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.

Complications following gastrostomy tube insertion in patients with head and neck cancer: a prospective multi-institution study, systematic review and meta-analysis.

OBJECTIVES: To measure morbidity and mortality rates following insertion of gastrostomy tubes in head and neck cancer patients. To determine evidence for any relationship between gastrostomy insertion technique and complication rates. DESIGN: A prospective cohort study and qualitative systematic review. SETTING: Multi-cancer networks in the South West of England, Hampshire and the Isle of White. PARTICIPANTS: One hundred and seventy-two patients with head and neck cancer undergoing gastrostomy tube insertion between 2004 and 2005. Percutaneous endoscopic gastrostomy (PEG) was performed in 121 patients. Fifty-one patients had radiologically inserted gastrostomy (RIG). Twenty-seven studies reporting outcomes following 2353 gastrostomy procedures for head and neck cancer. MAIN OUTCOME MEASURES: Post-procedure mortality, major and minor complications. RESULTS: In the present series, mortality rates were 1.0% (1/121) for PEG and 3.9% (2/51) for RIG. Overall major complication rates following PEG and RIG were 3.3% (4/121) and 15.6% (9/51) respectively. In our systematic review and meta-analysis of 2379 head and neck cancer patients, we observed fatality rates of 2.2% (95% CI 0.014-0.034) following PEG and 1.8% (95% CI 0.010-0.032) following RIG. Furthermore, major complication rates following PEG were 7.4% (95% CI 5.9-9.3%) and 8.9% (95% CI 7.0-11.2%) after RIG. CONCLUSIONS: Procedure related mortality rates following gastrostomy in head and neck cancer patients are higher than those in mixed patient populations. Major complication rates following RIG in head and neck cancer patients are greater than those following PEG. Major complications following PEG in patients with head and neck cancer appear no worse than in mixed pathology groups. We have identified that RIG is associated with increased morbidity and mortality in patients who are ineligible for PEG. The serious nature of the complications associated with gastrostomy particularly in patients with head and neck cancer requires careful consideration by the referring physician.

Synthesis and Stereochemistry of Axinastatin 4

Axinastatin 4 from a marine sponge was synthesized by high-dilution BOP-Cl cyclization of Trp-Val-Pro-Leu-Thr-Pro-Leu in 94% yield (only 2.5% at normal dilution), showing the configurations of the last three amino acids to be S. Synthetic axinastatin 4 was devoid of cytostatic activity.

Risk management of asymmetrical hearing impairment in an armed forces population.

The prevalence of asymmetrical hearing impairment in the entire service population (1490 individuals) of a Royal Air Force flying station was estimated from routine audiometric testing recorded in individuals' medical records. Criteria for magnetic resonance imaging (MRI) scanning to exclude the possibility of vestibular schwannoma were determined in accordance with the risk management principle that the cost of the screening should not exceed the value of the likely benefit. MRI scanning should be carried out in the presence of an asymmetrical sensorineural hearing impairment of (a) 15 dB or more at two adjacent frequencies, or (b) 15 dB or more averaged over 0.5, 1, 2, 3, 4, 6 and 8 kHz.

Application of the Paediatric Throat Disorders Outcome Test (T-14) for tonsillectomy and adenotonsillectomy.

INTRODUCTION: The T-14 questionnaire is a validated patient reported outcome measure (PROM) used to assess the value of paediatric tonsillectomy from the patient's perspective. Tonsillectomy is a procedure under threat. As such, this study aimed to provide further evidence supporting the role of tonsillectomy in the management of recurrent tonsillitis and obstructive sleep apnoea. METHODS: A prospective uncontrolled observational study was undertaken examining 54 paediatric patients undergoing tonsillectomy at our institution. Parents of children having surgery were invited to complete a T-14 questionnaire preoperatively as well as at three and six months postoperatively. RESULTS: The questionnaire was completed for 52 of the 54 patients preoperatively as well as at 3 and 6 months postoperatively (96% response rate). The mean difference between the preoperative and six-month T-14 score was 31.8 (p<0.0001). T-14 scores at three months were also significantly improved compared with those taken preoperatively (mean difference: 29.9, p<0.0001). CONCLUSIONS: This is the first study in the literature to assess T-14 questionnaires at three and six months following paediatric tonsillectomy, providing evidence of the early benefit on PROMs. Tonsillectomy is the most common surgical procedure performed in the UK, and it is regarded highly by patients and otolaryngologists alike. This study provides significant evidence that tonsillectomy improves PROMs, thereby demonstrating its ongoing clinical value as a funded National Health Service procedure.

Rapid treatment of rhinophyma with powered microdebrider.

