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Biomedical subjects

James S Lewis

Publications and source records attributed to James S Lewis.

At least 19 recordsLinked to original sources

Accuracy of frozen section for HPV-Associated squamous cell carcinoma of unknown primary.

INTRODUCTION: Current guidelines for the management of metastatic squamous cell carcinoma of unknown primary (SCCUP) recommend submission of suspicious primary sites for frozen section analysis (FSA). This study aims to investigate the diagnostic accuracy of FSA for identification of HPV-associated SCCUP. METHODS: A retrospective cohort study of patients with biopsy-proven p16-positive SCCUP who underwent diagnostic operation at two tertiary care institutions was performed. Sensitivity, specificity, PPV, and NPV of diagnostic FSA were assessed. RESULTS: 77 patients were included in analysis. 66 patients underwent definitive TORS (diagnostic TORS operation with subsequent neck dissection after identification of the occult primary tumor), 7 patients underwent diagnostic TORS (TORS to identify occult primary tumor, no neck dissection), and 4 patients underwent direct laryngoscopy and biopsy only. Primary tumors were identified in 63 patients (82%) with a mean tumor size of 1.1 cm. There was no significant difference in size between patients whose tumor was identified on FSA (mean 1.1 cm) and on permanent only (mean 0.9 cm) (p = 0.26). The sensitivity, specificity, PPV, and NPV of FSA for SCCUP was 86%, 100%, 100%, and 86%, respectively. Diagnostic frozen specimens included 52 direct laryngoscopy biopsies and 69 TORS excisions. In the biopsies, sensitivity was 100% and NPV was 100%, whereas in the TORS-excised specimens, sensitivity was 77% and NPV was 77%. CONCLUSIONS: In this case series of 77 patients with SCCUP, the sensitivity and NPV of FSA for identification of the primary tumor was over 85%. FSA is valuable during diagnostic operation for SCCUP.

Humans↗

Community-associated methicillin-resistant Staphylococcus aureus: new bug, old drugs.

OBJECTIVE: To discuss community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections and evaluate older antibiotics as suitable therapeutic treatment options. DATA SOURCES: Searches of MEDLINE, EMBASE, and the Cochrane Library (1966-May 2006) were performed using the key terms methicillin resistance, community-acquired, community associated, treatment, Staphylococcus aureus, mec, and Panton-Valentine leukocidin. STUDY SELECTION AND DATA EXTRACTION: All articles were critically evaluated and all relevant information was included in this review. DATA SYNTHESIS: There has been a documented shift of methicillin resistance occurring in staphylococcal infections manifested within the community. Infections caused by CA-MRSA possess unique characteristics including lack of hospital-associated risk factors, improved susceptibility patterns, distinct genotypes, faster doubling times, and additional toxins. Potential therapeutic options to treat these infections include trimethoprim/sulfamethoxazole (TMP/SMX), clindamycin, tetracyclines, fluoroquinolones, and new antimicrobials. CONCLUSIONS: CA-MRSA infections can be successfully treated with older, oral antibiotic agents including TMP/SMX, clindamycin, and tetracyclines. Fluoroquinolones and linezolid should be avoided as first-line agents.

Anti-Bacterial Agents↗

MRI of the peritoneum: spectrum of abnormalities.

OBJECTIVE: Our objective was to detail peritoneal anatomy, techniques for optimizing peritoneal MRI, and the MRI characteristics of several disease processes that frequently involve the peritoneum. CONCLUSION: Homogeneous fat suppression and dynamic contrast-enhanced imaging, including delayed imaging, are critical technical factors for successful lesion detection and characterization on peritoneal MRI.

Adult↗

Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder-p63, MOC-31, and TTF-1.

Sarcomatoid carcinomas are rare malignancies which represent poorly differentiated epithelial tumors that may be difficult to recognize as such. While some cases may have obvious epithelial areas, the sarcomatoid areas are poorly distinguishable from true sarcoma at the light microscopic level and, by immunohistochemistry, often show only limited staining for traditional epithelial markers such as cytokeratin or epithelial membrane antigen. This can be particularly problematic for diagnosis on small biopsy specimens. We sought to assess the diagnostic utility of several immunohistochemical markers of epithelial differentiation including p63, MOC-31, and thyroid transcription factor-1 on sarcomatoid carcinomas of the head and neck (19 cases; 'spindle cell carcinomas'), lung (19 cases), and urinary bladder (11 cases). These results were compared to immunohistochemistry for the traditional epithelial markers pan-cytokeratin and epithelial membrane antigen. Staining for p63 showed the greatest diagnostic utility, positive in 63, 50, and 36% of head and neck, lung, and urinary bladder sarcomatoid carcinomas, respectively. p63 stains were positive in many cases where immunohistochemistry was negative for both pan-cytokeratin and epithelial membrane antigen. All three alternative markers were quite specific for epithelial differentiation, each staining less than 10% of the control group of 73 various primary and metastatic sarcomas, melanomas, and benign spindle cell lesions. In conclusion, immunostaining beyond traditional pan-cytokeratin and epithelial membrane antigen may have diagnostic utility in this context.

