Propensity score analysis of 18-FDG PET/CT-enhanced staging in patients undergoing surgery for esophageal cancer.

PURPOSE: PET/CT is now integral to the staging pathway for potentially curable esophageal cancer (EC), primarily to identify distant metastases undetected by computed tomography. The aim of this study was to analyze the effect of PET/CT introduction on survival and assess patterns of recurrence after esophagectomy. METHODS: A longitudinal cohort of EC patients staged between 1998 and 2016 were considered for inclusion. After co-variate adjustment using propensity scoring, a cohort of 496 patients (273 pre-PET/CT and 223 post-PET/CT) who underwent esophagectomy [median age 63 years (31-80), 395 males, 425 adenocarcinomas, 71 squamous cell carcinomas, 325 neoadjuvant therapy] were included. The primary outcome measure was overall survival (OS) based on intention to treat. RESULTS: Three-year OS pre-PET/CT was 42.5% compared with 57.8% post-PET/CT (Chi2 6.571, df 1, p = 0.004). On multivariable analysis, pT stage (HR 1.496 [95% CI 1.28-1.75], p < 0.0001), pN stage (HR 1.114 [95% CI 1.04-1.19], p = 0.001) and PET/CT staging (HR 0.688 [95% CI 0.53-0.89] p = 0.004) were independently associated with OS. Recurrent cancer was observed in 125 patients (51.4%) pre-PET/CT, compared with 74 patients post-PET/CT (37.8%, p = 0.004), and was less likely to be distant recurrence after PET/CT introduction (39.5 vs. 27.0%, p = 0.006). CONCLUSIONS: Enhanced PET/CT staging is an important modality and independent factor associated with improved survival in patients undergoing esophagectomy for cancer.

Propensity Score Analysis of an Enhanced Recovery Programme in Upper Gastrointestinal Cancer Surgery.

INTRODUCTION: The aim of this study was to examine the influence of an enhanced recovery programme (ERP) on outcomes of upper gastrointestinal (UGI) cancer surgery by means of propensity score-matched analysis. METHODS: Three hundred consecutive patients diagnosed with UGI cancer were studied prospectively before and after the introduction of an ERP. Multiple regression models, including propensity scores, were developed to assess confounding variables associated with undergoing surgery, and the risk adjusted association between treatment and length of hospital stay (LOHS). RESULTS: After regression for confounding factors, a cohort of 252 patients was available of whom 160 received ERP [median age 66 years (IQR 58-73), 119 male, 81 oesophageal, 79 gastric cancer] and 92 control [66 years (IQR 58-74), 74 male, 58 oesophageal, 34 gastric cancer]. ERP operative morbidity (Clavien-Dindo ≥3) and mortality were 13.8 and 3.1 % compared with 17.4 (p = 0.449) and 2.2 % (p = 0.658) in controls. Median ERP critical care and total LOS were 1 (IQR 0-1) and 13 (IQR 10-17) days, compared with 1 (IQR 1-2, p = 0.009) and 16 (IQR 13-26, p < 0.001) days. Multivariable analysis revealed ERP (HR 1.477, 95 % CI 1.084-2.013, p = 0.013), tumour location (HR 2.420, 95 % CI 1.624-3.606, p < 0.001), operative procedure (HR 1.143, 95 % CI 1.032-1.265, p = 0.010), and operative morbidity (HR 0.277, 95 % CI 0.179-0.429, p < 0.001) to be associated with LOHS. CONCLUSION: An ERP in UGI cancer surgery was feasible, safe, and effective.

The Reed-Stanton press rig for the generation of reproducible fingermarks: Towards a standardised methodology for fingermark research.

In the search for better or new methods/techniques to visualise fingermarks or to analyse them exploiting their chemical content, fingermarks inter-variability may hinder the assessment of the method effectiveness. Variability is due to changes in the chemical composition of the fingermarks between different donors and within the same donor, as well as to differential contact time, pressure and angle. When validating a method or comparing it with existing ones, it is not always possible to account for this type of variability. One way to compensate for these issues is to employ, in the early stages of the method development, a device generating reproducible fingermarks. Here the authors present their take on such device, as well as quantitatively describing its performance and benefits against the manual production of marks. Finally a short application is illustrated for the use of this device, at the method developmental stages, in an emerging area of fingerprinting research concerning the retrieval of chemical intelligence from fingermarks.

