Natural Course Of Patients Research Articles

Safety and Outcome after Thrombolysis in Stroke Patients with Mild Symptoms

Background: Thrombolytic therapy is frequently withheld in patients with minor stroke symptoms. However, recent studies demonstrate that a substantial proportion of these patients dies or remains permanently disabled because of underestimation of symptom severity at baseline or secondary deterioration. We aimed to assess the safety and outcome of thrombolysis therapy in patients with minor but disabling stroke symptoms. Methods: 32 patients presenting with mild symptoms were treated with intravenous recombinant tissue-type plasminogen activator between April 2006 and April 2008. Data were extracted from a prospectively collected database. Baseline demographic data, and clinical, laboratory and imaging findings were analyzed. Outcome was assessed using the modified Rankin Scale (mRS) score at 3 months and was dichotomized into favorable (mRS 0–1) versus unfavorable (mRS 2–6). Results: In the majority of patients, the left hemisphere was affected, with aphasia representing the most common symptom leading to treatment decision. The frequency of perfusion lesion (46%) and vessel occlusion (35%) at baseline was high but had no effect on the outcome at 3 months in our series of treated patients. Outcome was favorable in 94% of patients, and 47% recovered without any persisting symptom. Only one asymptomatic and no symptomatic hemorrhage was observed. Conclusion: Our data support current guidelines and international licenses which give no lower National Institutes of Health Stroke Scale (NIHSS) limit for intravenous thrombolysis (IVT). Considering the accumulating evidence that the natural course in patients with mild symptoms is not as favorable as often assumed and taking the low risk of bleeding in those patients into account, patients with mild but disabling symptoms should be treated with IVT regardless of their baseline NIHSS score.

Clinical Course and Prognostic Factors in Acute Neck Pain: An Inception Cohort Study in General Practice

To describe the natural course of patients with acute neck pain presenting in general practice and to identify prognostic factors for recovery and sick leave. We conducted a prospective cohort study with a 1-year follow-up in general practice. Questionnaires were collected at baseline and after 6, 12, 26, and 52 weeks. Days of sick leave were dichotomized into two groups: below and above 7 days of sick leave. Logistic regression was used to identify prognostic factors for recovery and sick leave. Consecutive patients with nonspecific neck pain lasting no longer than 6 weeks were invited to participate. One hundred eighty-seven patients were included and 138 (74%) provided follow-up data. After 1 year, 76% of the patients stated to be fully recovered or much improved, although 47% reported to have ongoing neck pain. Almost half of the patients on sick leave at baseline returned to work within 7 days. Multivariate analysis showed that the highest association with recovery was the advice of the general practitioner (GP) "to wait and see" (odds ratio [OR] 6.7, 95% confidence interval [CI] 1.6-31.8). For sick leave, referral by the GP, for physical therapy or to a medical specialist, showed the highest association (OR 2.8, 95% CI 1.0-8.4). Acute neck pain had a good prognosis for the majority of patients, but still a relatively high proportion of patients reported neck pain after 1-year follow-up. The advice given by the GP "to wait and see" was associated with recovery, and "referral" was associated with prolonged sick leave.

Extrapulmonary small‐cell carcinoma compared with small‐cell lung carcinoma

The study was conducted with the aim of reviewing the clinical features, therapy, and natural course of patients with extrapulmonary small-cell carcinoma (EPSCC) and small-cell lung carcinoma (SCLC) to better define current concepts regarding EPSCCs. The medical records of patients with proven diagnosis of small-cell carcinoma (SmCC) between January 1999 and May 2006 were retrospectively reviewed. A total of 65 SmCC cases were included in the study (11 [17%] cases of EPSCC and 54 [83%] cases of SCLC). Progression-free survival of all patients with EPSCC and patients with extensive EPSCC disease was 7 months (95% confidence interval [CI], 0.58-13.42) and 7 months (95% CI, 4.71-13.29), respectively. Overall survival of all patients with EPSCC and patients with extensive EPSSC disease was 32 months (95% CI, 18.74-45.26) and 28 months (95% CI, 12.24-43.76), respectively. Progression-free survival and overall survival for all patients with SCLC were 5 months (95% CI, 2.26-7.74) and 10 months (95% CI, 5.95-14.05), respectively. Progression-free survival and overall survival for patients with extensive disease were 3 months (95% CI, 4.71-13.29) and 5 months (95% CI, 3.33-6.67), respectively. Overall survival was significantly better in all patients with EPSCC and in patients with extensive EPSCC disease compared with all patients with SCLC and patients with extensive SCLC disease (P = .014, P = .004, respectively). Early death and brain metastasis were observed in a higher number of patients with SCLC compared with EPSCC; however, these results were not statistically significant (P = .33 and P = .076, respectively). Smoking history was significantly less in the EPSCC group (P < .0001). EPSCC is usually treated similarly to SCLC. However, this study suggests some differences such as etiology, clinic course, survival, frequency of brain metastases, and early death between these entities. These possible differences may influence the choice of therapeutic approach.

