Interventions for rapid recognition and treatment of sepsis in the emergency department: a narrative review.

BACKGROUND: Sepsis is a major cause of morbidity and mortality worldwide. Early recognition and treatment of sepsis is associated with improved outcome. The emergency department (ED) is the department where patients with sepsis seek care. However, recognition of sepsis in the ED remains difficult. Different alert and triage systems, screening scores and intervention strategies have been developed to assist clinicians in early recognition of sepsis and to optimize management. OBJECTIVES: This narrative review describes currently applied interventions or interventions we can start using today, such as screening scores, (automated) triage systems, sepsis teams and clinical pathways in sepsis care; and it summarizes evidence for the effect of implementation of these interventions in the ED on patient management and outcomes. SOURCES: A systematic literature search was conducted in PubMed, resulting in 39 eligible studies. CONTENT: The main sepsis interventions in the ED are (automated) triage systems, sepsis teams and clinical pathways, the most integrative being a clinical pathway. Implementation of any of these interventions in sepsis care will generally lead to increased protocol adherence. Presumably increased adherence to sepsis guidelines and bundles will lead to better patient outcomes, but the level of evidence to support this improvement is low, whereas implementation of interventions is often complex and costly. No studies comparing different interventions were identified. Two essential factors for success of interventions in the ED are obtaining the support from all professionals and providing ongoing education. The vulnerability of these interventions lies in the lack of accurate tools to identify sepsis; diagnosing sepsis ultimately still relies on clinical assessments. A lack of specificity or sepsis alerts may lead to alert fatigue and/or overtreatment. IMPLICATIONS: The severity and poor outcome of sepsis as well as the frequency of its presentation in EDs make a structured, protocol-based approach towards these patients essential, preferably as part of a clinical pathway.

Optimizing design of research to evaluate antibiotic stewardship interventions: consensus recommendations of a multinational working group.

BACKGROUND: Antimicrobial stewardship interventions and programmes aim to ensure effective treatment while minimizing antimicrobial-associated harms including resistance. Practice in this vital area is undermined by the poor quality of research addressing both what specific antimicrobial use interventions are effective and how antimicrobial use improvement strategies can be implemented into practice. In 2016 we established a working party to identify the key design features that limit translation of existing research into practice and then to make recommendations for how future studies in this field should be optimally designed. The first part of this work has been published as a systematic review. Here we present the working group's final recommendations. METHODS: An international working group for design of antimicrobial stewardship intervention evaluations was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). The group comprised clinical and academic specialists in antimicrobial stewardship and clinical trial design from six European countries. Group members completed a structured questionnaire to establish the scope of work and key issues to develop ahead of a first face-to-face meeting that (a) identified the need for a comprehensive systematic review of study designs in the literature and (b) prioritized key areas where research design considerations restrict translation of findings into practice. The working group's initial outputs were reviewed by independent advisors and additional expertise was sought in specific clinical areas. At a second face-to-face meeting the working group developed a theoretical framework and specific recommendations to support optimal study design. These were finalized by the working group co-ordinators and agreed by all working group members. RESULTS: We propose a theoretical framework in which consideration of the intervention rationale the intervention setting, intervention features and the intervention aims inform selection and prioritization of outcome measures, whether the research sets out to determine superiority or non-inferiority of the intervention measured by its primary outcome(s), the most appropriate study design (e.g. experimental or quasi- experimental) and the detailed design features. We make 18 specific recommendation in three domains: outcomes, objectives and study design. CONCLUSIONS: Researchers, funders and practitioners will be able to draw on our recommendations to most efficiently evaluate antimicrobial stewardship interventions.

The quality of studies evaluating antimicrobial stewardship interventions: a systematic review.