Safety of maintaining elective and emergency surgery during the COVID-19 pandemic with the introduction of a Protected Elective Surgical Unit (PESU): A cross-specialty evaluation of 30-day outcomes in 9,925 patients undergoing surgery in a University Health Board.

Background: The COVID-19 pandemic has caused unprecedented health care challenges mandating surgical service reconfiguration. Within our hospital, emergency and elective streams were separated and self-contained Protected Elective Surgical Units were developed to mitigate against infection-related morbidity. Aims of this study were to determine the risk of COVID-19 transmission and mortality and whether the development of Protected Elective Surgical Units can result in significant reduction in risk. Methods: A retrospective observational study of consecutive patients from 18 specialties undergoing elective or emergency surgery under general, spinal, or epidural anaesthetic over a 12-month study period was undertaken. Primary outcome measures were 30-day postoperative COVID-19 transmission rate and mortality. Secondary adjusted analyses were performed to ascertain hospital and Protected Elective Surgical Unit transmission rates. Results: Between 15 March 2020 and 14 March 2021, 9,925 patients underwent surgery: 6,464 (65.1%) elective, 5,116 (51.5%) female, and median age 57 (39-70). A total of 69.5% of all procedures were performed in Protected Elective Surgical Units. Overall, 30-day postoperative COVID-19 transmission was 2.8% (3.4% emergency vs 1.2% elective P < .001). Protected Elective Surgical Unit postoperative transmission was significantly lower than non-Protected Elective Surgical Unit (0.42% vs 3.2% P < .001), with an adjusted likely in-hospital Protected Elective Surgical Unit transmission of 0.04%. The 30-day all-cause mortality was 1.7% and was 14.6% in COVID-19-positive patients. COVID-19 infection, age > 70, male sex, American Society of Anesthesiologists grade > 2, and emergency surgery were all independently associated with mortality. Conclusion: This study has demonstrated that Protected Elective Surgical Units can facilitate high-volume elective surgical services throughout peaks of the COVID-19 pandemic while minimising viral transmission and mortality. However, mortality risk associated with perioperative COVID-19 infection remains high.

Value of individual surgeon performance metrics as quality assurance measures in oesophagogastric cancer surgery.

BACKGROUND: Surgeon-level operative mortality is widely seen as a measure of quality after gastric and oesophageal resection. This study aimed to evaluate this alongside a compound-level outcome analysis. METHODS: Consecutive patients who underwent treatment including surgery delivered by a multidisciplinary team, which included seven specialist surgeons, were studied. The primary outcome was death within 30 days of surgery; secondary outcomes were anastomotic leak, Clavien-Dindo morbidity score, lymph node harvest, circumferential resection margin (CRM) status, disease-free (DFS), and overall (OS) survival. RESULTS: The median number of annual resections per surgeon was 10 (range 5-25), compared with 14 (5-25) for joint consultant teams (P = 0·855). The median annual surgeon-level mortality rate was 0 (0-9) per cent versus an overall network annual operative mortality rate of 1·8 (0-3·7) per cent. Joint consultant team procedures were associated with fewer operative deaths (0·5 per cent versus 3·4 per cent at surgeon level; P = 0·027). The median surgeon anastomotic leak rate was 12·4 (range 9-20) per cent (P = 0·625 versus the whole surgical range), overall morbidity 46·5 (31-60) per cent (P = 0·066), lymph node harvest 16 (9-29) (P < 0·001), CRM positivity 32·0 (16-46) per cent (P = 0·003), 5-year DFS rate 44·8 (29-60) per cent and OS rate 46·5 (35-53) per cent. No designated metrics were independently associated with DFS or OS in multivariable analysis. CONCLUSION: Annual surgeon-level metrics demonstrated wide variations (fivefold), but these performance metrics were not associated with survival.

