Integrating central nervous system metagenomics and host response for diagnosis of tuberculosis meningitis and its mimics.

The epidemiology of infectious causes of meningitis in sub-Saharan Africa is not well understood, and a common cause of meningitis in this region, Mycobacterium tuberculosis (TB), is notoriously hard to diagnose. Here we show that integrating cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) with a host gene expression-based machine learning classifier (MLC) enhances diagnostic accuracy for TB meningitis (TBM) and its mimics. 368 HIV-infected Ugandan adults with subacute meningitis were prospectively enrolled. Total RNA and DNA CSF mNGS libraries were sequenced to identify meningitis pathogens. In parallel, a CSF host transcriptomic MLC to distinguish between TBM and other infections was trained and then evaluated in a blinded fashion on an independent dataset. mNGS identifies an array of infectious TBM mimics (and co-infections), including emerging, treatable, and vaccine-preventable pathogens including Wesselsbron virus, Toxoplasma gondii, Streptococcus pneumoniae, Nocardia brasiliensis, measles virus and cytomegalovirus. By leveraging the specificity of mNGS and the sensitivity of an MLC created from CSF host transcriptomes, the combined assay has high sensitivity (88.9%) and specificity (86.7%) for the detection of TBM and its many mimics. Furthermore, we achieve comparable combined assay performance at sequencing depths more amenable to performing diagnostic mNGS in low resource settings.

Comparison of < 100 cc prostates and > 100 cc prostates undergoing aquablation for benign prostatic hyperplasia.

INTRODUCTION: Surgical options for benign prostatic hyperplasia (BPH) become limited when treating large prostates due to steep learning curves and less effective treatment. Aquablation (AquaBeam System, PROCEPT BioRobotics, Inc., USA) could remedy this. We compare the effectiveness of Aquablation in large prostates between 80 cc and 100 cc and very large prostates > 100 cc. METHODS: WATER II (NCT03123250) is a prospective, multicenter, international clinical trial of Aquablation for the surgical treatment of LUTS/BPH in men of age 45-80 years with prostates between 80 cc and 150 cc. Aquablation was performed using the AquaBeam System. The reported analysis compares the subgroup of patients with a baseline prostate size of < 100 cc versus those with a prostate size of > 100 cc. Students' t test was used for continuous variables and Fisher's test for ordinal/binary variables. RESULTS: Of 114 screened patients, 101 meeting eligibility criteria were enrolled at 13 US and 3 Canadian sites between September and December 2017. Mean operative time was 31.2 ± 8 min in the < 100 cc subgroup and 41.7 ± 14.9 min in the > 100 cc subgroup. The average length of stay following the procedure for the < 100 cc subgroup was 1.5 ± 0.7 days versus 1.7 ± 1.1 days for the > 100 cc subgroup. Mean changes in International Prostate Symptom Score (IPSS), IPSS quality of life, and IPSS voiding and storage subscores were substantial, occurring soon after treatment and averaging (at 3 months) 16.5, 2.8, 10.6, and 5.8 points, respectively (all p < 0.0001). CONCLUSION: Aquablation clinically normalizes outcomes between patients of the < 100 cc and > 100 cc prostate cohorts. It is safe and effective in patients with large prostate glands (> 100 cc) with a smoother learning curve.

Impact of annual surgical volume on length of stay in patients undergoing minimally invasive prostatectomy: a population-based study.

BACKGROUND: On average, patients remain hospitalized no more than 2 days after MIRP. The aim of our study was to examine the temporal trends in length of stay ≥ 3 days and to test the relationship between annual surgical volume (ASV) and annual hospital volume (AHV) and length of stay ≥ 3 days in patients undergoing MIRP. MATERIAL AND METHODS: Within the Florida Hospital Inpatient Datafile, 2439 men who were treated with MIRP for prostate cancer between 2005 and 2008 were identified. Temporal trends were assessed and uni and multi-variable logistic regression models tested the relationship between ASV, AHV and length of stay ≥ 3 days. RESULTS: The average length of stay decreased from 2.4 in 2005 to 1.7 days in 2008. Length of stay ≥ 3 days was recorded in 13.6% of patients and the proportion of patients staying more than ≥ 3 days decreased over time (25.5-12.2%; Chi Square trend p < 0.001). After stratification into low (<1-15 MIRPs) vs. intermediate (16-63 MIRPs) vs. high ASV tertiles (≥ 64 MIRPs) the proportion of patients with length of stay ≥ 3 days were 29.1; 13.2 and 11.1%. In multivariable logistic regression models predicting length of stay ≥ 3 days, ASV, year of surgery and comorbidities achieved independent predictor status and MIRP patients operated by highest ASV tertile surgeons were 71% (p < 0.001) less likely to be hospitalized for more than 3 days. CONCLUSION: The length of stay after MIRP decreased between 2005 and 2008. Surgical expertise represented one of the main determinants of shorter length of stay.