BACKGROUND: Antimicrobial stewardship aims to optimize antibiotic use and minimize selection of antimicrobial resistance. The methodological quality of published studies in this field is unknown. AIMS: Our objective was to perform a comprehensive systematic review of antimicrobial stewardship research design and identify features which limit validity and translation of research findings into clinical practice. SOURCES: The following online database was searched: PubMed. STUDY ELIGIBILITY CRITERIA: Studies published between January 1950 and January 2017, evaluating any antimicrobial stewardship intervention in the community or hospital setting, without restriction on study design or outcome. CONTENT: We extracted data on pre-specified design quality features and factors that may influence design choices including (1) clinical setting, (2) age group studied, (3) when the study was conducted, (4) geographical region, and (5) financial support received. The initial search yielded 17 382 articles; 1008 were selected for full-text screening, of which 825 were included. Most studies (675/825, 82%) were non-experimental; 104 (15%) used interrupted time series analysis, 41 (6%) used external controls, and 19 (3%) used both. Studies in the community setting fulfilled a median of five out of 10 quality features (IQR 3-7) and 3 (IQR 2-4) in the hospital setting. Community setting studies (25%, 205/825) were significantly more likely to use randomization (OR 5.9; 95% CI 3.8-9.2), external controls (OR 5.6; 95% CI 3.6-8.5), and multiple centres (OR 10.5; 95% CI 7.1-15.7). From all studies, only 48% (398/825) reported clinical and 23% (190/825) reported microbiological outcomes. Quality did not improve over time. IMPLICATIONS: Overall quality of antimicrobial stewardship studies is low and has not improved over time. Most studies do not report clinical and microbiological outcome data. Studies conducted in the community setting were associated with better quality. These limitations should inform the design of future stewardship evaluations so that a robust evidence base can be built to guide clinical practice.

Relevance of healthcare-associated pneumonia for empirical antibiotic therapy in the Netherlands.

BACKGROUND: There is no consensus whether patients with healthcare-associated pneumonia (HCAP) should be considered as a patient with hospital-acquired pneumonia (HAP) and treated with broad-spectrum antibiotics, or as a patient with community-acquired pneumonia (CAP), and treated with narrow-spectrum antibiotics. HCAP research has focused mostly on the predictive value for non-susceptibility to broad-spectrum antibiotics and multi-drug resistant pathogens, in settings with moderate to high levels of antibiotic resistance. We investigated whether HCAP criteria predicts non-susceptibility to different empirical strategies, including narrow-spectrum antibiotics in the Dutch setting. METHODS: In a post hoc analysis of patients with moderate-severe CAP in seven Dutch hospitals, we compared in vitro antibiotic susceptibilities of definite and possible causative pathogens of CAP and HCAP to amoxicillin and broader antibiotic regimens. In a sensitivity analysis, pathogens with missing susceptibilities were assumed susceptible (best-case scenario) or non-susceptible (worst-case scenario). RESULTS: Among 2,283 patients with moderate-severe CAP, 23.1% (n = 527) were classified as HCAP. Non-susceptibility to amoxicillin ranged from 11.3% (95% CI 9.9-12.8%; best-case) to 14.4% (95% CI 12.8-16.1%; worst-case) in CAP patients and from 16.7% (95% CI 13.8-20.1%; best-case) to 19.7% (95% CI 16.6-23.3%; worst-case) in HCAP patients. The largest reduction in non-susceptibility was achieved by adding ciprofloxacin to amoxicillin treatment in both CAP patients (10% absolute risk reduction) and HCAP patients (11-16% reduction). CONCLUSIONS: In the Netherlands, HCAP criteria predict higher amoxicillin non-susceptibility in patients hospitalized with moderate-severe CAP. Although broadening the antibiotic spectrum of empiric treatment reduced the likelihood of non-susceptibility, absolute reductions of non-susceptibility in HCAP patients were too low to justify the universal use of broad-spectrum empirical therapy.No abstract available.

Response Adjusted for Days of Antibiotic Risk (RADAR): evaluation of a novel method to compare strategies to optimize antibiotic use.