ANTECEDENTES: La mortalidad operatoria relacionada con el nivel del cirujano se contempla ampliamente como una medida de calidad tras la resección esofágica. Este estudio tenía como objetivo evaluar este aspecto junto con un análisis de resultados conjuntos a nivel de procedimientos. MÉTODOS: Se estudiaron los pacientes consecutivos que fueron tratados, incluyendo el tratamiento quirúrgico, efectuado por un equipo multidisciplinar formado por siete cirujanos especialistas. La variable principal de resultados era la mortalidad a durante los primeros 30 días de la cirugía, y las variables secundarias fueron la fuga anastomótica, la gravedad de la puntuación de morbilidad de Clavien-Dindo, el número de ganglios linfáticos obtenidos, el estado del margen circunferencial (circumferential margin, CRM), la supervivencia libre de enfermedad (disease-free survival, DFS) y la supervivencia global (overall survival, OS). RESULTADOS: La mediana del número anual de resecciones por cirujano fue de 10 (rango 5-25, P = 0,855). El nivel de la mediana de mortalidad anual por cirujano fue del 0% (0-9,1) y la mortalidad operatoria anual global del equipo de 1,8% (0-3,7, P = 0,389). Los procedimientos conjuntos del equipo consultor se asociaron con menos muertes operatorias (0,5 versus 3,4%, P = 0,027). La tasa mediana (rango) de fuga anastomótica por cirujano fue del 12% (9-20, P = 0,625), la morbilidad global del 46,7% (31-60, P = 0,003), la DFS a los 5 años del 44,8% (28,6-60,0, P = 0,257) y la OS del 46,5% (35,0-52,5, P = 0,573). Ningún factor mostró una asociación independiente con la DFS o la OS en el análisis multivariable. CONCLUSIÓN: Las medidas anuales a nivel de cirujano demostraron amplias variaciones (9 veces), pero estas medidas de rendimiento no se asociaron con la supervivencia.

Association between foot type and tibial stress injuries: a systematic review.

OBJECTIVES: To systematically review published articles investigating the association between structural foot characteristics and tibial stress injuries, and to suggest possible future avenues of research in this area. METHODS: Literature was identified, selected and appraised in accordance with the methods of a systematic review. Articles potentially relevant to the research question were identified by searching the following electronic databases: Amed, Cinahl, Index to UK theses, Medline, PubMed, Scopus, Sports discus and Web of science. Duplicates were removed and, based on the title and abstract, the full text of relevant studies were retrieved. Two reviewers independently assessed papers; this formed the basis for the inclusion of the most appropriate trials. RESULTS: From the 479 articles originally identified, nine were deemed appropriate for inclusion in the review. In general, specific data relating to this relationship was limited. Outcomes of the nine investigations were difficult to compare due to differing methods used across studies. Results have proved conflicting, with limited evidence found to implicate any specific foot type as a potential risk factor for tibial stress injuries. CONCLUSIONS: No definitive conclusions can be drawn relating foot structure or function to an increased risk of tibial stress injuries. Extremes of foot types are likely to pose an increased risk of tibial stress injuries compared to normal arched feet.

Antigen and antibody testing for the diagnosis of blastomycosis in dogs.

BACKGROUND: Early diagnosis and treatment are associated with an improved prognosis in blastomycosis. The diagnosis of blastomycosis may be missed by cytology, histopathology, culture, or serology. An enzyme immunoassay (EIA) for detection of Blastomyces dermatitidis galactomannan antigen in body fluids has been used for rapid diagnosis of blastomycosis in humans. HYPOTHESIS: Measurement of Blastomyces antigen in urine or serum by the MVista Blastomyces antigen EIA is more sensitive than measurement of anti-Blastomyces antibodies for diagnosis of blastomycosis in dogs. METHODS: Serum and urine samples from 46 dogs with confirmed blastomycosis were tested for Blastomyces antigen and serum was tested for anti-Blastomyces antibodies. RESULTS: The sensitivity for the detection of antigen in urine was 93.5% and it was 87.0% in serum. The sensitivity of antibody detection by agar gel immunodiffusion (AGID) was 17.4% and it was 76.1% by EIA. Antigen and antibody decreased during itraconazole treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Antigen detection is a more sensitive test for diagnosis of blastomycosis than antibody testing by AGID, the only commercially available method. Antigen concentrations decreased with treatment.