The dimensions and symmetry of the seminal vesicles.

The traditional anatomical description of the seminal vesicles is based on autopsy and imaging studies. Trans-peritoneal robotic-assisted laproscopic surgery, with its three-dimensional magnified view and miniature articulated working instruments, provides an opportunity to perform accurate dissections of the seminal vesicles even when extremely long and tortuous. We used specimens obtained by robotic-assisted laparoscopic radical prostatectomy (RLRP) for accurate anatomic assessment of the dimensions of the seminal vesicles. Digital photos of 78 specimens from men (mean age 59 ± 6.1 years) who underwent RLRP were analyzed using the Image Pro Plus software. Seminal vesicle dimensions were correlated with patients' age, weight, height, prostate weight, sexual function profile (SHIM) and symptom severity score of the lower urinary tract symptoms (IPSS). We found that the length of the seminal vesicles is highly variable (range of 8.5-94.6 mm). The average seminal vesicle length was 31 ± 10.3 mm and its average volume 7.1 ± 5.2 ml. The right seminal vesicle was significantly larger than the left in length, width and volume (P < 0.003). The seminal vesicles were found to be highly asymmetric with a mean difference of 17.8% in length and 24.9% in width between the sides. No correlation between seminal vesicle dimensions and any of the parameters tested was found. We concluded that the normal human seminal vesicles are characterized by marked (11-fold) variation in length and are asymmetric in most patients. The right seminal vesicle is significantly larger than the left. Seminal vesicle dimensions cannot be predicted from other morphometric or physiologic parameters.

Fifteen-year follow-up of transplantation of a cadaveric polycystic kidney: a case report.

INTRODUCTION: Kidneys from donors affected by autosomal-dominant polycystic kidney disease (ADPKD) are in general considered unsuitable for transplantation. To the best of our knowledge, only 12 cases of ADPKD transplanted renal units have been reported in the English literature; most have only short-term follow-up. METHODS: We provide a review of these patients and share our experience with an ADPKD patient who received a 21-year-old deceased donor ADPKD-affected renal transplant and has been closely followed for 15 years. Based on the current literature, this report is the longest follow-up of a ADPKD donor transplant. RESULTS: Over the 15-year follow-up period, there have been no complications related to the ADPKD-affected donor kidney, including three kidney transplant biopsies. The graft continues to function well with the serum creatinine currently 1.2 mg/dL. Serial axial imaging has demonstrated that the cystic disease has slowly progressed in the donor renal unit, with the largest cyst having only increasing from 1.2 to 2.9 cm in diameter. Metachronous, bilateral laparoscopic nephrectomies of the native kidneys were performed owing to intractable pain from cystic enlargement. CONCLUSIONS: Normal functioning deceased donor kidneys that show signs of early ADPKD should be considered acceptable for donation in select cases. These organs provide the recipient a safe, reasonable period of graft survival and have not been shown to cause adverse effects.

[Significance of clinically latent bacterial arthritis]. / Die Bedeutung der klinisch latenten bakteriellen Arthritis.

The classical septic bacterial arthritis is a rare event, but can be distinguished by unequivocal signs such as fibrin exudation and neutrophilic masses (pus). For a long time we have been observing an abortive form of bacterial arthritis in biopsies which subsides spontaneously without antibiotic intervention. Only very early during the course can Staphyolcoccus aureus or epidermidis be detected. Despite the brief presence of bacteria, enzymes from the neutrophils can destroy cartilage and bone. The fact that the attending physician had suspected a bacterial infection in only 7% of these patients highlights the diagnostic complexity. We have termed this form clinically latent bacterial arthritis (CLBA). Structural changes in the synovial membrane, e.g. in rheumatoid arthritis or osteoarthritis, predispose for a hematogenous seeding of endogenous staphylococci and trigger clinically unapparent, temporary infections. This clinically latent bacterial superinfection (CLSI) is also self-limiting, but the high degrading potential of the neutrophilic proteases makes CLSI a very probable contributing factor in joint destruction.

Recurrent metastatic vulvar carcinoma treated with cisplatin plus cetuximab.