OBJECTIVES: The Response Adjusted for Days of Antibiotic Risk (RADAR) statistic was proposed to improve the efficiency of trials comparing antibiotic stewardship strategies to optimize antibiotic use. We studied the behaviour of RADAR in a non-inferiority trial in which a ß-lactam monotherapy strategy (n = 656) was non-inferior to fluoroquinolone monotherapy (n = 888) for patients with moderately severe community-acquired pneumonia. METHODS: Patients were ranked according to clinical outcome, using five or eight categories, and antibiotic use. RADAR was calculated as the probability that the ß-lactam group had a more favourable ranking than the fluoroquinolone group. To investigate the sensitivity of RADAR to detrimental clinical outcome we simulated increasing rates of 90-day mortality in the ß-lactam group and performed the RADAR and non-inferiority analysis. RESULTS: The RADAR of the ß-lactam group compared with the fluoroquinolone group was 60.3% (95% CI 57.9%-62.7%) using five and 58.4% (95% CI 56.0%-60.9%) using eight clinical outcome categories, all in favour of ß-lactam. Sample sizes for RADAR were 38% (250/653) and 89% (580/653) of the non-inferiority sample size calculation, using five or eight clinical outcome categories, respectively. With simulated mortality rates, loss of non-inferiority of the ß-lactam group occurred at a relative risk of 1.125 in the conventional analysis, whereas using RADAR the ß-lactam group lost superiority at a relative risk of mortality of 1.25 and 1.5, with eight and five clinical outcome categories, respectively. CONCLUSIONS: RADAR favoured ß-lactam over fluoroquinolone therapy for community-acquired pneumonia. Although RADAR required fewer patients than conventional non-inferiority analysis, the statistic was less sensitive to detrimental outcomes.

Predictors for individual patient antibiotic treatment effect in hospitalized community-acquired pneumonia patients.

OBJECTIVE: Our objective was to identify clinical predictors of antibiotic treatment effects in hospitalized patients with community-acquired pneumonia (CAP) who were not in the intensive care unit (ICU). METHODS: Post-hoc analysis of three prospective cohorts (from the Netherlands and Spain) of adult patients with CAP admitted to a non-ICU ward having received either ß-lactam monotherapy, ß-lactam + macrolide, or a fluoroquinolone-based therapy as empirical antibiotic treatment. We evaluated candidate clinical predictors of treatment effects in multiple mixed-effects models by including interactions of the predictors with empirical antibiotic choice and using 30-day mortality, ICU admission and length of hospital stay as outcomes. RESULTS: Among 8562 patients, empirical treatment was ß-lactam in 4399 (51.4%), fluoroquinolone in 3373 (39.4%), and ß-lactam + macrolide in 790 (9.2%). Older age (interaction OR 1.67, 95% CI 1.23-2.29, p 0.034) and current smoking (interaction OR 2.36, 95% CI 1.34-4.17, p 0.046) were associated with lower effectiveness of fluoroquinolone on 30-day mortality. Older age was also associated with lower effectiveness of ß-lactam + macrolide on length of hospital stay (interaction effect ratio 1.14, 95% CI 1.06-1.22, p 0.008). CONCLUSIONS: Older age and smoking could influence the response to specific antibiotic regimens. The effect modification of age and smoking should be considered hypothesis generating to be evaluated in future trials.

PHOTOFRIN-mediated photodynamic therapy for treatment of early stage oral cavity and laryngeal malignancies.

BACKGROUND AND OBJECTIVE: To determine the efficacy of PHOTOFRIN-mediated photodynamic therapy (PDT) for treatment of diffuse "field cancerization" of the oral cavity and Cis-T2N0M0 squamous cell carcinoma (SqCCa) of the larynx in patients not amenable or that have failed conventional head and neck treatment. STUDY DESIGN/MATERIALS AND METHODS: Over the past 15 years 10 patients with early stage Tis-T2N0M0 SqCCa of the oral cavity and oropharynx and 10 patients with Tis-T2N0M0 SqCCa of the larynx were treated. Intravenous PHOTOFRIN (porfimer sodium) (dose 2.0 mg/kg) was administered outpatient, followed 48-60 hours later by intraoperative light photoactivation at 630 nm via fiberoptic microlens (ML) delivery (surgical light dose, 50-100 J/cm(2)) and/or cylindrical diffuser (CD) delivery (80-100 J/cm). RESULTS: Complete responses (CRs) (follow up 6 months-9 years) were achieved in eight of 10 patients with diffuse field cancerization of the oral cavity. CRs (follow up 6 months-8 years) were achieved in eight of 10 patients with superficial laryngeal cancer obviating the need for total laryngectomy in previously treated radiation therapy patients. CONCLUSION: PHOTOFRIN-mediated PDT provides a surgical oncologic modality for potentially curative treatment of early stage oral cavity and laryngeal malignancies with minimal side effects, absence of systemic toxicity, preservation of oral function and voice quality, with multiple drug administration, and laser light retreatment capability.

