Course Of Adult Patients Research Articles

Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH

AbstractFamilial hemophagocytic lymphohistiocytosis (HLH) is a rare primary immunodeficiency disorder characterized by defects in cell-mediated cytotoxicity that results in fever, hepatosplenomegaly, and cytopenias. Familial HLH is well recognized in children but rarely diagnosed in adults. We conducted a retrospective review of genetic and immunologic test results in patients who developed HLH in adulthood. Included in our study were 1531 patients with a clinical diagnosis of HLH; 175 patients were 18 years or older. Missense and splice-site sequence variants in PRF1, MUNC13-4, and STXBP2 were found in 25 (14%) of the adult patients. The A91V-PRF1 genotype was found in 12 of these patients (48%). The preponderance of hypomorphic mutations in familial HLH–causing genes correlates with the later-onset clinical symptoms and the more indolent course in adult patients. We conclude that late-onset familial HLH occurs more commonly than was suspected previously.

Glomerular Density-Associated Changes in Clinicopathological Features of Minimal Change Nephrotic Syndrome in Adults

Background: Differences in nephron number and/or glomerular size between individuals, in relation to intrauterine growth retardation or low birth weight, have been suggested to affect the clinical course of minimal change nephrotic syndrome (MCNS) in children. However, no previous study has investigated the potential influences of these histological variables on the clinical course of adult patients with MCNS. Methods: The glomerular density (GD; the number of non-sclerotic glomeruli per renal cortical area) and the glomerular volume (GV) were evaluated using renal biopsy specimens from adult patients with a histological diagnosis of MCNS (n = 50). Relationships between these variables and clinicopathological features, including the initial response to corticosteroid therapy, were analyzed. Results: Both the GD (1.5–6.5/mm²) and the GV (1.2–4.4 × 10⁶ µm³) showed about 4-fold variations, and a close inverse correlation was observed between these two variables. Notably, the MCNS patients with a low GD showed a trend towards having similar clinicopathological characteristics as patients with a histological diagnosis of focal segmental glomerular sclerosis, as compared to the MCNS patients with a high GD. In addition, during the initial treatment with corticosteroids, the number of patients achieving complete remission was significantly lower in the MCNS patients with a low GD than that in the MCNS patients with a high GD. Conclusion: These results suggest that the GD in renal biopsies may be an important determinant of the glomerular size variability, and can therefore influence the clinical phenotype, such as the response to corticosteroid therapy, in adult patients with MCNS.

CD11b Expression Is An Independent Adverse Prognostic Factor in Pediatric Acute Myeloid Leukemia Treated with Allogeneic Stem Cell Transplantation,

Abstract 4092 Background:The adhesion molecule CD11b, which associates with the beta2-integrin to form the Mac-1 complex, is expressed in monocytic leukemias as well as other myeloid leukemias. Its expression on the lekemic cells has been reported to correlate with more aggressive course in adult patients with AML. The clinical relevance of CD11b expression in pediatric AML is not known. More importantly, the clinical relevance of CD11b expression on pediatric AML when these patients are treated with allogeneic hematopoietic stem cell transplant (HSCT). We investigated whether HSCT can modify the expected adverse effects of CD11b expression in pediatric AML patients. Methods:Immunophenotype data of 62 pediatric patients with AML, all treated with allogeneic HSCT, was reviewed. The expression of the CD11b on the blast population as determined by flow cytometry was correlated with clinical data and outcome. The median age of patients was 8 years (range: 8 months–14 years) and included 47 (76%) patients transplanted in their first complete remission (CR1). Fourty six (74%) of all patients had intermediate-risk cytogenetics and the remaining (26%) had adverse-risk cytogenetic abnormalities. Results:Twenty five (40%) of all studied patients expressed CD11b on the surface of the blasts at diagnosis. Patients with CD11b expression had significantly shorter overall survival (P=0.038) with median survival of approximately 11 months while the median survival in the CD11b negative patients has not been reached. Similarly, CD11 positive patients had significantly shorter event free survival (EFS) (P=0.03). When we considered only patients treated with HSCT in CR1, the OS and EFS for the CD11b positive patients were both significantly shorter (P=0.04 and P=0.05, respectively). Multivariate analysis including CD11b expression and cytogenetic risk identified CD11b expression as an independent prognostic factor for survival and EFS, while cytogenetic-risk stratification became no longer a predictor. Conclusion:Our data suggests that the expression of CD11b in pediatric AML is a significant independent poor prognostic factor and HSCT does not change this trend. Most of the CD11b positive patients die in their first year after HSCT and the management of these patients should be modified to address the biological basis of this subset of AML that expresses CD11b adhesion molecule. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Clinical course of adult patients with ependymoma

