Whole genome sequencing analysis of Mycobacterium tuberculosis reveals circulating strain types and drug-resistance mutations in the Philippines.

The Philippines is a high-incidence country for tuberculosis, with the increasing prevalence of multi- (MDR-TB) and extensively-drug (XDR-TB) resistant Mycobacterium tuberculosis strains posing difficulties to disease control. Understanding the genetic diversity of circulating strains can provide insights into underlying drug resistance mutations and transmission dynamics, thereby assisting the design of diagnostic tools, including those using next generation sequencing (NGS) platforms. By analysing genome sequencing data of 732 isolates from Philippines drug-resistance survey collections spanning from 2011 to 2019, we found that the majority belonged to lineages L1 (531/732; 72.5%) and L4 (European-American; n = 174; 23.8%), with the Manila strain (L1.2.1.2.1) being the most prominent (475/531). Approximately two-thirds of isolates were found to be at least MDR-TB (483/732; 66.0%), and potential XDR-TB genotypic resistance was observed (3/732; 0.4%), highlighting an emerging problem in the country. Genotypic resistance was highly concordant with laboratory drug susceptibility testing. By finding isolates with (near-)identical genomic variation, five major clusters containing a total of 114 isolates were identified: all containing either L1 or L4 isolates with at least MDR-TB resistance and spanning multiple years of collection. Closer inspection of clusters revealed transmission in prisons, some involving isolates with XDR-TB, and mutations linked to third-line drug bedaquiline. We have also identified previously unreported mutations linked to resistance for isoniazid, rifampicin, ethambutol, and fluoroquinolones. Overall, this study provides important insights into the genetic diversity, transmission and circulating drug resistance mutations of M. tuberculosis in the Philippines, thereby informing clinical and surveillance decision-making, which is increasingly using NGS platforms.

Estimation of country-specific tuberculosis resistance antibiograms using pathogen genomics and machine learning.

BACKGROUND: Global tuberculosis (TB) drug resistance (DR) surveillance focuses on rifampicin. We examined the potential of public and surveillance Mycobacterium tuberculosis (Mtb) whole-genome sequencing (WGS) data, to generate expanded country-level resistance prevalence estimates (antibiograms) using in silico resistance prediction. METHODS: We curated and quality-controlled Mtb WGS data. We used a validated random forest model to predict phenotypic resistance to 12 drugs and bias-corrected for model performance, outbreak sampling and rifampicin resistance oversampling. Validation leveraged a national DR survey conducted in South Africa. RESULTS: Mtb isolates from 29 countries (n=19 149) met sequence quality criteria. Global marginal genotypic resistance among mono-resistant TB estimates overlapped with the South African DR survey, except for isoniazid, ethionamide and second-line injectables, which were underestimated (n=3134). Among multidrug resistant (MDR) TB (n=268), estimates overlapped for the fluoroquinolones but overestimated other drugs. Globally pooled mono-resistance to isoniazid was 10.9% (95% CI: 10.2-11.7%, n=14 012). Mono-levofloxacin resistance rates were highest in South Asia (Pakistan 3.4% (0.1-11%), n=111 and India 2.8% (0.08-9.4%), n=114). Given the recent interest in drugs enhancing ethionamide activity and their expected activity against isolates with resistance discordance between isoniazid and ethionamide, we measured this rate and found it to be high at 74.4% (IQR: 64.5-79.7%) of isoniazid-resistant isolates predicted to be ethionamide susceptible. The global susceptibility rate to pyrazinamide and levofloxacin among MDR was 15.1% (95% CI: 10.2-19.9%, n=3964). CONCLUSIONS: This is the first attempt at global Mtb antibiogram estimation. DR prevalence in Mtb can be reliably estimated using public WGS and phenotypic resistance prediction for key antibiotics, but public WGS data demonstrates oversampling of isolates with higher resistance levels than MDR. Nevertheless, our results raise concerns about the empiric use of short-course fluoroquinolone regimens for drug-susceptible TB in South Asia and indicate underutilisation of ethionamide in MDR treatment.

A value-based healthcare model for initiating and switching psoriasis therapies-Results from the prospective multicentre IMPROVE study.