Photofrin-mediated photodynamic therapy for treatment of aggressive head and neck nonmelanomatous skin tumors in elderly patients.

OBJECTIVES/HYPOTHESIS: Aggressive nonmelanomatous skin tumors (basal cell carcinoma, squamous cell carcinoma, and Bowen's disease) of the head and neck often occur in Caucasian elderly patients because of prior history of radiation therapy for teenage acne and adenoid hypertrophy; severe solar-induced skin damage, basal cell nevus syndrome, and other genetic skin diseases; chemical carcinogen exposure; and drug-induced immunosuppression. In patients with large, multifocal recurrent tumors, standard therapy with acceptable cosmetic outcomes may be difficult. Photodynamic therapy (PDT) with photosensitizing agents selectively taken up by skin provides a primary or adjunct intraoperative option for treatment of this special group of cancer patients. STUDY DESIGN: Retrospective review. METHODS: Patients (age range, 60-92 y) were injected with 1.0 mg/kg PHOTOFRIN (dihematoporphyrin derivative) followed 60 hours later by intraoperative laser light activation. Light was delivered through microlens fiber by means of an argon dye laser at 630 nm at a light dose of 100 to 300 J/cm2 microlens delivery for PDT alone and 50 to 100 J/cm2 microlens delivery for tumor bed resection sites in the case of adjunct PDT combined with surgical resection. RESULTS: Twelve cases of aggressive recurrent nonmelanomatous cutaneous tumors of the head and neck were treated. Five patients received intraoperative PDT combined with surgical resection, including radical mastoidectomy, lateral temporal bone resection, partial maxillectomy with temporalis myofacial flap reconstruction, and wide local resection with secondary intention healing of exposed scalp wounds. Seven patients were treated with PDT alone for extensive multiple cutaneous lesions or wide-field primary or recurrent nonmelanomatous tumors. Ten patients achieved complete responses (follow-up, 6-60 mo) with excellent wound healing and cosmetic outcomes. CONCLUSIONS: PHOTOFRIN-mediated PDT is an excellent locoregional oncological modality for aggressive primary or recurrent basal cell carcinoma and squamous cell carcinoma, particularly in elderly patients who were previously treated with extensive Mohs microsurgery, surgical resection, and external-beam radiation therapy. Multiple repeat treatments are well tolerated, painless, without systemic morbidity, and amenable to local anesthesia or intravenous sedation for PDT alone, and wound healing and cosmetic outcomes are excellent.

The prognostic value of PSA levels in radiation therapy of patients with carcinoma of the prostate: the UCLA experience 1988-1992.

BACKGROUND AND OBJECTIVES: Pretreatment prostate-specific antigen (PSA) levels may be of prognostic significance for patients with prostate cancer. Posttreatment PSA data are more limited. This study was undertaken to examine the prognostic role of pretreatment and posttreatment PSA levels in the radiation treatment of patients with carcinoma of the prostate. METHODS: One hundred one patients who received primary radiation therapy at UCLA between 1988 and 1992 for clinical stage A to D1 prostate cancer were analyzed. Included were 4 patients with stage A, 77 with stage B, 16 with stage C, and 4 with stage D. All patients had pretherapy and posttherapy PSA values. Patients received definitive radiation therapy with photons (81), neutrons (13), or interstitial implant (7). Correlations were made with other prognostic factors and treatment outcome. RESULTS: Median follow-up was 28 months. At last follow-up, 64% were without evidence of disease, 17% had rising PSA profiles or failure of PSA to normalize (chemical failure), and 19% had local recurrence and/or distant metastases. The 4-year overall survival was 85%, whereas actuarial survival free of chemical or clinical failure was only 32%. Pretreatment PSA levels and posttreatment PSA level normalization at 6 months correlated significantly with disease-free survival. On univariate analysis, pretreatment PSA levels correlated significantly with stage, high versus low Gleason score, and outcome. Posttreatment PSA level normalization at 6 and 12 months correlated with stage, pretreatment PSA level, and outcome, but not with Gleason score. Only PSA level normalization at 6 months and age were independent variables using multivariate analysis. PSA nadir values differed significantly between patients free of disease and those who failed. CONCLUSIONS: In our analysis, posttreatment PSA levels were independently predictive of outcome, whereas pretreatment PSA levels, while correlating with other prognostic factors, were not independently predictive. Given the prognostic value of posttreatment PSA levels, it is appropriate that chemical failures be included in outcome analyses, although this will lower disease-free survival.