We describe here our experience in using sinus microdebrider to rapidly debulk and sculpt the tissues in cases of rhinophyma correction. We utilized the use of the 4 mm M4 Rotatable Cutting Straight Sinus Blade on a straight Straightshot M4 Microdebrider by Medtronic at 800 rpm oscillation which is normally utilised in our sinus surgery practice. The microdebrider is straightforward to use and is already stocked in most ENT departments. It requires no additional training or cost outlay for departments that perform endoscopic sinus surgery with microdebrider. In our experience it affords the surgeon the ability to rapidly and accurately sculpt the nose to an excellent aesthetic result. We feel it is a more precise tool than cold steel or Bovie cautery, quicker than CO2 laser techniques, and avoids the aerosol of dermabrasion. No complications occurred in our series, and all patients rated their cosmetic outcome as good to excellent.

Platysma myocutaneous flap for reconstruction of skin defects in the head and neck.

The platysma myocutaneous flap (PMF) is a common reconstructive option for defects in the head and neck region. Its applications have expanded from the reconstruction of intraoral defects to include laryngo-pharyngeal, lip, and cheek defects. The platysma flap can be superiorly, posteriorly, or inferiorly-based. The superiorly-based flap has a robust arterial blood supply but less efficient venous drainage, whereas the opposite is the case with the posteriorly-based flap. We present our results of using a superiorly based PMF flap for reconstruction of defects in the parotid, auricular/mastoid, and cheek regions after resection for squamous cell carcinoma. Of 11 patients, eight had no postoperative complications. The remaining three developed venous congestion of their flaps, in two of whom it led to secondary epidermolysis and limited skin loss. The venous congestion resolved with conservative management, and all flaps remained viable. The PMF flap is an alternative to more complex reconstructive options for skin defects of the auricular, parotid, and cheek regions, and gives a satisfactory cosmetic result.

[Ultrastructural study of the antral mucosa to determine the presence of Helicobacter pylori and its association with chronic active gastritis]. / Estudio ultraestructural de la mucosa antral para determinar Helicobacter pylori y su asociación con gastritis crónica activa.

We present the results of ultrastructural studies of gastric mucosa obtained through upper digestive endoscopy of eight patients with suspicious symptoms of non ulcer dyspepsia or peptic ulcer. Two were male and six female with a median age of 54 years. The urease test to determine the presence of HP and Hematoxylin-Eosin and Warthin-Starry staining techniques were practiced with the purpose of a better detection of bacteria and gastritis. We did not find any correlation between the endoscopic results and the presence of gastritis or HP. Of the 8 patients only one had negative results for HP and for Electron microscopy studies. Chronic active gastritis was seen with light microscopy in all of the cases. Three in this group presented mild focal dysplasia and one case intestinal metaplasia type IIa. The main ultrastructural findings were: a) diminished or absent microvilli underneath the bacteria; b) HP inside phagolysosomes in the cytoplasm of the epithelial cells; c) in some cases, the bacteria was attached to the cell membrane; d) the cellular wall of HP contains mucopolysaccharides and up to four polar flagella; e) there are polymorphonuclear leucocytes in the epithelium. We conclude that Electron Microscopy is not a routine method for studying HP, but it constitutes a good method to study pathogenicity of the bacteria.

An antibacterial vitamin E derivative from Tovomitopsis psychotriifolia.

The crude ethanol extract from the leaves of Tovomitopsis psychotriifolia (Clusiaceae) exhibits antibacterial activity against Bacillus cereus, Staphylococcus aureus, and Pseudomonas aeruginosa. The biologically active agent in the extract has been isolated by chromatographic techniques and identified by NMR spectroscopy as trans-delta-tocotrienoloic acid.

Lupeol is the cytotoxic principle in the leaf extract of Dendropanax cf. querceti.

The crude ethanol extract from the leaves of Dendropanax cf. querceti (Araliaceae) from Monteverde, Costa Rica, exhibits cytotoxic activity against Hep-G2, A-431, and H-4IIE tumor cell lines. The active component has been isolated by activity-directed separation and identified by 1H- and 13C-NMR spectroscopy as the triterpene lupeol. The mechanism of cytotoxic activity of lupeol has been determined to be inhibition of topoisomerase II.

Development of a life events/icon calendar questionnaire to ascertain occupational histories and other characteristics of migrant farmworkers.

BACKGROUND: Specialized methods are necessary to collect data from migrant farmworkers for epidemiologic research. METHODS: We developed a questionnaire that collected lifetime occupational histories and other lifestyle risk factors via a life events/icon calendar, and administered the questionnaire to a convenience sample of 162 migrant farmworkers in nine areas of the U.S. RESULTS: The average duration of the interviews was about 1 h 30 min, with an average of 45 min for the work history section. The occupational histories covered a median of 27.6 years per person for men and 20.8 years per person for women. The median number of years spent in farm jobs was 11.3 for men and 5.8 for women. The median number of farm jobs (crop/task combination) per person was 59 among men and 27 among women. Many farmworkers performed the same crop/task combinations at multiple times throughout their lives, yielding a median of 13 unique farm jobs and 8 unique crops among men and 7 jobs and 5 crops among women. CONCLUSIONS: The project demonstrated that it is feasible to collect detailed work histories and other risk factor data from farmworkers, documented the complexity of work histories encountered among farmworkers, and yielded recommendations for refining a questionnaire that will facilitate future epidemiologic research on farmworkers.