The use of consumer depth cameras for 3D surface imaging of people with obesity: A feasibility study.

OBJECTIVE: Three dimensional (3D) surface imaging is a viable alternative to traditional body morphology measures, but the feasibility of using this technique with people with obesity has not been fully established. Therefore, the aim of this study was to investigate the validity, repeatability and acceptability of a consumer depth camera 3D surface imaging system in imaging people with obesity. METHODS: The concurrent validity of the depth camera based system was investigated by comparing measures of mid-trunk volume to a gold-standard. The repeatability and acceptability of the depth camera system was assessed in people with obesity at a clinic. RESULTS: There was evidence of a fixed systematic difference between the depth camera system and the gold standard but excellent correlation between volume estimates (r2=0.997), with little evidence of proportional bias. The depth camera system was highly repeatable - low typical error (0.192L), high intraclass correlation coefficient (>0.999) and low technical error of measurement (0.64%). Depth camera based 3D surface imaging was also acceptable to people with obesity. CONCLUSION: It is feasible (valid, repeatable and acceptable) to use a low cost, flexible 3D surface imaging system to monitor the body size and shape of people with obesity in a clinical setting.

Murine laminin binds to Histoplasma capsulatum. A possible mechanism of dissemination.

Histoplasmosis, an increasingly important opportunistic infection in immunosuppressed subjects, is characterized by hematogenous dissemination of the yeast from the lung. The mechanism of this dissemination is not fully understood. Laminin, the major glycoprotein of the extracellular matrix, is known to mediate the attachment of various invasive pathogens to host tissues. In the current study, laminin is demonstrated to bind to Histoplasma capsulatum in a rapid, specific, and saturable manner. Scatchard analysis with 125I-labeled laminin revealed an estimated 3.0 x 10(4) binding sites per yeast with an apparent Kd for laminin binding of 1.6 x 10(-9) M. Laminin binding to H. capsulatum was decreased from 62 +/- 1 to 17 +/- 1 ng (P < 0.001) in the presence of 3,000 nM of Ile-Lys-Val-Ala-Val, a pentapeptide within one major cell attachment site of laminin. A 50-kD H. capsulatum laminin-binding protein was demonstrated using an 125I-Ln blot of H. capsulatum cell wall proteins. The 50-kD protein is also recognized by antibodies directed at the 67-kD laminin receptor, suggesting they are related. This study proposes a possible mechanism for H. capsulatum attachment to laminin, an important first step required for the yeast to recognize and traverse the basement membrane.

The accuracy of breast volume measurement methods: A systematic review.

Breast volume is a key metric in breast surgery and there are a number of different methods which measure it. However, a lack of knowledge regarding a method's accuracy and comparability has made it difficult to establish a clinical standard. We have performed a systematic review of the literature to examine the various techniques for measurement of breast volume and to assess their accuracy and usefulness in clinical practice. Each of the fifteen studies we identified had more than ten live participants and assessed volume measurement accuracy using a gold-standard based on the volume, or mass, of a mastectomy specimen. Many of the studies from this review report large (>200 ml) uncertainty in breast volume and many fail to assess measurement accuracy using appropriate statistical tools. Of the methods assessed, MRI scanning consistently demonstrated the highest accuracy with three studies reporting errors lower than 10% for small (250 ml), medium (500 ml) and large (1000 ml) breasts. However, as a high-cost, non-routine assessment other methods may be more appropriate.

Cerebrospinal fluid Histoplasma antibodies in central nervous system histoplasmosis.

We have evaluated the Histoplasma antibody response in the cerebrospinal fluid (CSF) in nine patients with central nervous system histoplasmosis and 98 controls. While the CSF Histoplasma antibody response identified eight of the nine patients, CSF cultures were positive in only two. Of controls with histoplasmosis but without meningitis (13 patients), or without histoplasmosis (85 patients), elevated CSF antibodies were detected by complement fixation in seven, by IgG radioimmunoassay in 17, and by IgM radioimmunoassay in five. Measurement of the CSF Histoplasma antibody response appears useful for identifying meningitis in patients with histoplasmosis, although cross-reactions occur in half of patients with other forms of chronic fungal meningitis. Patients with these other infections can usually be identified by tests for CSF Coccidioides antibodies, or cryptococcal antigens.