Radiation recall dermatitis and pneumonitis in a patient treated with paclitaxel.

BACKGROUND: Radiation recall refers to a tissue reaction produced by a chemotherapeutic agent in a previously irradiated field that would not occur in a nonirradiated field. A number of agents have been reported to cause radiation recall. Recently, there have been case reports of recall dermatitis from paclitaxel treatment. METHODS: A patient with metastatic lung cancer received palliative radiation to her mediastinum and ribs. Because of disease progression, she subsequently received paclitaxel. RESULTS: After paclitaxel administration, the patient became acutely dyspneic. A subsequent chest X-ray revealed a parenchymal opacity in a region that corresponded with the patient's radiation portal. She also developed a severe skin reaction in the previously treated electron field. CONCLUSIONS: This is one of few reported cases of recall dermatitis from paclitaxel and is also suggestive of recall pneumonitis, a phenomenon previously unreported to the authors' knowledge. Given paclitaxel's ability to function as a radiosensitizer, this response is not unexpected. As the frequency of paclitaxel administration increases, its potential as a radiation sensitizer and radiation recall should be considered.

Ototoxicity of chemotherapeutic agents.

This chapter summarizes the reported ototoxicity data on the most clinically important ototoxic chemotherapeutic agents, notably emphasizing the oto(neuro)toxicities of the more commonly administered platinum compounds, cisplatin and carboplatin. Currently, in the United States, the only other marketed ototoxic chemotherapeutic agents are nitrogen mustard, alpha-difluoromethyl ornithine (DFMO), and the vinca alkaloids (vincristine and vinblastine sulfate); for these groups, animal ototoxicity data is sparse, and audiovestibular records of human ototoxicity are not available from most prospective, randomized controlled clinical trials. Future phase I, II, and III clinical oncologic trials of "experimental" chemotherapeutic agents should include methodology for audiovestibular monitoring, just as present FDA-approved cancer protocols with either monotherapy or combined therapy of known "ototoxic" agents should include standardized audiovestibular assessment in the database. Finally, continued clinical application of cisplatin alone or in combination with other chemotherapeutic agents in the successful treatment of solid tumors mandates decreasing or eliminating specifically the dose-dependent sensorineural hearing loss (partially in cases of complete or long-term partial remission) in addition to other common antiproliferation-induced side effects (nephritis, peripheral neuropathy, intractable nausea and vomiting, electrolyte imbalance, anaphylactic-like reactions, and myelosuppression). Because of the chemotherapeutic superiority of cisplatin, it is essential to continue to investigate methods of altering the dose-limiting oto(neuro)toxicity without causing a "counterproductive" reduction of the antitumor activity of cisplatin (or other second- or third-generation ototoxic platinum agents).

Cisplatin-induced ototoxicity: the effect of pigmentation and inhibitory agents.