Ependymomas are a rare tumor in adults, and there are limited reports of the clinical course, treatment, and current health status of patients. Patients with ependymoma completed an online survey regarding their diagnosis, treatment course, and current health status. Descriptive statistics were used to report the characteristics and degree of symptom severity. Correlations between demographic and clinical characteristics were explored with univariate analysis. One hundred eighteen adults participated, and there were more women (n = 68) than men (n = 50). The median age was 48 years (range, 22-77 years). Fifty-nine participants (48%) reported that they had not been able to work since their diagnosis, and 31% reported receiving disability benefits. Patients who had been treated for spine tumors had symptoms longer than those who had been treated for brain lesions (chi-square statistic, 7.294; P = .026), and the majority had 3 symptoms before diagnosis. Most patients reported undergoing complete resection (brain lesions, 62%; spine tumors, 58%), and patients with spine tumors were less likely to have received additional treatment (chi-square statistic, 9.687; P = .008). The majority had not had a recurrence and reported consulting a neurosurgeon for surveillance. Despite having stable disease and not receiving active treatment, most patients described moderate to severe symptoms, including fatigue (44%), numbness/tingling (39%), pain (36%), and disturbed sleep (34%) overall. Brain lesions were associated with altered vision (25%), difficulty concentrating (25%), weakness (19%), irritability (19%), difficulty speaking (19%), and understanding (17%); and spine lesions were associated with extremity weakness (55%), sexual dysfunction (48%), radiating pain (37%), and change in bowel pattern (35%). Treatment for adult patients with ependymoma is not standardized. Despite the low recurrence rate, patients reported significant symptoms and disability.

Precursor B cell lymphoblastic lymphoma presenting as a solitary bone tumor: a case report and review of the literature

Precursor B cell lymphoblastic lymphoma (B-LBL) is quite uncommon and it usually manifests as an extranodal disease. Although B-LBL may present with bone involvement, it is a very rare manifestation of B-LBL as a primary solitary bone tumor. Here, we report a case of precursor B-LBL presenting with solitary bone tumor and a review of a total of seven adult patients reported previously in the literature. We described demographic and clinical characteristics of these patients with unique presentation and discussed treatment options. Unlike previous reports except one case, our patient underwent allogeneic stem cell transplantation (allo-SCT) due to refractory disease. She is alive without evidence of disease by the post-transplant 12th month. B-LBL has an aggressive clinical course in adult patients and allo-SCT may be the best treatment option.

Serum anti-glycan antibodies predict complicated Crohnʼs disease behavior

A high proportion of patients with Crohn's disease (CD) over time develop complications like fistulae and strictures, requiring surgery. We tested a panel of antiglycan antibodies for predicting the occurrence of complications and CD-related surgery in an adult patient cohort. Serum samples of 149 CD patients of the German inflammatory bowel disease (IBD) network were tested for the presence of anti-laminarin IgA (Anti-L), anti-chitin IgA (Anti-C), anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-mannobioside IgG (AMCA), and anti-Saccaromyces cerevisiae IgG (gASCA) carbohydrate antibodies by enzyme-linked immunosorbent assay (ELISA) (IBDX(R) panel, Glycominds, Lod, Israel) in a blinded fashion. Clinical data were available on occurrence of complicated disease or CD-related surgery as well as disease activity, onset, and location. The median follow-up of the patients without any previous complication or surgery at time of sample procurement was 53.7 months. Overall, 26.3% developed a complication and 17.1% underwent CD-related surgery, respectively. Positivity for gASCA, AMCA, ACCA, and Anti-L alone or an increasing frequency of positive serum antibodies independently predicted a faster progression toward a more severe disease course. Once a complication or surgery had occurred only positivity for Anti-L or more than 3 markers out of the whole panel indicated progression to an additional surgery or complication. The antibody status of most patients remained stable over time. This is the first study showing the clinical value of serum antiglycan antibodies for prediction of a more complicated disease course in adult patients with CD.

