Belimumab alters transitional B-cell subset proportions in patients with stable systemic lupus erythematosus.

OBJECTIVE: We evaluated the effects of the B-cell activating factor (BAFF)-targeting antibody Belimumab on human nonmemory B-cell pools. Human B-cell pools were identified using surface markers adapted from mouse studies that specifically assessed reductions in immature B cells due to BAFF depletion. Patients with systemic lupus erythematosus (SLE) have high levels of both BAFF and immature B cells. Mechanistic mouse studies provide a framework for understanding human responses to therapies that target B cells. METHODS: Peripheral blood mononuclear cells were isolated from healthy donors and SLE patients on Belimumab or standard-of-care therapy (SCT). Cells were stained for flow cytometry to identify B-cell subsets based on CD21/CD24. Differences in subset proportions were determined by one-way ANOVA and Tukey's post hoc test. RESULTS: Patients treated with Belimumab show alterations in the nonmemory B-cell pool characterized by a decrease in the Transitional 2 (T2) subset (p = 0.002), and an increase in the proportion of Transitional 1 (T1) cells (p = 0.005) as compared with healthy donors and SCT patients. The naïve B-cell compartment showed no significant differences between the groups (p = 0.293). CONCLUSION: Using a translational approach, we show that Belimumab-mediated BAFF depletion reduces the T2 subset in patients, similar to observations in mouse models with BAFF depletion.

A spatial and temporal analysis of paediatric central nervous system infections from 2005 to 2015 in Ho Chi Minh City, Vietnam.

Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.

Exome sequencing detection of two untranslated GFPT1 mutations in a family with limb-girdle myasthenia.

The term 'limb-girdle myasthenia' (LGM) was first used to describe three siblings with proximal limb weakness without oculobulbar involvement, but with EMG decrement and responsiveness to anticholinesterase medication. We report here that exome sequencing in the proband of this family revealed several sequence variations in genes linked to proximal limb weakness. However, the only mutations that cosegregated with disease were an intronic IVS7-8A>G mutation and the previously reported 3'-UTR c.*22C>A mutation in GFPT1, a gene linked to LGM. A minigene assay showed that IVS7-8A>G activates an alternative splice acceptor that results in retention of the last seven nucleotides of intron 7 and a frameshift leading to a termination codon 13 nucleotides downstream from the new splice site. An anconeus muscle biopsy revealed mild reduction of the axon terminal size and postsynaptic fold simplification. The amplitudes of miniature endplate potentials and quantal release were also diminished. The DNA of the mildly affected father of the proband showed only the intronic mutation along with sequence variations in other genes potentially relevant to LGM. Thus, this study performed in the family originally described with LGM showed two GFPT1 untranslated mutations, which may cause disease by reducing GFPT1 expression and ultimately impairing protein glycosylation.

Impact of floor covering on wheelchair rugby players: analysis of rolling performance.

Introduction: Despite the increased interest in indoor wheelchair sports in many countries, research on the effect of floor coverings on sports performance is limited. Currently, there are no specific guidelines for covering characteristics for wheelchair sports, whether for competitive or recreational purposes. This study aimed to determine the impact of floor coverings on the biomechanical parameters of manual wheelchair propulsion for wheelchair rugby practice. Methods: Ten wheelchair rugby players performed 6 maximum-velocity sprints over 20 meters, with a 20-second recovery time between sprints, on 3 different coverings, using their personal sports wheelchairs. The coverings were: wood parquet, Gerflor TX System Endurance®, and a plastic synthetic covering (balatum). Performance and propulsion technique variables were collected using inertial measurement units (265 Hz, Kinvent, France). Additionally, rolling resistance quantification tests were conducted on each covering. Results: Rolling resistance was lowest on the wood parquet, with an average value of 3.98 ± 0.97 N. Best sprint performance was achieved on the wood parquet. The fatigue index on the parquet was significantly lower than on the balatum (p < 0.05). Discussion: Our results highlight that floor surface influences both performance and propulsion technique variables. Therefore, we recommend performing wheelchair rugby training on wood parquet to optimize performance. It is also important to consider the impact of different coverings on sprint performance when organizing player rotations to maintain a high level of competition during tournaments.

Rescue stenting after the failure of intravenous thrombolysis and bridging thrombolysis: an initial Vietnamese report.