Aged↗

Treatment approaches for community-acquired methicillin-resistant Staphylococcus aureus infections.

PURPOSE OF REVIEW: This review addresses therapeutic approaches to community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections, focusing on recently published data in the English-language medical literature dating from June 2004 to July 2005. RECENT FINDINGS: During the reviewed time period, the overall understanding of the epidemiology and virulence of community-acquired MRSA has continued to advance. This same period has also seen numerous works dealing with the newer and emerging anti-staphylococcal antimicrobial agents. Important clinical trials involving linezolid, daptomycin, tigecycline, dalbavancin, and telavancin have been completed. At the same time, owing to the cost of newer agents and the broad susceptibility pattern of community-acquired MRSA, many older antimicrobial agents (long-acting tetracyclines, fluoroquinolones, rifampin, trimethoprim-sulfamethoxazole, and clindamycin) have also been reexamined. SUMMARY: As data accumulates, the newer antimicrobial agents active against community-acquired MRSA continue to demonstrate their value. Despite the appeal and abundant publications involving newer agents, older antimicrobials certainly retain a therapeutic role. Considerable work needs to be done prospectively evaluating older agents for community-acquired MRSA disease. The most important therapeutic intervention for the majority of community-acquired MRSA infections is adequate drainage of purulent fluid collections. Antimicrobial selection for community-acquired MRSA infections should be governed by disease severity, susceptibility patterns (especially based on timely clinical specimen culture), clinical response to therapy, and cost.

Acetamides↗

Failure of cefepime therapy in treatment of Klebsiella pneumoniae bacteremia.

A case of failure of cefepime treatment of a bloodstream infection with AmpC-producing Klebsiella pneumoniae is reported. The failure was attributed to extended-spectrum beta-lactamase (ESBL) acquisition by the isolate, possibly during therapy. Problems encountered with ESBL detection in AmpC-producing isolates are discussed.

Anti-Bacterial Agents↗

Cost advantage of voriconazole over amphotericin B deoxycholate for primary treatment of invasive aspergillosis.

STUDY OBJECTIVES: Using data from a published clinical trial, our objectives were to compare the cost advantage of voriconazole over amphotericin B deoxycholate (AmBd) for primary treatment of invasive aspergillosis and to determine the financial impact the findings would have in a real-world clinical setting. DESIGN: Pharmacoeconomic analysis. SETTING: University hospital. PATIENTS: Two hundred seventy-seven patients in the modified intent-to-treat population. MEASUREMENTS AND MAIN RESULTS: An analysis was performed of drug acquisition costs for all patients in the modified intent-to-treat population, which consisted of 144 patients in the voriconazole group and 133 in the AmBd group. The analysis included costs of initial drug therapy; conversion from intravenous to oral treatment for patients receiving voriconazole; and the types, dosages, and duration of other licensed [Food and Drug Administration-approved] antifungal therapy (OLAT) for up to three OLAT regimens/patient. Current drug costs for our university hospital were used for all calculations. Total voriconazole costs were $784,405 ($581,008 for initial therapy with voriconazole, $203,397 for OLAT) compared with $852,238 for AmBd ($31,677 for initial AmBd therapy, $820,561 for OLAT). Over the 12-week study period, the cost/patient was $961 less for patients whose initial treatment was voriconazole than for those whose initial treatment was AmBd. Other licensed antifungal therapy accounted for 26% and 96% of total drug costs for voriconazole and AmBd, respectively. Other licensed antifungal therapy was given to 36% of voriconazole-treated patients and 80% of AmBd-treated patients. CONCLUSION: These data demonstrate the importance of evaluating total drug costs when comparing treatment regimens and not just initial therapy. Initial therapy with voriconazole had a cost advantage over AmBd in total antifungal drug cost/patient.

Administration, Oral↗

Inducible clindamycin resistance in Staphylococci: should clinicians and microbiologists be concerned?

