mm inferior to the malleolus. Distally, it crossed superficial to the peroneus longus and brevis tendons. An anastomotic branch coursing into the sinus tarsi area was observed in 24% of specimens. An understanding of the course and distribution of the sural nerve may lessen the risk of iatrogenic injury.

The deep peroneal nerve in the foot and ankle: an anatomic study.

Injury to the deep peroneal nerve in the foot and ankle may result from trauma, repetitive mechanical irritation, or iatrogenic harm. The nerve is most susceptible to injury along its more distal anatomic course. Dissection of 17 cadaver specimens was undertaken to describe the course of the deep peroneal nerve and quantify its branch patterns. In the distal one third of the leg, the nerve was located superficial to the anterior tibial artery between the tibialis anterior and extensor hallucis longus muscles. Typically, the nerve crossed deep to the extensor hallucis longus tendon to enter the interval between the extensor hallucis longus and extensor digitorum longus at an average distance of 12.5 mm proximal to the ankle. A proximal bifurcation was usually present at an average distance of 12.4 mm distal to the mortise. The lateral terminal branch penetrated the deep surface of the extensor digitorum brevis to provide motor innervation. The medial terminal branch passed over the talonavicular joint capsule, and coursed an average of 2.9 mm lateral to the first tarsometatarsal joint. Within the forefoot, it passed deep to the extensor hallucis brevis tendon, bifurcated in the midmetatarsal region, and then arborized, supplying sensibility to the first toe interspace and the adjacent sides of the first and second toes.

Lyme disease: an orthopedic perspective.

The incidence of Lyme disease is increasing. This spirochetal infection may frequently manifest itself with joint involvement without characteristic dermatologic signs or history of tick bite. Serologic testing remains unreliable. Oral or parenteral antibiotics remain the mainstay of treatment. Chronic arthritis develops in approximately 10% of patients with Stage III disease. Lyme arthritis must be considered in the differential diagnosis of patients with mono- or oligoarticular joint involvement, especially in children and young adults with possible tick exposure. Further advances in antimicrobial therapy and serologic testing are anticipated.

Jones' fractures and related fractures of the proximal fifth metatarsal.

At least three fracture types occur in the proximal fifth metatarsal: the Jones' fracture, the proximal diaphysial stress fracture, and the tuberosity avulsion fracture. Each has distinct characteristics. The diaphysial stress fracture is commonly confused with the Jones' fracture, thereby obscuring vital differences in prognosis and treatment. Anatomical and biomechanical characteristics, as well as vascular studies of the proximal portion of the fifth metatarsal, are discussed in an attempt to better understand their diverse healing potentials. Guidelines for treatment are controversial, and must frequently be individualized. Although surgical intervention for certain proximal fifth metatarsal fracture types may speed recovery time, most fractures heal with immobilization. Treatment of displaced, intra-articular fractures, delayed unions, and nonunions usually requires operative methods.

Fixation strengths of patellar tendon-bone grafts.

Secure fixation of bone-patellar tendon-bone grafts is essential to allow early joint mobilization after anterior cruciate ligament (ACL) reconstruction surgery. This study was designed to evaluate four fixation methods of patellar tendon-bone grafts in cadaveric knees. Fifty-one fresh cadaveric patellar tendon-bone specimens were anchored in tibial or femoral metaphyseal bone tunnels. Group I grafts were fixed with Kurosaka interference screws. In Group II the grafts were initially fixed as in Group I, but the screws were then removed, the bone plugs repositioned, and the grafts resecured with screws. In Group III the grafts were anchored with three no. 2 nonabsorbable sutures tied over a screw and washer, whereas in Group IV no. 5 nonabsorbable sutures were used. Each bone specimen was mounted in the biomechanical testing machine, and a vertical tensile load was applied at a strain rate of 51 cm/min until failure of fixation, bone plug fracture, or tendon disruption occurred. The mean force to failure in Groups I, II, III, and IV were 435.0 N, 458.2 N, 454.2 N, and 415.8 N, respectively. There was no significant difference in the force to failure among the four methods of fixation. However, the modes of failure were diverse. In three specimens the Kurosaka screws diverged from the plugs and failed to achieve fixation. These specimens were excluded and will be discussed separately. Although technique-related difficulties may arise, interference screw fixation of patellar tendon-bone grafts affords strong graft fixation--often stronger than the graft itself. Secondary screw fixation appears to be equal in strength to primary screw fixation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-effectiveness of prevention referrals for high-risk HIV-negatives in San Francisco.

We retrospectively assessed the cost-effectiveness of providing prevention referrals to high-risk seronegatives at HIV test sites in San Francisco. We examined the costs and effects from the perspectives of society and the San Francisco Department of Public Health (SFDPH). Cost categories assessed included referral materials, counsellor training and time required to make referrals, prevention services and the value of client time. Effect data are drawn from a study of 289 high-risk seronegatives and the published literature, and are applied to a city-wide caseload of 6,626 high-risk seronegatives. We estimate that a city-wide programme in San Francisco averts two HIV infections per year and yields net savings to society of $43,765, with a cost to the SFDPH of $20,738 per HIV infection averted. We conclude that providing HIV prevention referrals to high-risk seronegatives receiving antibody testing imposes significant costs, but has attractive cost-effectiveness when applied to a large high-risk population.