OBJECTIVE: Intravenous (IV) recombinant tissue plasminogen activator is the standard of care for patients with acute ischemic stroke (AIS) who present to the hospital within 4.5 hours of symptom onset. However, IV thrombolysis, even bridging thrombolysis (combining intravenous thrombolysis and mechanical thrombectomy) has limited efficacy among patients who had occlusive lesions associated with high-grade arterial stenosis requiring revascularization to improve neurological deficits. We evaluated whether rescue stenting results in good outcomes among patients after the failure of intravenous thrombolysis and bridging thrombolysis. PATIENTS AND METHODS: We retrospectively analyzed patients with AIS who underwent rescue stenting for large vessel occlusion with severe atherosclerotic stenosis between May 2020 and August 2022 at Can Tho S.I.S General Hospital. Primary outcomes included the incidence of hemorrhagic transformation and the rate of good outcomes (modified Rankin Scale < 3) at 3-month follow-up. RESULTS: We identified 13 patients who received rescue stenting after the failure of IV alteplase and bridging thrombolysis, but only 11 patients met the inclusion criteria. All patients experienced successful recanalization, and 1 (9.1%) patient experienced new infarcts. Of these 11 patients, 10 (90.9%) had good outcomes 3 months after rescue stenting. Additionally, a loading dose of dual antiplatelet therapy (DAPT) applied concurrently with IV alteplase improved the recanalization rate for large target arteries but had no significant effect on the incidence of symptomatic intracranial hemorrhage. CONCLUSIONS: Rescue stenting appears to represent an additional therapeutic option in cases that fail to resolve with IV alteplase, which may improve clinical outcomes.

Rescue intracranial stenting in acute ischemic stroke: a preliminary Vietnamese study.

OBJECTIVE: In cases of acute ischemic stroke (AIS) caused by intracranial large vessel occlusion, rescue intracranial stenting (RIS) has recently emerged as a treatment option for achieving recanalization when mechanical thrombectomy (MT) fails. However, few studies to date have reported on the beneficial outcomes of RIS. Our goal was to analyze whether RIS use can improve prognosis in patients 3 months post-treatment. PATIENTS AND METHODS: A retrospective analysis was performed on a prospective cohort of patients with AIS treated with RIS at Can Tho S.I.S General Hospital. The study inclusion criteria were evidence of intracranial large vessel occlusion, absence of intracranial hemorrhage (ICH), and severe stenosis or reocclusion after MT. Patients with tandem occlusions, failure to follow up after discharge, or severe or fatal illness concomitant with AIS were excluded from the study. The primary outcome was the "non-poor" prognosis status rate at 3 months after RIS and post-procedural symptomatic ICH (sICH). RESULTS: The post-treatment outcomes of 85 eligible patients who received RIS between August 2019 and May 2021 were assessed. Of the 85 included patients, 82 (96.5%) achieved successful recanalization, and 4 (4.7%) experienced sICH. At 3-months post-treatment, 47 (55.3%) patients had "non-poor" outcomes, whereas 35 (41.2%) had good outcomes. The use of dual antiplatelet therapy was associated with new infarcts (relative risk [RR]: 0.1; 95% confidence interval [CI]: 0.01-0.7) and sICH occurrence (RR: 0.1; 95% CI: 0.01-0.9). CONCLUSIONS: Our study suggests that despite the occurrence of post-procedural sICH in a small proportion of cases, RIS could serve as a useful alternative or additional treatment in the event of MT failure.

Reproducibility of in vivo corneal confocal microscopy as a novel screening test for early diabetic sensorimotor polyneuropathy.