Predictors of a Prolonged Clinical Course in Adult Patients with Herpes Simplex Virus Encephalitis

Herpes simplex virus encephalitis (HSVE) patients occasionally follow a prolonged course despite standard antiviral treatment. The purpose of this study was to analyze clinical variables to identify predictors of a prolonged course. A series of 23 HSVE patients treated with acyclovir (ACV) during the acute stage were selected and divided into 2 groups: the non-prolonged group (n = 15), with improvement within 2 weeks after initial ACV treatment; and the prolonged group (n = 8), without improvement within 2 weeks. Differences in clinical variables, including age, duration from onset to initial ACV treatment, Glasgow coma scale (GCS) score, corticosteroid administration, detection of abnormal lesions on initial cranial computed tomography (CT) and magnetic resonance imaging, detection of periodic lateralized epileptiform discharges on electroencephalogram, and clinical outcome, were compared between the groups. There were significant differences in GCS score, clinical outcome, and detection of lesions on CT between the non-prolonged and prolonged groups [p = 0.021, p = 0.041 (Mann-Whitney's U test), respectively, and p = 0.027 (Fisher's exact test)]. Four of the eight patients with a prolonged course had a poor outcome despite treatment with additional drugs. A lower GCS and a higher rate of lesions on CT were identified as predictors of a prolonged course for HSVE. These predictors are in accordance with the conventional predictors of poor outcome for HSVE. This study suggests that the initial ACV treatment was insufficient for HSVE patients with these predictors at the acute stage. The initial treatment may need to be modified for such patients.

Do pilocytic astrocytomas have a benign course in adult patients?

Do pilocytic astrocytomas have a benign course in adult patients?

Inflammatory response and clinical course of adult patients with nosocomial bloodstream infections caused by Candida spp.

Candida spp. are an important cause of nosocomial bloodstream infection (nBSI) and are associated with significant morbidity and mortality. An historical cohort study was performed to evaluate the clinical course of 60 randomly selected adult patients with nBSIs caused by Candida spp. Patients with BSI caused by Candida albicans (n = 38) and non-albicans spp. (n = 22) were compared with 80 patients with Staphylococcus aureus BSI by serial systemic inflammatory response syndrome (SIRS) and APACHE II scores. The patients had a mean age of 52 years, the length of hospital stay before BSI averaged 21 days, and 57% of patients required care in an intensive care unit before BSI. The mean APACHE II score was 17 on the day of BSI, and 63% of BSIs were caused by C. albicans. Antifungal therapy within the first 24 h of onset of BSI was appropriate in 52% of patients. Septic shock occurred in 27% of patients, and severe sepsis in an additional 8%. Overall mortality was 42%, and the 7-day mortality rate was 27%. The inflammatory response and clinical course were similar for patients with BSI caused by C. albicans and non-albicans spp. In univariate analysis, progression to septic shock was correlated with high overall mortality, as was an APACHE II score >25 at the onset of BSI. In multivariate analysis, the APACHE II score at the onset of BSI and a systemic inflammatory response independently predicted overall mortality, but the 7-day mortality rate was only predicted independently by the APACHE II score. Clinical course and mortality in patients with Candida BSI were predicted by systemic inflammatory response and APACHE II score, but not by the infecting species.

Characterization of relapses in adult idiopathic inflammatory myopathies

The objective of the current report was to determine the relapse rates and characterize the nature of relapses during the disease course of adult patients with idiopathic inflammatory myopathies (IIM). A retrospective cohort study of 53 medical records of patients with polymyositis (PM), dermatomyositis (DM), connective tissue disease (CTD)-associated myositis, and malignancy-associated myositis at an academic rheumatology center was performed. Medical records were reviewed to determine clinical presentation, initial treatment, and clinical follow-up, with an emphasis on relapses. Relapses were defined as a sustained elevation in serum creatine kinase (CK) levels in the absence of an alternative etiology. Patients were followed for an average of 65+/-43 months. All patients received corticosteroids, and 35 patients received additional immunosuppressive medications as part of their initial treatment. Serum CK levels normalized in 51 patients, and muscle strength normalized in 43 patients. Biochemical relapse was observed in 33 patients (65%). Patients with PM and CTD-associated myositis had a higher relapse rate compared to DM and malignancy-associated myositis patients. Multiple relapses were observed in 17 patients. Relapses tended to occur within the first 2 years after treatment initiation and during the tapering phase of treatment. No risk factors were unequivocally identified, although advanced age and increased duration of symptoms prior to treatment initiation had nonsignificant associations with increased risk of relapse. In conclusion, initial treatment of IIM results in a high rate of normalization of serum CK and muscle weakness. However, physicians should be aware of the high rate of relapse in patients with IIM.

Arrhythmias in patients with surgically treated atrial septal defects.