Recurrent vulvar carcinoma with metastasis has few effective treatment options, which are mainly directed toward palliation of symptoms. A 70-year-old woman was originally treated in 1999 for vulvar squamous cell carcinoma (SCC) with radical vulvectomy and bilateral inguinofemoral groin dissection. She represented in 2005 with a new lesion distinct from the margin of her first disease occurrence. Although treatment of this area included surgical resection and chemoradiation, she recurred 3 months later. Despite radical surgical resection with an anal perineal resection, she presented 2 months later with widely metastatic disease. Epidermal growth factor receptor (EGFR) staining of the tumor cells showed 3+ staining in 100% of the cells. She was treated with palliative radiation therapy (RT) and a cetuximab plus cisplatin chemotherapy protocol. A partial response was obtained for 5 months with palliation of symptoms. Few treatment options exist for recurrent metastatic vulvar carcinoma. The combination of the EGFR antagonist cetuximab with cisplatin has shown modest success in other metastatic SCCs. The partial response experienced in our patient suggests its potential use in women with recurrent or metastatic vulvar carcinoma.

A para-testicular primitive neuroectodermal tumor in an adult: a case report and literature review.

OBJECTIVE: The authors describe the salient clinical, radiologic and histopathologic features of an extremely rare para-testicular primitive neuroectodermal tumor in a 25 year-old man. INTERVENTION: Excisional biopsy of the tumor en bloc was performed. Adjuvant VAdriaC-based chemotherapy (Vincristine, Doxorubicin, and Cyclophosphamide) was given post-operatively. MAIN OUTCOME MEASURES: Histopathologic examination and immunohistochemical studies were performed on formaldehyde-fixed, paraffin-embedded tumor tissue. RESULTS: Histologic examination showed an undifferentiated small cell tumor. The tumor cells stained positively with MIC-2, a marker specific for primitive neuroectodermal tumors. The patient is 12 months post surgery and has completed adjuvant chemotherapy with no evidence of recurrent disease. CONCLUSIONS: This highly unusual, peripheral primitive neuroectodermal tumor should be considered in the differential diagnosis of undifferentiated small cell neoplasms of the genitourinary system in adults, from the kidney to the testicle. We present a patient with a PNET treated based on a Ewing's family of tumors protocol.

Conducting a workshop.

Conducting a successful workshop is a rewarding accomplishment. To be successful, organization and planning are key factors. Important steps are started early and performed systematically. This article outlines the steps for a successful workshop.

Delayed local treatment of rabbit tibial fractures with biodegradable cefazolin microspheres.

The prevention of infection is a primary objective in the treatment of open fractures. The objective of this study was to compare the efficacy of biodegradable, poly (DL-lactide-co-glycolide) cefazolin microspheres and free cefazolin powder in Staphylococcus aureus contaminated rabbit tibial fractures when treatment was delayed for 2 hours. Fractures were produced in the tibia of rabbits, inoculated with Staphylococcus aureus, and 2 hours later treated by either direct local application of cefazolin microspheres or an equivalent dose of free cefazolin powder. Control animals did not receive antibiotic therapy. The fractures then were stabilized with a bone plate, and the animals were observed for 8 weeks. Local antibiotic therapy with biodegradable cefazolin microspheres prevented the establishment of infection in all animals, and cultures of the tibiae were sterile in all cases. In contrast, clinical evidence of infection developed in 50% of the rabbits that had been treated with free cefazolin powder and 71% of the control animals. Staphylococcus aureus was recovered from the tibiae of 75% and 100% of these animals, respectively. The results of this study suggest that local antibiotic therapy with biodegradable, controlled release cefazolin microspheres may be useful for the management of open fractures in humans, even when treatment is delayed for several hours after bacterial contamination.

Segmental tibial defects. Comparing conventional and Ilizarov methodologies.

Forty-four consecutive patients with segmental debridement defects of the tibia had limb-salvage surgery. Twenty-one patients (Group I) were managed using methods as described by Ilizarov. Twenty-three patients (Group II) underwent conventional treatment with massive cancellous grafts and tissue transfers. Total wound consolidation and infection arrest took place after the first treatment in 71% of the Ilizarov wounds and 74% of the conventionally treated wounds. The major complication rates were 33% and 60% for Groups I and II respectively. The patient population at highest risk for failure was the compromised host treated conventionally (44%). The cost for retreatment and overall success rate (95%) were the same for both groups. Ilizarov reconstructions averaged nine fewer hours in the operating theater, 23 fewer days in the hospital, five fewer months' disability (17 months versus 22 months), and a savings of nearly $30,000 per application.

Bony reconstruction in the lower extremity.

The reconstructions of large debridement defects of the tibia are difficult and, at times, discouraging. To maximize the potential for limb salvage, a rigorous patient selection algorithm is essential. Each therapeutic option must consider various host factors, anatomic restraints, physician skills, and institutional resources. In this article, the cost effectiveness and morbidity of two distinct methodologies are compared to bring the guidelines for patient selection to perspective.