The increasing incidence of a variety of infections due to Staphylococcus aureus--and, especially, the expanding role of community-associated methicillin-resistant S. aureus (MRSA)--has led to emphasis on the need for safe and effective agents to treat both systemic and localized staphylococcal infections. Unlike most previously noted strains of health care-associated MRSA, community-acquired MRSA isolates are often susceptible to several non- beta -lactam drug classes, although they are usually not susceptible to macrolides. Several newer antimicrobial agents and a few older agents are available for treatment of systemic staphylococcal infections, but use may be limited by the relatively high cost of these agents or the need for parenteral administration. Inexpensive oral agents for treatment of localized, community-acquired MRSA infection include clindamycin, trimethoprim-sulfamethoxazole, and newer tetracyclines. Clindamycin has been used successfully to treat pneumonia and soft-tissue and musculoskeletal infections due to MRSA in adults and children. However, concern over the possibility of emergence of clindamycin resistance during therapy has discouraged some clinicians from prescribing that agent. Simple laboratory testing (e.g., the erythromycin-clindamycin "D-zone" test) can separate strains that have the genetic potential (i.e., the presence of erm genes) to become resistant during therapy from strains that are fully susceptible to clindamycin.

Anti-Bacterial Agents↗

Adrenal masses: mr imaging features with pathologic correlation.

The detection of adrenal lesions has increased with the expanding use of cross-sectional imaging. Magnetic resonance (MR) imaging is often useful for characterizing adrenal masses. Adrenal masses can be classified into various groups on the basis of the presence of intracellular lipid, macroscopic fat, hemorrhage, and cystic changes and the vascularity and shape of the tumor. These imaging features can be used by the radiologist to suggest or confirm a diagnosis for most adrenal masses, including adenoma, hyperplasia, simple and complicated cysts, lymphangioma, myelolipoma, pheochromocytoma, hemorrhage, cortical carcinoma, neuroblastoma, lymphoma, and metastases. Adenomas and metastases are common, and a decrease in signal intensity on out-of-phase images can be used to differentiate between them. Carcinoma is a possible diagnosis if that decrease in signal intensity is heterogeneous. Benign disease is diagnosed if macroscopic fat or a homogeneous cystlike lesion is seen. Recognition of the typical MR imaging features is important because it often changes the treatment approach and may obviate surgery.

Adrenal Gland Diseases↗

Multiple measures of carcinoma extent versus perineural invasion in prostate needle biopsy tissue in prediction of pathologic stage in a screening population.

The capacity of perineural invasion by carcinoma in prostate needle biopsy tissue to independently predict pathologic stage in radical prostatectomy tissues remains uncertain. We sought to determine, in a prostate specific antigen-based screening population, the ability of needle biopsy histologic grade, tumor extent, and perineural invasion to independently predict pathologic stage and margin status in the whole prostate gland. Perineural invasion, Gleason grade, percentage Gleason pattern 4/5 carcinoma, and multiple measures of needle biopsy tumor extent, including number of positive cores, percentage of positive cores, total percentage of carcinoma, greatest percentage of carcinoma in a single core, and total carcinoma length in millimeters, were captured for 215 men from a prostate specific antigen-based screening program diagnosed with prostate cancer in a median of six procured needle biopsy cores. Pathologic stage and surgical margin status were evaluated in corresponding completely embedded radical prostatectomy specimens. A logistic regression model was used to relate the endpoints of extraprostatic extension by carcinoma and/or positive margins to needle biopsy tissue findings. In univariate analyses, total percentage of carcinoma (p = 0.003), greatest percentage of carcinoma in a single core (p = 0.004), total tumor length in millimeters (p = 0.009), and fraction of positive cores (p = 0.02) were all significantly associated with extraprostatic (pT3) carcinoma, whereas all five measures of carcinoma extent in needle biopsy tissue were related to positive margins. Correlation coefficient determinations showed that all five measures of needle biopsy carcinoma extent were highly interrelated. In multivariate analyses, total percentage of carcinoma was significantly related to pathologic T stage (p = 0.003) and positive margins (p = 0.0002). In a multivariate model with the radical prostatectomy whole gland endpoint of either pT3 disease or positive margins, fraction of positive cores (p = 0.00001) was the only variable with significant predictive value. Perineural invasion by carcinoma in needle biopsy tissue was detected in 11% of cases. Neither presence nor absence of perineural carcinoma nor number nor percentage of positive nerves related to pathologic stage in univariate or multivariate analyses. Amount of carcinoma in prostate needle biopsy tissue, using multiple measurements but not perineural invasion, is a significant histologic attribute predictive of pathologic stage and margin status for men with prostate specific antigen screening detected prostatic carcinoma. Reporting of several measures of carcinoma extent in needle biopsy tissue is recommended.