BACKGROUND: Little is known about the therapeutic benefits of a value-based healthcare model compared to a traditional activity-based incentive model in psoriasis (PsO). OBJECTIVES: This prospective non-interventional study evaluated an outcome-based, patient-centred management model for patients with PsO. METHODS: In total, 49 patients with a Psoriasis Area and Severity Index (PASI) ≥3 who were starting or switching between treatments were included. Patients were assessed at baseline, 3 and 9 months. The patient benefit index (PBI) was calculated using predefined questionnaires. An expected PBI was calculated and adjusted for risk factors known to complicate treatment, that is overweight and smoking. The model remunerated the department on whether the observed PBI exceeded the expected PBI to incentivize over-performance. RESULTS: In total, 40 patients (80%) completed all three visits; 32.7% were smokers and 73.5% were overweight. Mean PASI at baseline was 11.5 (SD 9.1); PASI improved significantly from baseline through 3 months: mean reduction, 8.0 (SD 9.2), p < 0.001 and was maintained until 9 months: mean further reduction, 0.1 (SD 3.3), p = 0.893. The mean PBI was 2.5 (SD 1.3) and 2.8 (SD 1.1) at 3 and 9 months, respectively. A PBI ≥1 was achieved by 87.8% at 3 and 95.1% at 9 months. Overall, the department was remunerated a mean 2721.1 DKK (SD 4472.8) per patient. In subgroup analysis, the department was remunerated a mean of, respectively, 2428.6 (SD 5089.5), 2636.6 (SD 4471.3) and 3196.5 (SD 4497.1) DKK for patients with none, 1 or 2 risk factors, that is smoking or/and overweight. CONCLUSIONS: The model evaluated herein is the first value-based model to calculate remuneration from patient reported outcomes and showed to successfully predict the expected PBI and remunerate treatment based on whether the expected treatment goal was met or exceeded. This can be utilized in the patient-centred management of PsO.

Lineage BA.2 dominated the Omicron SARS-CoV-2 epidemic wave in the Philippines.

The Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant led to a dramatic global epidemic wave following detection in South Africa in November 2021. The BA.1 Omicron lineage was dominant and responsible for most SARS-CoV-2 outbreaks in countries around the world during December 2021-January 2022, while other Omicron lineages, including BA.2, accounted for the minority of global isolates. Here, we describe the Omicron wave in the Philippines by analysing genomic data. Our results identify the presence of both BA.1 and BA.2 lineages in the Philippines in December 2021, before cases surged in January 2022. We infer that only the BA.2 lineage underwent sustained transmission in the country, with an estimated emergence around 18 November 2021 (95 per cent highest posterior density: 6-28 November), while despite multiple introductions, BA.1 transmission remained limited. These results suggest that the Philippines was one of the earliest areas affected by BA.2 and reiterate the importance of whole genome sequencing for monitoring outbreaks.

Molecular characterization of drug-resistant Mycobacterium tuberculosis among Filipino patients derived from the national tuberculosis prevalence survey Philippines 2016.

Tuberculosis, caused by Mycobacterium tuberculosis, remains a high burden disease and leading cause of mortality in the Philippines. Understanding the genetic diversity of M. tuberculosis strains in the population, including those that are multi-drug resistant (MDR), will aid in formulating strategies for effective TB control and prevention. By whole genome sequencing of M. tuberculosis isolates (n = 100) from patients of the Philippine 2016 National Tuberculosis Prevalence Survey, we sought to provide a baseline assessment of the genotypic and phylogenetic characteristics of the isolates. The majority (96/100) of the isolates were EAI2-Manila strain-type (lineage 1), with one Lineage 2 (Beijing), one Lineage 3 (CAS1), and two Lineage 4 (LAM9) strains. The EAI2-Manila clade was not significantly associated with patient's phenotypic and in silico drug resistance profile. Five (5/6) MDR-TB isolates predicted by in silico profiling were concordant with phenotypic drug resistance profile. Twenty-one mutations were identified in nine drug resistance-related genes, all of which have been reported in previous studies. Overall, the results from this study contribute to the growing data on the molecular characteristics of Philippine M. tuberculosis isolates, which can help in developing tools for rapid diagnosis of TB in the country, and thereby reducing the high burden of disease.

Mycobacterium tuberculosis whole genome sequencing provides insights into the Manila strain and drug-resistance mutations in the Philippines.