AIM: With the goal of identifying a valid biomarker of early diabetic sensorimotor polyneuropathy, we aimed to identify the most reliable in vivo corneal confocal microscopy (CCM) parameter for detection of abnormality of small nerve fibre morphology. METHODS: Cross-sectional examination of 46 subjects (26 with Type 1 diabetes and 20 healthy volunteers) examined by corneal confocal microscopy for intra- and interobserver reproducibility by the intraclass correlation coefficient method. Corneal nerve fibre density, nerve branch density, nerve fibre length and tortuosity were measured on the same day that subjects underwent clinical and electrophysiological examination. RESULTS: The 26 subjects with Type 1 diabetes had mean age and diabetes duration 42.8 ± 16.9 and 22.7 ± 16.4 years, respectively. Twelve of those subjects (46%) did not meet criteria for diabetic sensorimotor polyneuropathy, while five (19%) had mild, three (12%) had moderate and six (23%) had severe diabetic sensorimotor polyneuropathy. None of the healthy volunteers (mean age 41.4 ± 17.3 years) had polyneuropathy. Re-examination of selected corneal confocal microscopy images or sets of 40 images yielded very good to excellent intraclass correlation coefficients for all parameters. However, only one parameter (corneal nerve fibre length) emerged with consistently very good reproducibility using a clinically relevant 'study-level' protocol of subject re-examination (intra-observer intraclass correlation coefficient 0.72; interobserver intraclass correlation coefficient 0.73). Despite no differences in intraclass correlation coefficient between subgroups, corneal nerve fibre length was significantly lower (14.76 vs. 16.15 mm/mm(2), P = 0.04) in those with diabetes. CONCLUSIONS: Development of corneal confocal microscopy may need to focus on the measurement of corneal nerve fibre length, as it appears to have superior reliability in comparison with other parameters, and as evidence exists for its potential as a clinical biomarker of early diabetic sensorimotor polyneuropathy.

Prognosis value of revised Baux score among burn patients in developing country.

The aims of this study was to determine prognosis value of revised Baux score for burn patients in developing country. A retrospective study was conducted on all burn hospitalized patients at National Burn Hospital, Hanoi, Viet Nam during a period from 01/1/2015 to 31/12/2019. Collected criteria included age, burn extent, inhalation injury, death or survive, Baux and revised Baux score of each patients. AUC and SMR was compared between two scores. Prognosis value of revised Baux score was also classified according to age groups. The results showed that AUC of revided Baux score was significantly higher than that of Baux score (0.96 vs. 0.95; p=0.001). SMR of revised Baux score was closer to 1 than that of Baux score (1.03 vs. 1.14 respectively). For revised Baux score, AUC was highest in adult patients (0.98±0.01) followed by elderly and pediatric patients. In addition, SMR was 0.99 in adult group, 0.77 in elderly patient and was 4.36 in pediatric patients. In conclusion, the revised Baux score is more accurate than the Baux score but should only be recommended to apply in prognosis for adult and elderly burn patients in developing country.

Patients with thrombolysed stroke in Vietnam have an excellent outcome: results from the Vietnam Thrombolysis Registry.

BACKGROUND AND PURPOSE: We present the early experience in thrombolysis in three major centers of Ho Chi Minh city, namely 115 People Hospital, Gia Dinh Hospital, and An Binh Hospital. METHODS: A prospective study of consecutive patients treated with intravenous tPA with a treatment protocol similar to that of the National Institute of Neurological Disorders and Stroke (NINDS) trial. National Institutes of Health Stroke Scale (NIHSS) scores on admission and Modified Rankin Scale (MRS) scores at 3 months were measured for all patients. Intracranial and systemic hemorrhagic complications were recorded. RESULT: A total of 121 of 6171 (2%) patients with acute IS received thrombolysis over 3 years. Mean age was 57 years (range 18-78) and initial median NIHSS score was 12 (range 5-23). The mean delay between symptom onset and treatment was 143 min (range 50-210). Seventy-three (60.3%) patients received the standard dose with the remaining 48 patients (36.9%) treated with a lower dose, a mean calculated dose of 0.62 mg/kg (range, 0.6-0.86 mg/kg). Over half (56.3%) of the patients receiving low dose achieved functional independence (mRS score 0-1) at 3 months compared with 34.2% in the standard-dose group (P = 0.01). The 3-month mortality rate was also higher in the standard-dose group (2.1% vs. 12.5% with standard-dose tPA; P = 0.04). Symptomatic intracranial hemorrhage was noted in four patients of standard-dose group and one patient of low-dose group (P = 0.36). CONCLUSION: Intravenous thrombolysis, particularly in a lower dose, is safe and feasible in the treatment of acute IS in our selected Vietnamese population.

Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model.