Atrial arrhythmias complicate the clinical course of adult patients with an atrial septal defect. Atrial flutter is more prevalent in younger patients, and frequently regresses after surgical defect closure. Atrial fibrillation however, which results from a chronic underlying disease, rarely reverts to sinus rhythm after surgical repair. While younger patients with atrial flutter clearly benefit from defect closure alone, this is not evident in older patients with fibrillation, who may need an additional anti-arrhythmic procedure concomitant to defect closure.

Arrhythmias in patients with surgically treated atrial septal defects.

Atrial arrhythmias complicate the clinical course of adult patients with an atrial septal defect. Atrial flutter is more prevalent in younger patients, and frequently regresses after surgical defect closure. Atrial fibrillation however, which results from a chronic underlying disease, rarely reverts to sinus rhythm after surgical repair. While younger patients with atrial flutter clearly benefit from defect closure alone, this is not evident in older patients with fibrillation, who may need an additional anti-arrhythmic procedure concomitant to defect closure.

Arrhythmia and survival in patients >18 years of age after the Mustard procedure for complete transposition of the great arteries

Increasing numbers of patients who underwent Mustard repair as children are now adults. Loss of sinus rhythm, supraventricular arrhythmias, and sudden death have been described in pediatric series. However, little is known about the clinical course of adult patients. This retrospective cohort study examined 86 consecutive adults (age >18 years) who had undergone the Mustard procedure and were referred to an adult congenital cardiac clinic for ongoing follow-up. The incidence and predictors of arrhythmia, congestive heart failure, and death were determined. The median follow-up period was 8 years after age 18 or 23 years after Mustard repair. There were 8 deaths (9%), 2 were sudden. Congestive heart failure (CHF) requiring hospital admission occurred in 9 patients (10%). Pulmonary hypertension and systemic ventricular dysfunction were independent risk factors for death or CHF. Only 29 patients (34%) remained arrhythmia-free. Forty-one patients (48%) had at least 1 episode of supraventricular tachycardia (SVT), with most patients (30, 73%) having atrial flutter. SVT after the age of 18 was associated with CHF. Pulmonary hypertension, systemic ventricular dysfunction, and junctional rhythm before age 18 were independent risk factors for SVT. Pacemakers were implanted in 19 patients (22%); 13 of those were beyond age 18. Thus, adult survivors of the Mustard procedure continue to be at risk for premature death, CHF and supraventricular tachyarrhythmia.

The Fontan Procedure in Adults

Background. A retrospective clinical study was performed to document the course of adult patients undergoing the Fontan procedure.Methods. Between 1982 and 1994, 21 adults aged 18 to 40 years (mean age, 27 ± 7 years) underwent a Fontan procedure. Anatomic diagnosis was tricuspid atresia in 9, double-inlet left ventricle in 4, and various single ventricles in 8. Four underwent a right atria–right ventricle connection, 13 had a right atria–pulmonary artery connection, and 4 had a lateral-tunnel Fontan. Three of these 4 had a snare-adjustable atrial septal defect. Preoperative risk factors assessed were left ventricular end-diastolic pressure greater than 10 mm Hg, ejection fraction lower than 0.45, mean pulmonary artery pressure higher than 15 mm Hg, transpulmonary gradient greater than 10 mm Hg, pulmonary artery abnormalities, and atrioventricular valve regurgitation. Mean preoperative risk score was 1.6 ± 1.1. Mean New York Heart Association class was 2.6 ± 0.5.Results. The operative mortality rate was 5% (1/21). Six patients (30%) had a major complication, four being prolonged effusions. One patient was lost to follow-up; the remaining 20 have been followed for a mean of 7.4 ± 3.8 years. At follow-up, mean New York Heart Association class was 1.7 ± 0.5. There has been one late death (5%) at 923 years, which was probably due to ventricular arrhythmia. Three patients (16%) have required and survived reoperation. During follow-up, 7 patients (37%) have had development of atrial arrhythmias requiring medication, and 2 have been treated for ventricular arrhythmias.Conclusions. These results indicate that properly selected adults can undergo the Fontan procedure with low morbidity and mortality. However, late-developing arrhythmias, need for reoperation, and decreasing ventricular function are serious problems that mandate careful follow-up.(Ann Thorac Surg 1997;63:1085–90)

Corrected transposition of the great arteries without associated defects in adult patients: clinical profile and follow up.