Cis-diamminedichloroplatinum II (cisplatin), a divalent platinum compound and potent cell-cycle nonspecific chemotherapeutic agent, produces a dose-limiting, permanent, high-frequency sensori-neural hearing loss and peripheral neuropathy, and a dose-related cumulative renal insufficiency with tubular necrosis and interstitial nephritis. The potential for dose-limiting and permanent cochlear (neuro) toxicity remains despite present methods of hypertonic saline, prehydration, and mannitol diuresis prior to drug administration. The exact mechanism(s) of ototoxicity and/or nephrotoxicity are still unknown. Continued aggressive high-dose cisplatin chemotherapy necessitates the investigation of ways to decrease the dose-limiting side effects that inhibit the administration of cisplatin at therapeutic and tumoricidal doses. This multifaceted project investigates two categories of potential inhibitors of cisplatin toxicity that, when coadministered with a known tumoricidal and ototoxic dose of cisplatin, will decrease or inhibit the ototoxicity: 1. phosphonic acid antibiotics (fosfomycin; 1,2 epoxypropylphosphonic acid); 2. nonglucocorticoid 21-aminosteroids, which are free oxygen radical scavengers (LAZAROIDS: U74006F and U78517F). This project also investigates the role of pigmentation as a variable affecting the evaluation of platinum-induced ototoxicity in the guinea pig animal model. Identification of an optimal animal model for future cisplatin toxicity research should be based on previously established species-specific differences in total drug dose, systemic toxicity, and morphological and functional evidence of cochlear toxicity, as affected by differences in pigmentation and drug tolerance. Cytocochleography, brainstem auditory evoked response (BSER), scanning and transmission electron microscopy of organ of Corti and the stria vascularis, double-blind light microscopy of renal, small intestine, and peripheral nerve tissue, and gamma-emission analysis of 195Mplatinum localization in inner ear neuroepithelium and the stria vascularis are used in the global evaluation of the ototoxic effects of cisplatin in both the adult albino and pigmented guinea pig.

Breast cancer after radiation exposure in childhood.

Reports in the literature link radiation in childhood to some form of breast cancer in later life. The authors present a report on the carcinogenic effects of chemotherapy and radiation on the pubescent breast of a 12-year-old female treated for Wilms' tumor of the left kidney.

The protective effects of allopurinol and superoxide dismutase-polyethylene glycol on ischemic and reperfusion-induced cochlear damage.

The purpose of this study was to assess the protective effects of allopurinol, a blocker of free oxygen radical (FOR) formation, and superoxide dismutase-polyethylene glycol (SOD-PEG), a scavenger of FORs, on ischemic and reperfusion-induced cochlear damage. Fifteen Wistar Kyoto rats (WKY) were randomly assigned to three groups: (1) a control group (5 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion as documented by laser Doppler flowmetry; (2) a drug-treated group (5 animals) that received allopurinol before ischemia/reperfusion; and (3) a drug-treated group (5 animals) that received SOD-PEG before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) of the cochlea was abolished, and the cochlear microphonic (CM) was reduced after ischemia. In contrast, both allopurinol and SOD-PEG-treated animals showed post-reperfusion sensitivity in CAP and CM measures. We interpret these results to indicate that damage to the cochlear from ischemia and subsequent reperfusion can be attenuated by pretreatment with allopurinol or SOD-PEG. This provides indirect evidence that FORs may be partially responsible for cochlear damage resulting from ischemic conditions.

Perilymphatic fistula: analysis of free amino acids in middle ear microaspirates.

High-performance liquid chromatography was used to determine 19 free amino acid concentrations in perilymph, serum/plasma, and red blood cell intracellular fluid. Significant differences were found between perilymph and these fluids. Free amino acid analysis was then used to quantitatively analyze middle ear microaspirates in order to test the hypothesis that perilymph is a potential source of clear fluid in perilymphatic fistulas (PLF). Fourteen unknown samples from patients with visually identified PLF, including patients with no identifiable otic capsule defect, were studied. Six samples on amino acid pattern analysis were correlated most similarly with perilymph (rrho greater than 0.95). Four of these six samples were scored on the basis of quantitative amino acid values as similar to perilymph. However, three samples of clear fluid were more similar to serum/plasma than to perilymph on both amino acid pattern and quantitative amino acid score analysis. These results objectively suggest perilymph as a potential source of clear fluid in some patients with a diagnosis of PLF. Not all clear fluid observed in the middle ear, however, is potentially perilymph.

Cochlear implant flap necrosis: adjunct hyperbaric oxygen therapy for prevention of explantation.