The Philippines has a high incidence of tuberculosis disease (TB), with an increasing prevalence of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains making its control difficult. Although the M. tuberculosis "Manila" ancient lineage 1 strain-type is thought to be prevalent in the country, with evidence of export to others, little is known about the genetic diversity of circulating strains. By whole genome sequencing (WGS) 178 isolates from the Philippines National Drug Resistance Survey, we found the majority (143/178; 80.3%) belonged to the lineage 1 Manila clade, with the minority belonging to lineages 4 (European-American; n = 33) and 2 (East Asian; n = 2). A high proportion were found to be multidrug-resistant (34/178; 19.1%), established through highly concordant laboratory drug susceptibility testing and in silico prediction methods. Some MDR-TB isolates had near identical genomic variation, providing potential evidence of transmission. By placing the Philippine isolates within a phylogeny of global M. tuberculosis (n > 17,000), we established that they are genetically similar to those observed outside the country, including a clade of Manila-like strain-types in Thailand. An analysis of the phylogeny revealed a set of ~200 SNPs that are specific for the Manila strain-type, and a subset can be used within a molecular barcode. Sixty-eight mutations known to be associated with 10 anti-TB drug resistance were identified in the Philippine strains, and all have been observed in other populations. Whilst nine putative streptomycin resistance conferring markers in gid (8) and rrs (1) genes appear to be novel and with functional consequences. Overall, this study provides an important baseline characterisation of M. tuberculosis genetic diversity for the Philippines, and will fill a gap in global datasets and aid the development of a nation-wide database for epidemiological studies and clinical decision making. Further, by establishing a molecular barcode for detecting Manila strains it will assist with the design of diagnostic tools for disease control activities.

Cause-specific mortality in patients with psoriasis and psoriatic arthritis.

BACKGROUND: There are limited data regarding causes of mortality in patients with psoriasis or psoriatic arthritis (PsA). OBJECTIVES: This retrospective cohort study evaluated the risk and leading causes of mortality in patients with psoriasis or PsA. METHODS: Individuals with a hospital-based diagnosis of PsA or psoriasis were identified using the Danish National Patient Registry. Matched control individuals were identified from the general population. The main outcome measures were risk of death and cause-specific mortality in patients with psoriasis or PsA. RESULTS: Death rates per 1000 patient-years (with 95% confidence intervals) vs. controls were 22·3 (19·7-24·9) vs. 13·9 (11·8-16·0) for patients with psoriasis and 10·8 (8·9-12·8) vs. 11·6 (9·6-13·6) for patients with PsA. Survival, according to stratified hazard ratios (HRs), was significantly lower in patients with psoriasis than in controls (HR 1·74, P < 0·001), but not in patients with PsA (HR 1·06, P = 0·19). Significantly increased risk of death was observed in patients with psoriasis vs. controls due to a number of causes; the highest risks were observed for diseases of the digestive system; endocrine, nutritional and metabolic diseases; and certain infectious and parasitic diseases (HRs 3·61, 3·02 and 2·71, respectively). In patients with PsA, increased mortality was observed only for certain infectious and parasitic diseases (HR 2·80) and diseases of the respiratory system (HR 1·46). Patients with psoriasis died at a younger age than controls (mean age 71·0 vs. 74·5 years, P < 0·001). CONCLUSIONS: Patients with severe psoriasis have increased mortality risk compared with matched controls, due to a number of causes. Evidence to support an increased risk for patients with PsA was less convincing.

Chronic urticaria in the real-life clinical practice setting in Sweden, Norway and Denmark: baseline results from the non-interventional multicentre AWARE study.