BACKGROUND: Fragile X syndrome (FXS) is the most common single gene inherited form of mental retardation, with behaviours at the extreme of the autistic spectrum. Subjects with FXS and fragile X mental retardation gene knock out (Fmr1 KO) mice, an animal model for FXS, have been shown to exhibit defects in dendritic spine maturation that may underlie cognitive and behavioural abnormalities in FXS. Minocycline is a tetracycline analogue that has been used in clinical trials for stroke, multiple sclerosis and several neurodegenerative conditions. METHODS: We evaluated the effects of minocycline on dendritic spine development in the hippocampus of young Fmr1 KO mice, and in primary cultures of hippocampal neurons isolated from those mice. Cognitive effects of minocycline in young WT and Fmr1 KO mice were also evaluated using established behavioural tests for general cognition, activity and anxiety. RESULTS: Our studies demonstrate that minocycline promotes dendritic spine maturation both in cultures and in vivo. The beneficial effects of minocycline on dendritic spine morphology are also accompanied by changes in the behavioural performance of 3-week-old Fmr1 KO mice. Minocycline treated Fmr1 KO mice show less anxiety in the elevated plus maze and more strategic exploratory behaviour in the Y maze as compared to untreated Fmr1 KO mice. Our data suggest that these effects of minocycline may relate to its inhibitory action on MMP-9 expression and activity, which are higher in the hippocampus of Fmr1 KO mice. CONCLUSION: These findings establish minocycline as a promising therapeutic for the treatment of fragile X mental retardation.

Brachial plexopathy complicating Epstein-Barr virus infection in an adult.

Acute Epstein-Barr virus (EBV) infection is associated with central and peripheral neurological complications such as meningitis, encephalitis, myelitis and radiculopathy in 0.5-7.5% of patients. The peripheral nervous system manifestations of acute EBV infection include mononeuropathy, mononeuritis multiplex, autonomic neuropathy, and polyradiculopathy. Brachial plexopathy in children and immunocompromised adults with acute EBV infection has been described, likely as a dysimmune neuropathy triggered by the EBV. We present a case of brachial plexopathy complicating prior EBV infection in a healthy adult.

Profile and outcome of burn injuries amongst preschool children in a developing country.

The aim of this study was to investigate characteristics, outcomes and risk factors for death from burn in preschool children. A retrospective study was conducted on 3688 preschool burn children admitted to the National Burn Hospital from 1/1/2016 to 31/12/2018. Collected data included patient demographics and burn characteristics. Bivariate and multivariate analysis was conducted to determine independent risk factors for death. Results showed that preschool children accounted for 78.8% of total admitted burn children. The main causal agent was scald. Boys were predominant, and 76.5% patients lived in rural areas. The highest number of burn accidents occurred in winter. In addition, average burn surface area was of 8.8% total body surface area (TBSA) and 43.5% of patients suffered deep burn injury. Overall mortality rate was 0.5% with LA50 of 81.7% and 49.1% for full thickness burn area. A significantly higher mortality rate was seen in patients with inhalation injury. Compared to survivors, patients who died had a significantly larger burn surface area and larger deep burn area. Multivariate logistic analysis for death indicated that presence of inhalation injury and increased burn extent were independent risk factors for death. Inhalation injury resulted in a 3.4 probability unit of death. In conclusion, preschool burn injuries were more common in boys living in the countryside and were mostly caused by scald, with a high proportion of deep injuries. Except for in cases of extensive burn, inhalation injury was not common but was still the main cause of death.

Le but de ce travail rétrospectif réalisé entre le 1/1/2016 et le 31/12/2018 sur 3 688 enfants hospitalisés dans l'hôpital brûlologique national était d'étudier les caractéristiques, l'évolution et les déterminants de mortalité (analyse multivariée) des brûlures touchant des enfants d'âge pré- scolaire. Ces enfants comptent pour 78,8% des admissions pédiatriques. L'ébouillantement est le mécanisme prédominant. Les garçons sont plus touchés ; 76,5 % des patients habitent en milieu rural et les brûlures sont plus fréquemment hivernales. La surface brûlée moyenne est de 8,8% et 43,5% des patients ont des atteintes profondes. La mortalité est de 0,5% avec une DL50 de 81,7% dont 49,1% de profond. En analyse multivariée, l'augmentation de surface brûlée et l'inhalation de fumées (OR 3,4) sont des facteurs indépendants de risque de mortalité. Les brûlures survenant à l'âge préscolaire sont donc des ébouillantements de garçons ruraux, fréquemment profonds. L'inhalation de fumées est donc rare mais reste un facteur de risque mortalité.