Commercially available (ENDO-STAPH) assay for teichoic acid antibodies. Evaluation in patients with serious Staphylococcus aureus infections and in controls.

We have evaluated the clinical usefulness of a commercially available teichoic acid antibody assay (ENDO-STAPH). Teichoic acid antibody titers up to a 1:2 serum dilution were observed in 20% of normal subjects, thus, titers of 1:4 or more were considered positive. Of patients with Staphylococcus aureus infections, 16 of 23 with endocarditis, 12 of 20 with complicated bacteremia, three of 17 with uncomplicated bacteremia, and ten of 20 with nonbacteremic infections had positive titers. Only four of 70 controls had positive titers. Results agreed with those using our standard assay in 130 of 151 specimens. Results were reproducibly positive or negative in 17 of 18 specimens that were retested. Results were also reproducible in ten specimens retested using a different lot of standardized antigen. The ENDO-STAPH assay should broaden the clinical applications of assays for TAA.

Histoplasmosis. Experience during outbreaks in Indianapolis and review of the literature.

Histoplasmosis remains a common infection in endemic regions of North America and Latin America, causing a broad spectrum of clinical findings. Experience during recurrent outbreaks in Indianapolis has shown the importance of immunosuppressive conditions including the acquired immunodeficiency syndrome (AIDS) as a risk factor for disseminated disease and expanded our knowledge of the common clinical manifestations. Pericarditis, rheumatologic manifestations, esophageal compression, and sarcoidlike manifestations were found to be relatively common findings in histoplasmosis. These studies have established the useful role of serologic testing and have led to the discovery of antigen testing for diagnosis of histoplasmosis. This experience also has offered the opportunity to examine the outcome of treatment in persons with AIDS, contributing to studies that have found itraconazole to be an excellent alternative to amphotericin B in persons with mild or moderately severe infection.

Clinical and laboratory features of disseminated histoplasmosis during two large urban outbreaks.

Clinical and laboratory features have been reviewed in 66 episodes of disseminated histoplasmosis that occurred during two large urban outbreaks in Indianapolis. Immunosuppression, age greater than 54 years, and presence of other serious underlying illnesses predisposed to the disseminated form of the disease; only 21% of patients lacked one of these risk factors. Central nervous system findings, splenomegaly, hepatomegaly, and lymphopenia suggested disseminated disease but were present in only about one-third of patients. Miliary or diffuse pulmonary infiltrates also suggested dissemination and were noted in about one-third of patients, while mediastinal lymphadenopathy was present in only 17%. Histoplasmal serologic tests, positive in 90% of patients, provided useful diagnostic clues. The diagnosis could be confirmed by culture in 88% of patients, and special stains were positive in about two-thirds. Although 10% of patients recovered without treatment, 11 patients (17%) died because of failure to suspect the diagnosis and initiate therapy promptly. Amphotericin B was effective in all patients receiving at least 500 mg, but relapse occurred if the total dose was less than 30 mg/kg. Ketoconazole appeared effective in non-immunosuppressed patients but not in those with underlying immunosuppression; however, a controlled trial comparing ketoconazole and amphotericin B is required to establish the role of this new fungistatic oral agent.

Diagnostic strategies in osteomyelitis.