BACKGROUND: Chronic urticaria (CU) is characterized by the recurrence of itchy hives and/or angioedema for more than 6 weeks. AWARE (A World-wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) is a multinational study designed to document the real-life treatment situation, burden of disease and clinical resource usage of H1-antihistamine-refractory CU patients. OBJECTIVE: To examine baseline data from Scandinavian AWARE patients. METHODS: AWARE is a prospective, non-interventional, multinational, umbrella design study, which includes adults (≥18 years) with a confirmed CU diagnosis (>2 months) that is refractory to H1-antihistamines. Baseline patient characteristics, disease activity (urticaria control test [UCT]), pharmacological treatment, comorbidities and healthcare usage were documented by the treating physician. Quality of life (QoL; dermatology life quality index [DLQI]; chronic urticaria quality of life questionnaire [CU-Q2 oL; Danish patients only]) and work productivity and activity impairment (WPAI) scores were also assessed. RESULTS: Overall, 158 CU patients from seven centres in Denmark (n = 80), Norway (n = 50) and Sweden (n = 28) were included in this baseline analysis. Mean age and BMI were 40.3 years and 26.5 kg/m2 , respectively. The majority of patients were female (69.6%), had uncontrolled CU (75.6%; UCT score <12) and had a 'spontaneous' component to their CU (61.4% CSU; 20.3% both CSU and chronic inducible urticaria). Common comorbidities included asthma (19.6%), allergic rhinitis (16.5%) and food allergies (8.2%). Overall, 60.1% of patients reported using treatments for CU including non-sedative H1-antihistamines (40.5%), corticosteroids (19%), montelukast (14.6%) and omalizumab (8.2%). Pharmacological treatment rates increased to 96.2% during the baseline visit. On average, patient QoL was moderately affected (mean DLQI score 7.7) and healthcare resource usage was high. CONCLUSION: Adult Scandinavian H1-antihistamine-refractory CU patients reported high rates of healthcare usage and QoL impairment. Rates of pharmacological treatment use were low before study enrolment but increased to almost 100% during the baseline visit.

Poor sleep quality and obstructive sleep apnea in patients with GERD and Barrett's esophagus.

BACKGROUND: Gastroesophageal reflux disease (GERD) reduces sleep quality. Whether Barrett's esophagus (BE) affects sleep differently is unknown. Obstructive sleep apnea (OSA) often coexists with GERD and may disrupt sleep; whether GERD reduces sleep quality independently of OSA is unknown. Our aims were to compare the effect of GERD and BE on sleep quality, and assess the impact of OSA on this association. METHODS: Validated questionnaires for GERD symptoms, sleep quality, and OSA risk were prospectively administered to subjects undergoing upper endoscopy. GERD was defined by erosive esophagitis and/or reflux symptoms >1/week. BE was defined histologically. Controls had normal endoscopy and were asymptomatic. Poor sleep quality was defined by a Pittsburgh Sleep Quality Index score >5. Risk of OSA was defined by a positive Berlin Questionnaire. The risk poor sleep quality in GERD, BE, and controls was evaluated in multivariate models. KEY RESULTS: 83 GERD, 63 BE, and 75 controls were included. OSA and poor sleep quality were significantly more frequent in GERD (65% and 60%) but not BE (52% and 46%) compared with controls (48% and 39%). Controlling for age, race, gender, smoking, body mass index, and hypertension, the risk of poor sleep quality was significantly increased in GERD compared with controls (odds ratio [OR] = 2.79, 95% confidence interval [CI]: 1.08-6.80), significance was lost after adding OSA to the model (OR = 2.27, 95% CI: 0.87-5.85). CONCLUSIONS & INFERENCES: GERD but not BE increases the risk of poor sleep quality. This association is not independent of OSA.

Determination of the distribution of shallow-water seagrass and drift algae communities with acoustic seafloor discrimination

The spatial distribution of seagrass and algae communities can be difficult to determine in large, shallow lagoon systems where high turbidity prevents the use of optical methods like aerial photography or satellite imagery. Further complications can arise when algae are not permanently attached to the substratum and drift with tides and currents. A study using acoustic seafloor discrimination was conducted in the Indian River Lagoon (Florida, USA) to determine the extent of drift algae and seagrass. Acoustic surveys using the QTC View V system based on 50 and 200 kHz transducers were conducted near Sebastian Inlet. Results indicate that areas of seagrass can be identified, and are mixed with a high abundance of drift algae. Nearest-neighbor extrapolation was used to fill in spaces between survey lines and thus obtain spatially cohesive maps. These maps were then ground-truthed using data from towed video and compared using confusion matrices, The maps showed a high level of agreement (60%) with the actual distribution of algae, however some confusion existed between bare sand and algae as well as seagrass

Assessing the accuracy of acoustic seabed classification for mapping coral reef environments in South Florida (Broward County, USA)