Identification of lipopolysaccharide binding site on high molecular weight kininogen.

Plasma kallikrein kinin system (KKS) activation along with its cellular receptors expression are increased after injury and in patients with septic shock, hypotensive bacteremia and rhesus monkey infected with Salmonella typhimurium. KKS signaling cascade is activated by activated factor XII (FXIIa, Hageman factor)- and prolylcarboxypeptidase (PRCP)-dependent pathways on endothelial cells. Among the many entities that comprise the KKS, high molecular weight kininogen (HK), a bradykinin precursor, is critical in the assembly and activation of this system. HK is primarily expressed in the liver and secreted into the bloodstream. The activation of the KKS influences the permeability of the endothelium by liberating bradykinin (BK) from HK. BK is a potent inflammatory peptide which stimulates constitutive bradykinin B2 and inducible B1 receptors to release nitric oxide and prostacyclin. Regardless of the triggers, PK can only be activated on HK bound to the artificial negatively charged or to cell membrane surfaces. Since LPS has a negatively charged moiety and the ability to induce inflammatory responses in human, we determined the interaction between LPS and HK. HKH19 (HK cell binding site) and heparin inhibited LPS binding to HK with IC(50)s of 15nM and 20 microg/ml, respectively. C1-inhibitor and N-acetylglucosamine glycan inhibited LPS binding to HK with IC(50)s of about 10 microg/ml and 10mM, respectively. This novel study underscores the implication of HK in infection. We propose that HKH19, heparin, and C1-inhibitor present therapeutic potential for the treatment of sepsis and hypotensive bacteremia.

Thrombolysis in recurrent lacunar stroke: a case example.

BACKGROUND AND PURPOSE: We report a case of intravenous thrombolysis in a patient with early recurrent stroke. A 62-year-old man recovered nearly completely after a lacunar infarct of the left putamen. He suffered stroke recurrence 7 days later due to a new infarct in the left internal capsule. Intravenous alteplase 0.9 mg/kg was administered 40 min after the symptom onset resulting in significant neurologic improvement. CONCLUSION: Intravenous thrombolysis may be safe for early recurrent lacunar stroke in patients with relatively small risk of hemorrhage.

[Bronchial involvement in an immunocompetent adult with varicella pneumonia]. / Atteinte bronchique au cours d'une pneumonie varicelleuse chez un adulte immunocompétent.

INTRODUCTION: Pneumonitis caused by varicella infection is a serious and potentially life-threatening complication of the disease when it occurs in adults. The incidence of this complication has increased in the last 10 years. OBSERVATION: We report the case of a non-immunocompromised patient admitted to hospital because of varicella pneumonia not requiring intensive care. Bronchoscopy revealed vesicular lesions on the bronchial mucosa. The patient made a full recovery with anti-viral therapy. CONCLUSION: Vesicular lesions can be observed on the bronchial mucosa of adult patients with varicella zoster infection.

A pilot study to compare the use of the Excorim staphylococcal protein immunoadsorption system and IVIG in chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune mediated neuropathy responding to immunomodulation with IVIG or plasma exchange (PE). We tested the efficacy and safety of selective immunoglobulin removal by Excorim immunoadsorption (IA) in a pilot trial in CIDP patients randomized to monthly IA or IVIG treatments for 6 months. Response rates at 2 and 6 months were greater with IA due to longer disease duration and greater disability at baseline in the patients receiving IVIG. IA appears to be a safe and efficacious therapy for patients with CIDP, but an appropriately powered clinical trial with stratification for disease duration is required.

Comparison of a neurothesiometer and vibration in measuring vibration perception thresholds and relationship to nerve conduction studies.

OBJECTIVE: To compare vibration perception thresholds (VPTs) obtained with two different instruments, a neurothesiometer and a vibratron, and to characterize variability of repeat measures and correlation with sural nerve conduction parameters. RESEARCH DESIGN AND METHODS: A total of 152 patients with diabetic peripheral neuropathy received electrodiagnostic evaluation and quantitative VPT testing with the Vibratron II and the Horwell Neurothesiometer. Of the patients, 42 returned for repeat nerve conduction studies and VPT testing with both types of equipment on three separate occasions. RESULTS: The variability of repeat testing for the vibratron was 34 and 31% in the right and left first toes, respectively. Variability for neurothesiometer was 8 and 6% for the right and left toes. This variability compares with that of sural nerve conduction velocity of 2% and that of sural nerve amplitude of 8% in this series of patients. CONCLUSIONS: We conclude that VPT determined with the neurothesiometer is less variable than with the vibratron and more reflective of peripheral nerve function. Our results indicate that the neurothesiometer can be used reliably in clinical research trials.