Technetium-99 (99Tc) pyrophosphate bone scanning often identifies patients with osteomyelitis before roentgenographic findings appear. However, recent studies have shown that 99Tc bone scanning often gives false-negative results, especially in neonates. The accuracy of computed tomographic scanning and indium-111 leukocyte scanning for diagnosis of early osteomyelitis has not been established. 99Tc bone scanning often gives false-positive results in patients with other conditions leading to bone injury and repair, such as trauma or recent surgery, further limiting the usefulness of this imaging procedure. Newer imaging techniques have not been adequately evaluated to establish their specificity. Because of their high cost and unproved accuracy, these new imaging procedures should not be routinely applied until their usefulness has been established. Bone biopsy remains the procedure of choice for establishing the diagnosis in patients suspected clinically to have osteomyelitis with negative findings on roentgenography and 99Tc bone scanning. Although Staphylococcus aureus is the leading cause of osteomyelitis, other pathogens cause 30 to 40 percent of cases. Aspiration or biopsy of the involved bone is usually required to choose appropriate antibiotic therapy. Bone biopsy is essential in chronic osteomyelitis, since cultures of sinus drainage are unreliable. Osteomyelitis in diabetics with foot infection and in association with decubitus ulcers presents special problems. Radionuclide scanning often give false-positive results in these patients. Proper diagnosis usually requires careful assessment of clinical and roentgenographic findings. Although bone biopsy seems useful in diagnosing osteomyelitis underlying decubitus ulcers, its role in diabetic patients with foot infections is not established. I do not recommend biopsy of foot bones in diabetic patients, since culture of bone biopsy specimens often give unreliable results in these situations because of contamination with ulcer organisms.

Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trial Group.

PURPOSE: Amphotericin B has been the treatment of choice for disseminated histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS). Oral antifungal agents would be welcome alternatives to standard treatment of disseminated histoplasmosis in less severe cases. The purpose of this study was to assess the efficacy and safety of itraconazole therapy in patients with AIDS and disseminated histoplasmosis. PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomized prospective trial conducted in university hospitals of the AIDS Clinical Trial Group. All patients had AIDS and first episodes of disseminated histoplasmosis. Patients with central nervous system involvement or with severe clinical manifestations were excluded. Patients were treated with itraconazole BID by mouth 300 mg for 3 days and then 200 mg BID for 12 weeks. Resolution of clinical findings, clearance of positive cultures, and drug tolerance were the main outcome measurements. A secondary objective was effect of therapy on Histoplasma capsulatum var capsulatum antigen levels. RESULTS: Of 59 evaluable patients, 50 (85%) responded to therapy. Five patients withdrew because of progressive infection, 1 died of a presumed pulmonary embolus within the first week of therapy without improvement, 2 withdrew because of toxicity, and 1 was lost to follow-up after week 2 of therapy. Patients with moderately severe clinical (fever > 39.5 degrees C or Karnofsky score < 60) or laboratory abnormalities (alkaline phosphatase > 5 times normal or albumin < 3 g/dL) at baseline tended to respond more poorly than did other patients. Resolution of complaints of fever and improvement in fatigue occurred after a median of 3 and 6 weeks, respectively, and weight gain after 2 weeks. Fungemia cleared after a median of 1 week. H capsulatum var capsulatum antigen cleared from the urine and serum at rates of 0.2 and 0.3 units per week, respectively. CONCLUSIONS: Itraconazole is safe and effective induction therapy for mild disseminated histoplasmosis in patients with AIDS, offering an alternative to amphotericin B in such cases. Patients with moderately severe or severe histoplasmosis should first be treated with amphotericin B and then may be switched to itraconazole after achieving clinical improvement.

Prevention of relapse of histoplasmosis with fluconazole in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To assess the effectiveness of fluconazole for suppression of relapse of histoplasmosis in patients with acquired immunodeficiency syndrome (AIDS). DESIGN: Retrospective, nonrandomized, open trial. SETTING: Multicenter at two university referral centers and in five private practices. PATIENTS: Seventy-six patients with AIDS and disseminated histoplasmosis who completed induction treatment with amphotericin B, itraconazole, or fluconazole and maintained on treatment with fluconazole to prevent relapse. INTERVENTIONS: Fluconazole was given at dosages of 100 to 400 mg per day. Patients were followed by their primary physicians, who completed questionnaires collecting information about treatment and relapse status. Blood and urine specimens were submitted periodically for Histoplasma capsulatum var. capsulatum antigen determination. MEASUREMENTS AND MAIN RESULTS: Nine of the 76 patients relapsed during fluconazole therapy and another was removed from the study because of allergic rash. Survival after initiation of therapy for histoplasmosis was 94 weeks, ranging from 74 weeks for those who received less than 1 g of amphotericin B for induction and none for maintenance therapy to 156 weeks for those who received greater than 1 g for induction and additional amphotericin B for maintenance therapy before beginning fluconazole (P < 0.02). Antigen levels fell at rates of 0.05 units/week in urine and 0.02 units/week in serum in patients who were successfully maintained in remission and increased by > or = 2 units/week in 4 of 6 patients who relapsed. CONCLUSIONS: Fluconazole > or = 200 mg daily is a reasonable choice for chronic suppressive therapy of histoplasmosis in patients who cannot take itraconazole because of drug interactions, malabsorption, or side effects.

Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group.

PURPOSE: This study assesses the efficacy and safety of fluconazole therapy in patients with acquired immunodeficiency syndrome (AIDS) and mild to moderately severe manifestations of disseminated histoplasmosis. PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomized prospective trial. All patients had AIDS and disseminated histoplasmosis. Patients were treated with 1,200 mg of fluconazole given by mouth once on the first day, then 600 mg once daily for 8 weeks, and those patients who improved clinically were then assigned fluconazole maintenance therapy 200 mg once daily for at least 1 year. Interim analysis revealed a high failure rate (10 of 20, 50%), causing revision of the protocol to increase the fluconazole dose to 1,600 mg given once on the first day, then 800 mg once daily, and the duration to 12 weeks for induction therapy and then 400 mg daily for 1 year for maintenance therapy. MEASUREMENTS AND MAIN RESULTS: Thirty-six of 49 patients (74%; 95% confidence interval [CI]: 59% to 85%) with mild to moderately severe clinical manifestations who entered into the revised study responded to 800 mg of fluconazole daily for 12 weeks as induction therapy. Of the seven patients who failed induction therapy because of progression of histoplasmosis, one died of the infection. Of 36 patients who entered into the maintenance phase of the study receiving 400 mg of fluconazole daily for 1 year, 11 (30.5%) relapsed, including one who died (2.8%). Two of the 49 patients (4.1%) were removed because of grade 4 adverse events, alkaline phosphatase elevation for one and aspartate aminotransferase elevation in the other. The relapse-free rate at 1 year was 53% (95% CI: 32% to 89%), prompting closure of the study. CONCLUSIONS: Fluconazole 800 mg daily is a safe and moderately effective induction therapy for mild or moderately severe disseminated histoplasmosis in patients with AIDS. On the basis of historic comparison, fluconazole 400 mg daily is less effective than itraconazole 200 to 400 mg daily or amphotericin B 50 mg given weekly as maintenance therapy to prevent relapse.

Objective decision-making following a portal film: the results of a pilot study.

PURPOSE: To discriminate between random and systematic treatment setup errors using portal films. METHODS AND MATERIALS: A bi-dimensional analytic techniques using multiple analyses of variance based on Hotelling's T2 statistics to derive numerical and graphical measures of daily portal film accuracy and precision has been trialed using 88 daily portal films from seven patients' treatment. RESULTS: A demonstration is provided of how a reasonable approximation of random variation from the intended (Simulator) field center, and systematic displacement of the mean position of the portal film centers may be derived from a minimum number of portal films. If a random error as great as 10 mm exists, at least six or seven portal films are considered necessary to reliably detect and quantify the size of a systematic error. CONCLUSION: Our results suggest that a modest systematic error could go undetected until the end of a 5 or 6 week course of treatment if only one portal film is obtained each week. A greater number of portal films should be performed during the first week of treatment to reduce the frequency of such errors. Efforts to separate and quantify both random and systematic errors in setup are worthwhile and will lead to improvements in outcome at the individual patient level and at a departmental level in the development of quality assurance programs.

Multiple tactile maps in the human cerebellum.

Functional imaging studies of the cerebellum have mostly investigated motor performance or have been limited to the anterior lobe and therefore the somatosensory representations in the human cerebellum have not been fully demonstrated. We used fMRI of the entire cerebellum during tactile stimulation of the hand and foot in six normal subjects. Our results demonstrate that the tactile projections to the cerebellum in humans are represented in both the anterior and posterior lobes. in agreement with previous functional imaging studies, our results show a large-scale, between-limb somatotopy comparable to that shown in early animal studies.