The Atlantic coast of Broward County, Florida (USA) is paralleled by a series of progressively deeper, shore-parallel coral reef communities. Two of these reef systems are drowned early Holocene coral reefs of 5 ky and 7 ky uncorrected radiocarbon age. Despite the case of access to these reefs, and their major contribution to the local economy, accurate benthic habitat maps of the area are not available. Ecological studies have shown that different benthic communities (i.e. communities composed of different biological taxa) exist along several spatial gradients on all reefs. Since these studies are limited by time and spatial extent, acoustic surveys with the QTCView V bottom classification system based on a 50 kHz transducer were used as an alternative method of producing habitat maps. From the acoustic data of a 3.1 km(2) survey area, spatial prediction maps were created for the area. These were compared with habitat maps interpreted from in situ data and Laser Airborne Depth Sounder (LADS) bathymetry, in order to ground-truth the remotely sensed data. An error matrix was used to quantitatively determine the accuracy of the acoustically derived spatial prediction model against the maps derived from the in situ and LADS data sets. Confusion analysis of 100 random points showed that the system was able to distinguish areas of reef from areas of rubble and sand with an overall accuracy of 61%. When asked to detect more subtle spatial differences, for example, those between distinct reef communities, the classification was only about 40% accurate. We discuss to what degree a synthesis of acoustic and in situ techniques can provide accurate habitat maps in coral reef environments, and conclude that acoustic methods were able to reflect the spatial extent and composition of at least three different biological communities.

Effects of HZE particle on the nigrostriatal dopaminergic system in a future Mars mission.

Because of long duration travel outside the Earth's magnetic field, the effect of iron-rich high charge and energy (HZE) particles in Galactic Cosmic Rays on human body is the major concern in radiation protection. Recently attention has been directed to effects on the central nervous system in addition to mutagenic effects. In particular, a reduction in striatal dopamine content on nigrostriatal dopaminergic system has been reported by investigators using accelerated iron ions in ground-based mammalian studies. In addition, studies of the pathophysiology of Parkinson's disease demonstrated that excess iron cause a reduction in the dopamine content in the substantia nigra. This suggests an intriguing possibility to explain the selective detrimental effects of HZE particles on the dopaminergic system. Should these particles have biochemical effects, possible options for countermeasures are: (1) nutritional prevention, (2) medication, and (3) surgical placement of a stimulator electrode at a specific anatomic site in the basal ganglia.

Determination of the distribution of shallow-water seagrass and drift algae communities with acoustic seafloor discrimination.

The spatial distribution of seagrass and algae communities can be difficult to determine in large, shallow lagoon systems where high turbidity prevents the use of optical methods like aerial photography or satellite imagery. Further complications can arise when algae are not permanently attached to the substratum and drift with tides and currents. A study using acoustic seafloor discrimination was conducted in the Indian River Lagoon (Florida, USA) to determine the extent of drift algae and seagrass. Acoustic surveys using the QTC View V system based on 50 and 200 kHz transducers were conducted near Sebastian Inlet. Results indicate that areas of seagrass can be identified, and are mixed with a high abundance of drift algae. Nearest-neighbor extrapolation was used to fill in spaces between survey lines and thus obtain spatially cohesive maps. These maps were then ground-truthed using data from towed video and compared using confusion matrices, The maps showed a high level of agreement (60%) with the actual distribution of algae, however some confusion existed between bare sand and algae as well as seagrass.

Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53 status, tumor angiogenesis, and survival in platinum-treated patients.