Differential expression of transforming growth factor-beta receptors in a rabbit zone II flexor tendon wound healing model.

Flexor tendon repair in zone II is complicated by adhesions that impair normal postoperative gliding. Transforming growth factor-beta (TGF-beta) is a family of growth factors that has been implicated in scar formation. The TGF-beta family of proteins binds to three distinct classes of membrane receptors, termed RI, RII, and RIII. In this study, we analyzed the temporal and spatial distribution of TGF-beta receptor isoforms (RI, RII, and RIII) in a rabbit zone II flexor tendon wound healing model.Twenty-eight adult New Zealand White rabbit forepaws underwent isolation of the middle digit flexor digitorum profundus tendon in zone II. The tendons underwent transection in zone II and immediate repair. The tendons were harvested at increasing time points: 1, 3, 7, 14, 28, and 56 days postoperatively (n = 4 at each time point). The control flexor tendons were harvested without transection and repair (n = 4). Immunohistochemical analysis was used to detect the expression patterns for TGF-beta receptors RI, RII, and RIII. Immunohistochemical staining of the transected and repaired tendons demonstrated up-regulation of TGF-beta RI, RII, and RIII protein levels. TGF-beta receptor production in the experimental group (transection and repair) was concentrated in the epitenon and along the repair site. Furthermore, the TGF-beta receptor expression levels peaked at day 14 and decreased by day 56 postoperatively. In contrast, minimal receptor expression was observed in the untransected and unrepaired control tendons. These data provide evidence that (1) TGF-beta receptors are up-regulated after injury and repair; (2) peak levels of TGF-beta receptor expression occurred at day 14 and decreased by day 56 after wounding and repair; and (3) both the tendon sheath and epitenon have the highest receptor expression, and both may play critical roles in flexor tendon wound healing. Understanding the up-regulation of TGF-beta isoforms and the up-regulation of their corresponding receptors during flexor tendon wound healing provides new targets for biomolecular modulation of postoperative scar formation.

Smoking and obesity are associated with the progression of aortic stenosis.

OBJECTIVE: The purpose of the study was to identify clinical predictors of progression of aortic stenosis. BACKGROUND: The natural history of valvular aortic stenosis includes a latency period followed by an unpredictable progression. Recent investigations have shown an association between risk factors for atherosclerosis and the presence of aortic stenosis. The authors hypothesized that atherosclerosis risk factors are also associated with the progression of aortic stenosis. METHODS: In a retrospective study, patients with a diagnosis of aortic stenosis were identified by continuous wave Doppler and a follow-up study of at least 6 months. Clinical data at the time of the index echocardiogram were obtained from review of patients' medical records. Independent risk factors for the progression of aortic stenosis were identified by stepwise logistic regression analysis. RESULTS: One hundred twenty-three patients were identified, and complete data were obtained for 87 patients (mean age, 70.7 +/- 10 years; men, 81%; mean follow-up, 2.54 +/- 1.6 years). The initial gradient was mild in 61% of patients and moderate in 31%. The mean rate of progression was 6.3 +/- 13 mm Hg/year. Mild aortic stenosis in 36% of patients at the time of the index echocardiogram progressed to moderate or severe over an average of 2.9 +/- 2.0 years. Independent clinical factors associated with a progression of 5 mm Hg/year or greater included a history of smoking (relative risk [RR] = 3.06; 95% confidence interval [CI] = 1.09-8.61; p = 0.034) and body mass index (RR = 1.16; 95% CI = 1.03-1.30; p = 0.013). Hypertension, diabetes, cholesterol, age, gender, and coronary artery disease were not independently associated with progression. CONCLUSIONS: Body mass index and a history of smoking are independent predictors of significant progression of aortic stenosis, defined as > 5 mm Hg/year. The rate of progression of aortic stenosis is variable. However, a substantial number of patients have progression of even initially mild aortic stenosis within a relatively short period of time. The effect of controlling atherosclerosis risk factors on the rate of progression of aortic stenosis remains to be determined.