The most common complication resulting from cochlear implant surgery involves the skin flap: scalp breakdown, flap necrosis, and implant exposure requiring explantation. A 5.4 percent flap complication rate has been reported with the C-shaped postauricular flap (anteriorly-based on the superficial temporal and occipital arteries) in contrast to a 0 percent flap complication rate with the Australian inverted U-flap (inferiorly-based on the occipital artery). The literature is scant concerning detailed management of flap necrosis in order to obviate cochlear implant removal. Presented is an illustrative case of full thickness C-shaped flap necrosis with resultant exposure of a Nucleus multichannel implant. Successful wound management required pre- and postoperative hyperbaric oxygen in conjunction with a transposition flap closure of the scalp defect. Cochlear explantation was not necessary and rehabilitation and implant function were excellent 18 months postoperatively.

Free amino acid analysis of guinea pig perilymph: a possible clinical assay for the PLF enigma?

Controversy prevails regarding the accuracy of the clinical diagnosis of perilymphatic fistula (PLF). The diagnosis of PLF has been based on the subjective evaluation of vestibular function tests and the intraoperative macroscopic visualization of "clear fluid" from the oval/round windows at the time of exploratory tympanotomy. However, the subjective visual characterization of PLF varies among observing surgeons. Furthermore, perilymph can be "contaminated" with serum, blood, cerebrospinal fluid (CSF), and local anesthesia. This article presents a scientific biochemical microassay for the free amino acid profile of perilymph. Microaliquots of uncontaminated perilymph were sampled from the bilateral round windows (scala tympani) of 20 guinea pigs and analyzed for 19 free amino acid concentrations (FAAC) by high-performance liquid chromatography (HPLC). These samples were compared with the FAAC of guinea pig serum samples. Perfect predictor value ranges were nonoverlapping for 12 of 19 free amino acids in perilymph vs. plasma. Amino acid microassay of middle ear fluid for verification of "true" perilymph vs. nonperilymph fluids by the identification of nonoverlapping FAA markers may allow scientific verification of the existence of PLF in "suspected" patients.

Hyperbaric oxygen management of chronic staphylococcal osteomyelitis of the temporal bone.

Hyperbaric oxygen (HBO) has proven efficacious in the adjunct management of selected otolaryngologic problems: radiation therapy-induced osteoradionecrosis of the temporal bone, malignant external otitis, mandibular osteoradionecrosis and refractory osteomyelitis, soft tissue head and neck necrotizing fasciitis, compromised skin flaps and grafts, acute air or gas embolism, and otologic barotrauma. Herein is described the management of an insidious Staphylococcus aureus osteomyelitis of the temporal bone by pre- and postoperative HBO in conjunction with surgical debridement. The possible application of angiogenic agents and tetracycline bone-labeling in combination with hyperbaric oxygen therapy in the management of refractory neurotologic disease will be discussed.

Photodynamic therapy for treatment of AIDS-related oral Kaposi's sarcoma.

Since 1975, Phase I and II studies have demonstrated the successfulness of hematoporphyrin derivative photodynamic therapy in the treatment of various malignancies of the skin, eye, bladder, lung, and head and neck. Moreover, two cases of traditional Western cutaneous Kaposi's sarcoma (TKS) have been treated with photodynamic therapy with both early and late complete response. To date, attempts at cure and palliation of the more aggressive AIDS-related oral Kaposi's sarcoma with conventional radiation, chemotherapy or immunotherapy, or surgical excision have been limited and often associated with debilitating mucositis and further immunosuppression. Certain aspects of photodynamic therapy may be efficacious for treatment of Kaposi's sarcoma: (1) the selective retention of hematoporphyrin derivative by neoplastic lesions; (2) a tumor-specific cytotoxic agent (i.e., free oxygen radical); (3) absence of systemic toxicity from immunosuppression; and (4) the potential for retreatment without increasing side effects. Herein we present five cases of AIDS-related KS (EKS) with diffuse, superficial, and nodular oral lesions treated with dihematoporphyrin derivative and photodynamic therapy with subsequent dramatic early partial and complete responses.