OBJECTIVE: The regulation of the metastatic process in epithelial ovarian cancer has not been well defined. Similar to other tumor types, the angiogenic phenotype in ovarian cancer strongly influences clinical outcome, suggesting that the acquisition of a pro-angiogenic environment is essential to the process of ovarian cancer proliferation and metastasis. Thrombospondin-1 (TSP-1) is a potent peptide shown in other tumor systems to be associated with angiogenesis and possibly regulated by p53, a gene which is mutated in as high as 50% of advanced ovarian cancers. The purpose of this study was to investigate TSP-1 expression in invasive epithelial ovarian cancer and to examine the relationship between TSP-1 expression and the degree of angiogenesis. In addition, we examined whether TSP-1 expression was associated with overexpression of p53. METHODS: Frozen sections obtained from 85 patients with invasive epithelial ovarian cancer were examined immunohistochemically for expression of TSP-1 and p53. The sections were examined microscopically by two investigators, who were blinded to the clinicopathologic variables. Outcome variables included the correlation among TSP-1, angiogenesis, and p53, as well as the association between TSP-1 expression and survival. RESULTS: The majority (62%) of cases demonstrated high levels (3+) of TSP-1 expression; 7% demonstrated no TSP-1 expression. p53 was overexpressed in 55% of cases, and expression was inversely correlated with TSP-1 staining. Thirteen cancers had 0 or 1+ TSP-1 staining; 12 (92%) of these overexpressed the p53 protein. In contrast, only 49% of tumors with high expression of TSP-1 have overexpression of p53 (P = 0.02). TSP-1 was suggestive for improved survival in patients with advanced disease; high TSP-1 expression was associated with a median survival of 2.4 years compared to 1.5 years for patients with tumors having a lower degree of TSP-1 expression (P = 0.06). CONCLUSION: These data suggest that TSP-1 may possess a tumor inhibitory function in patients with advanced epithelial ovarian carcinoma. The reduction of TSP-1 expression associated with overexpression of p53 may be coupled with the development of a pro-angiogenic environment and malignant phenotype.

Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine.

The treatment of older patients with acute myeloid leukemia (AML) remains unsatisfactory, with complete remission (CR) achieved in only approximately 50% and long-term disease-free survival in 10% to 20%. Three hundred eighty-eight patients (60 years of age and older) with newly diagnosed de novo AML were randomly assigned to receive placebo (P) or granulocyte-macrophage colony-stimulating factor (GM-CSF) or GM in a double-blind manner, beginning 1 day after the completion of 3 days of daunorubicin and 7 days of cytarabine therapy. No differences were found in the rates of leukemic regrowth, CR, or infectious complications in either arm. Of 205 patients who achieved CR, 169 were medically well and were randomized to receive cytarabine alone or a combination of cytarabine and mitoxantrone. With a median follow-up of 7.7 years, the median disease-free survival times were 11 months and 10 months for those randomized to cytarabine or cytarabine/mitoxantrone, respectively. Rates of relapse, excluding deaths in CR, were 77% for cytarabine and 82% for cytarabine/mitoxantrone. Induction randomization had no effect on leukemic relapse rate or remission duration in either postremission arm. Because cytarabine/mitoxantrone was more toxic and no more effective than cytarabine, it was concluded that this higher-dose therapy had no benefit in the postremission management of older patients with de novo AML. These results suggest the need to develop novel therapeutic strategies for these patients. (Blood. 2001;98:548-553)

Acute urinary toxicity following transperineal prostate brachytherapy using a modified Quimby loading method.

PURPOSE: To examine the acute urinary toxicity following transperineal prostate implant using a modified Quimby loading method with regard to time course, severity, and factors that may be associated with a higher incidence of morbidity. METHODS AND MATERIALS: One hundred thirty-nine patients with prostate adenocarcinoma treated with brachytherapy from 1997 through 1999 had follow-up records available for review. Patients considered for definitive brachytherapy alone included those with prostate specific antigen (PSA) < or = 6, Gleason score (GS) < or = 6, clinical stage < T2b, and prostate volumes generally less than 40 cc. Patients with larger prostate volumes were given neoadjuvant antiandrogen therapy. Those with GS > 6, PSA > 6, or Stage > T2a were treated with external beam radiation therapy followed by brachytherapy boost. Sources were loaded according to a modified Quimby method. At each follow-up, toxicity was graded based on a modified RTOG urinary toxicity scale. RESULTS: Acute urinary toxicity occurred in 88%. Grade I toxicity was reported in 23%, grade II in 45%, and grade III in 20%, with 14% requiring prolonged (greater than 1 week) intermittent or indwelling catheterization. Overall median duration of symptoms was 12 months. There was no difference in duration of symptoms between patients treated with I-125 or Pd-103 sources (p = 0.71). After adjusting for GS and PSA, multivariate logistic regression analysis showed higher incidence of grade 3 toxicity in patients with larger prostate volumes (p = 0.002), and those with more seeds implanted (p < 0.001). Higher incidence of prolonged catheterization was found in patients receiving brachytherapy alone (p = 0.01), with larger prostate volumes (p = 0.01), and those with more seeds implanted (p < 0.001). CONCLUSION: Interstitial brachytherapy for prostate cancer leads to a high incidence of acute urinary toxicity, most of which is mild to moderate in severity. A prolonged need for catheterization can occur in some patients. Patients receiving brachytherapy alone, those with prostate volumes greater than 30 cc, and those implanted with a greater number of seeds have the highest incidence of significant toxicity.