To assess the clinical course of adult patients with corrected transposition of the great arteries without associated anomalies. All patients with corrected transposition of the great arteries without associated anomalies were reviewed with complete clinical and echocardiographic assessment. The complications were evaluated in each decade. Tertiary centre with a specific unit dealing with "grown-up" adolescent and adult congenital heart disease, designated as a quaternary centre and a general hospital with a referral centre for "grown-up" congenital heart disease. 18 patients (nine male and nine female) aged 16-61 years followed for 1-30 years (mean 10 years). There were no deaths. Six patients had a worsening ability index during follow up. Complications were: (a) complete heart block in seven, three of whom required pacemaker insertion; (b) significant left atrioventricular valve regurgitation in 50%, appearing only in the third decade (12%), with increasing frequency thereafter. Infective endocarditis was responsible for increasing left atrioventricular valve regurgitation in only one patient; (c) supraventricular arrhythmia appeared in the fifth decade, and occurred in all patients over the age of 60 years. One patient aged 61 had recurrent sustained ventricular tachycardia; and (d) congestive heart failure developed only after 50 years in 66%. One patient had severe left atrioventricular valve regurgitation; the function of the systemic ventricle was only moderately reduced in the other three. Three of the nine women had seven uneventful pregnancies. Patients with corrected transposition of the great arteries without associated defects may remain undiagnosed until adult life. Symptoms occur rarely before the fourth and fifth decades, when rhythm disturbance, left atrioventricular valve regurgitation, and moderately impaired systemic ventricular function cause congestive cardiac failure. The role of pacemaker insertion or surgery for left atrioventricular valve regurgitation needs further assessment.

Long-term course of adult patients with delayed sleep phase syndrome.

A response to treatment and long-term course of 14 adults with delayed sleep phase syndrome were investigated with the use of their hospital records and mailed questionnaires. Six patients treated with chronotherapy showed full recovery just after the treatment. In three of them the delay of sleep phase relapsed one year afterwards. Four of five patients treated with pharmacotherapy alone showed partial recovery. Six of nine patients followed for periods of longer than three years after treatment showed good prognoses, though all of them still had a mild phase delay and had to shorten their sleep time in order to work full-time. The three others had poor prognoses and one of them was under psychiatric treatment for affective instability. These findings suggest that a long-term follow-up is needed to judge the effect of the treatment.

Status epilepticus at an urban public hospital in the 1980s.

We retrospectively reviewed the clinical course of adult patients treated for generalized status epilepticus (SE) at the San Francisco General Hospital (SFGH) from 1980 to 1989. The review was designed to determine whether the etiologies of SE at our hospital have changed over the last two decades, and to investigate the relationships between etiology, response to anticonvulsant therapy, and short-term clinical outcome. Of 154 patients reviewed, the four leading etiologies for SE were anticonvulsant drug withdrawal (39), alcohol-related (39), drug toxicity (14), and CNS infection (12). This pattern was essentially unchanged from observations made at SFGH in the 1970s. Sixty percent of all patients responded to first-line drug treatment (usually phenytoin +/- diazepam), and the remainder required an additional agent (usually phenobarbital) for control of SE. The best response to anticonvulsants occurred in patients with SE related to tumor, anticonvulsant drug withdrawal, or refractory epilepsy, and the poor responders had anoxia, drug toxicity, CNS infection, or other metabolic abnormalities. Seventy-six percent of the patients had good outcomes. Of the 22 patients who died, SE was a likely cause of death in only two (ie, 1.3% of the entire study group). Metabolic abnormalities, stroke, and anoxia were associated with particularly poor outcomes compared with other etiologies. These observations show that the etiologies of SE have remained similar over two successive decades, and that the etiology of SE may help predict both the initial response to drug therapy and the short-term outcome.

The clinical course of patients with severe “rheumatic” mitral insufficiency

This study has been concerned chiefly with the clinical course of adult patients with predominant rheumatic mitral insufficiency under medical management. It is based on a series of 42 patients followed medically, and a group of 115 patients who underwent cardiac surgery. These have been compared with a group of 138 patients proven to have pure mitral stenosis at surgery. The patients were similar in age and sex. Rheumatic fever had been diagnosed in more than half the patients with insufficiency, and subacute bacterial endocarditis had occurred more frequently, but a history of systemic embolism was less frequent in insufficiency than in stenosis. Strikingly different was the tendency of patients with insufficiency to develop atrial fibrillation and enlargement of the left ventricles and left atria, the latter often very marked. It has been shown that mitral insufficiency may exist in the symptom-free stage for many years, and many of these patients may be in atrial fibrillation and have large and even gigantic left atria, and left ventricular enlargement. Deterioration may be very slow, although sudden death may occur occasionally. The more malignant course and the difference in clinical profile of patients with ruptured papillary muscles or chordae tendineae is described in a group of 13 such patients. The implications of this study in connection with the selection of patients for cardiac surgery have been discussed.