Adult↗

Clinical and microbiologic analysis of a hospital's extended-spectrum beta-lactamase-producing isolates over a 2-year period.

STUDY OBJECTIVE: To evaluate the microbiologic and clinical outcomes of patients with extended-spectrum beta-lactamase (ESBL)-producing isolates over a 2-year period. DESIGN: Retrospective analysis. SETTING: Tertiary care teaching hospital. PATIENTS: Twenty-one patients with cultures of confirmed ESBL-producing Escherichia coli, Klebsiella pneumoniae, or Klebsiella oxytoca. MEASUREMENTS AND MAIN RESULTS: Antimicrobial susceptibilities of piperacillin-tazobactam, cefotetan, carbapenems, aminoglycosides, fluoroquinolones, trimethoprim-sulfamethoxazole, and nitrofurantoin (nitrofurantoin for urinary isolates only) of confirmed ESBL producers at our institution were determined, as well as clinical outcomes of patients with ESBL-producing isolates. Microbiologic and medical records were reviewed for patient sex and age, antimicrobial susceptibilities, antimicrobial therapy, and clinical and microbiologic outcomes. From January 2000-December 2001, 31 isolates were confirmed as ESBL producers (6 E. coli, 11 K. pneumoniae, and 14 K. oxytoca). A statistically significant increase occurred over the 2-year period from 9 (0.6%) of 1414 isolates in 2000 to 22 (1.8%) of 1218 isolates in 2001 (p = 0.0055). All isolates were susceptible to carbapenems, and more than 88% were susceptible to amikacin, cefotetan, or nitrofurantoin. Less than 70% of isolates were susceptible to gentamicin, fluoroquinolones, piperacillin-tazobactam, or trimethoprim-sulfamethoxazole. All patients treated with a carbapenem experienced clinical cure. Piperacillin-tazobactam alone and in combination resulted in an overall clinical cure rate of 55%, with a 50% cure rate for isolates susceptible to piperacillin-tazobactam. All patients in whom antibiotic therapy failed had been treated with piperacillin-tazobactam or cefepime, either alone or in combination with a fluoroquinolone. CONCLUSION: Carbapenems remain the treatment of choice for ESBL-producing pathogens. Piperacillin-tazobactam and cefepime should not be routinely administered for the treatment of these organisms.

Anti-Bacterial Agents↗

Carcinoma extent in prostate needle biopsy tissue in the prediction of whole gland tumor volume in a screening population.

Increasing prostate tumor volume has been shown to correlate with numerous adverse prognostic indicators for patients with prostate carcinoma The ability to predict tumor volume from pretreatment parameters is potentially critical in the stratification of patients for different management strategies. We assessed the capacity of preoperative variables to predict tumor volume in 100 men diagnosed with prostate cancer in a prostate-specific antigen (PSA)-based screening program. Preoperative information included total serum PSA concentration and needle biopsy tissue variables, including Gleason score, number of positive cores, linear extent of carcinoma in millimeters, greatest percentage of carcinoma (in a single core), total percentage of carcinoma (all cores), presence of perineural invasion, and percentage of high-grade carcinoma. The postoperative end point was total tumor volume in radical prostatectomy tissue, calculated by image analysis. We determined independently significant factors and generated a predictive modelfor whole gland tumor volume. Total tumor volume was related significantly in multivariate analysis to 3 preoperative variables: linear extent of carcinoma, exponential number of positive cores, and serum PSA. A predictive model generated based on these 3 variables accounted for only 65% of the natural deviance of the data owing to data-point scatter for individual patients, suggesting that additional variables are needed to more accurately predict tumor volume. Findings highlight the importance of reporting quantitative measures of tumor amount in prostate needle biopsy specimens; several measures of tumor extent (vs 1 measure) provide maximal information on prostate cancer size.

Adenocarcinoma↗

PCR for the diagnosis of toxoplasmosis after hematopoietic stem cell transplantation.

Toxoplasma gondii is a ubiquitous pathogen that causes significant morbidity and mortality in immunocompromised patients. Although relatively uncommon, toxoplasmosis is increasingly recognized as a severe complication of hematopoietic stem cell transplantation. Timely and accurate diagnosis of this treatable infection is critical. PCR-based testing has become the preferred method for diagnosis, occasionally replacing tissue biopsy. This article reviews the clinical, diagnostic and therapeutic aspects of toxoplasmosis in the setting of hematopoietic stem cell transplantation and the current and future role of PCR-based testing for early detection and diagnosis.

Animals↗