High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361).

Multiparameter flow cytometry (MFC) has the potential to allow for sensitive and specific monitoring of residual disease (RD) in acute myeloid leukemia (AML). The use of MFC for RD monitoring assumes that AML cells identified by their immunophenotype at diagnosis can be detected during remission and at relapse. AML cells from 136 patients were immunophenotyped by MFC at diagnosis and at first relapse using 9 panels of 3 monoclonal antibodies. Immunophenotype changes occurred in 124 patients (91%); they consisted of gains or losses of discrete leukemia cell populations resolved by MFC (42 patients) and gains or losses of antigens on leukemia cell populations present at both time points (108 patients). Antigen expression defining unusual phenotypes changed frequently: CD13, CD33, and CD34, absent at diagnosis in 3, 33, and 47 cases, respectively, were gained at relapse in 2 (67%), 15 (45%), and 17 (36%); CD56, CD19, and CD14, present at diagnosis in 5, 16, and 20 cases, were lost at relapse in 2 (40%), 6 (38%), and 8 (40%). Leukemia cell gates created in pretreatment samples using each 3-antibody panel allowed identification of relapse AML cells in only 68% to 91% of cases, but use of 8 3-antibody panels, which included antibodies to a total of 16 antigens, allowed identification of relapse AML cells in all cases. Thus, the immunophenotype of AML cells is markedly unstable; nevertheless, despite this instability, MFC has the potential to identify RD in AML if multiple antibody panels are used at all time points. (Blood. 2001;97:3574-3580)

Significance of lymphoglandular bodies in bone marrow aspiration smears.

The presence of lymphoglandular bodies (LGB) or Söderström bodies is often stated to be a feature of lymphoid processes. In our experience, LGB are typically identified in B-cell processes but not in T-cell lymphomas or myeloid leukemias. We reviewed 136 bone marrow aspirate smears. The number of LGB per five high-power fields was counted, and median counts for B-cell processes, non-B-cell processes, myeloid leukemias, and T-cell malignancies were obtained and compared by the Wilcoxon rank sum test. Bone marrow aspirate smears involved with B-cell malignancies contained a median of 30 (range, 1-250) LGB per five high-power fields. Compared to myeloid leukemias (median, 11; range, 1-253) and T-cell malignancies (median, 7; range, 0-41), the differences were statistically significant (P < 0.001 and P = 0.01, respectively). While lymphoglandular bodies can be seen in a variety of malignant hematopoietic and nonhematopoietic disorders, they are found in significantly greater numbers in B-cell malignancies.

Pneumatic compression versus low molecular weight heparin in gynecologic oncology surgery: a randomized trial.

OBJECTIVE: To compare the efficacy and treatment-related complications of low molecular weight heparin and external pneumatic compression in the prevention of venous thromboembolism of postoperative gynecologic oncology patients. METHODS: A total of 211 patients over age 40 years, undergoing a major operative procedure for gynecologic malignancy, were randomized to receive perioperative thromboembolism prophylaxis with either low molecular weight heparin (n = 105) or external pneumatic compression (n = 106). Demographic data and clinical outcome were recorded for each patient. All patients underwent bilateral Doppler ultrasound of the lower extremities on postoperative days 3-5 to evaluate for the presence of occult deep vein thrombosis. A follow-up interview 30 days after surgery sought to detect patients who developed deep vein thrombosis or pulmonary embolism after hospital discharge. RESULTS: Venous thrombosis was diagnosed in two patients receiving low molecular weight heparin and in one patient receiving external pneumatic compression. The frequency of bleeding complications, measured by the number of required perioperative transfusions, and estimated intraoperative blood loss was similar between the two groups. CONCLUSION: Low molecular weight heparin and external pneumatic compression are similarly effective in the postoperative prophylaxis of thromboembolism. The use of low molecular weight heparin is not associated with an increased risk of bleeding complications when compared with external pneumatic compression. We believe that both modalities are reasonable choices for prophylaxis in this high-risk group of patients.