Low Incidence of Adenocarcinoma and High Grade Dysplasia in Patients with Barrett's Esophagus: A Prospective Cohort Study

Background and Aims: Barrett's oesophagus (BE) is a premalignat condition and periodic endoscopic surveillance programme with biopsies is recommended. The real risk of development of high-grade dysplasia (HGD) or adenocarcinoma (AC) is a matter of discussion. Older studies probably overestimated the risk due to several shortcomings (definition of BE, definition of dysplasia, treatment of patients). The aim of our study was to investigate the incidence of low-grade dysplasia (LGD), HGD and AC in a cohort of patients with BE. Methods: A prospective, cohort study in 151 patients with BE. All patients had histologically confirmed intestinal metaplasia and macroscopic evidence of short (less then 3 cm) or long (equal or more than 3 cm) segment of BE. All patients underwent a standard protocol including regular endoscopic examinations with biopsies. Chromoendoscopy (or narrow band imaging) was used in all patients. The patients were treated with a high dose of a proton pump inhibitor (± H2-receptor antagonist) or underwent an antireflux surgery. One hundred thirty five patients were included into the analysis. Results: One hundred thirty five patients underwent 476 endoscopies during 527 patient-years of follow-up (mean 4.3). There were 45 subjects (33.3%) with long segment and 90 (66.7%) subjects with short segment BE. LGD was detected in 23 subjects (17%; in 14 patients with short and in 9 patients with long segment BE). In 9 of those patients, LGD was detected at index endoscopy (prevalent LGD) and in only 1 subject it has been detected during subsequent endoscopies. In remaining 14 patients, LGD was detected 1-7 years after an index endoscopy. At present, only 4 of them have LGD. Both HGD and AC were detected in one patient with long segment BE two years after an index endoscopy. The patient was treated with endoscopic mucosal resection and argon-plasma coagulation. Our study shows an incidence of HGD/AC in Barrett's oesophagus of 1 in 527 patient-years. Interestingly, the endoscopic regression of BE was seen in 28 (20.8%) of subjects while the mild progression only in 3 (2.2%) subjects. Conclusion: The incidence of HGD/AC in patients with BE being adequately treated is low - the annual risk of developing HGD/AC is 0.19% (0.68% in long segment BE). We hypothesised that an effective antisecretory treatment may change the natural course of patients with BE by decreasing the risk of development of HGD/AC.

Long-term follow-up and cost analysis following surgery for small bowel obstruction caused by intra-abdominal adhesions

This study examined the natural course of patients following surgery for small bowel obstruction (SBO) caused by abdominal adhesions. In addition, a cost analysis was performed. A retrospective analysis was undertaken of 102 patients who underwent surgery between 1987 and 1992 for intestinal obstruction due to abdominal adhesions. Median follow-up was 14 years. The 102 patients experienced 273 episodes of intestinal obstruction after the index operation, of which 237 involved inpatient readmissions; 47.3 per cent of the episodes resulted in further surgery. Single band adhesions were more common in patients with no previous abdominal surgery (P < 0.001). Some 52.0 per cent of the patients had undergone only one operation for SBO. A mean of 2.7 episodes per patient occurred after the index operation. The cost of adhesion-related problems in this study was 1,588,594 euros or 6702 euros per inpatient episode. The readmission rate in a selected cohort of patients with proven intra-abdominal adhesions was higher than reported previously. The annual cost of adhesion-related problems in Sweden was estimated as 39.9-59.5 million euros, and the cost of inpatient readmissions was almost equal to that for gastric cancer.

Intramedullary spinal cord metastases: a single-institution experience

Intramedullary spinal cord metastasis (ISCM) is the rarest type of CNS involvement of systemic malignant tumors. The aim of this retrospective study is to evaluate the clinical features, treatment and natural course of patients with ISCM in a single institution of Korea. We reviewed the medical records of all patients diagnosed with secondary malignant neoplasms involving the spinal cord at the Asan Medical Center between January 1995 and August 2006. Patients were diagnosed with ISCM if they had pathologically established malignancies originating outside the central nervous system (CNS), neurologic symptoms suggestive of spinal cord dysfunction, and either abnormal spinal MRI findings suggestive of ISCM or surgical or postmortem confirmation of ISCM. We excluded patients in whom ISCM was suspected because of known cancer and myelopathy, but with normal neuroimaging results. All 12 ISCMs arised from breast cancer (six patients) and lung cancer (three small cell lung cancer, three non-small cell lung cancer). Eight lesions were in the thoracic cord, one in the cervical cord, and three in both. In 11 patients, brain metastasis were combined with the development of ISCM. Initial symptoms included various paresthesias, sensory loss, and leg weakness. The duration of symptoms before diagnosis ranged from 2 days to 8 months (median, 7 days). Despite radiotherapy, neurologic status usually deteriorated rapidly, within a period of days to weeks. Median survival after ISCM diagnosis was 3.9 months (range 0.8-18.4 months) for all patients (breast cancer 5.5 months vs. lung cancer 1.0 month). Our findings indicate that ISCM is a very rare type of CNS involvement and represents a dismal finding of systemic malignancy. ISCM patients arising from breast cancer appeared to fare better than those with lung cancer.

Management of ascites and hepatic hydrothorax

The natural course of patients with cirrhosis is frequently complicated by the accumulation of fluid in the peritoneal or pleural cavities and interstitial tissue. Functional renal abnormalities that occur as a consequence of decreased effective arterial blood volume are responsible for fluid accumulation in the form of ascites and hepatic hydrothorax. Ascites is the most common complication of cirrhosis and poses an increased risk for infections, renal failure and mortality. Patients have a poor prognosis and it is estimated that nearly half will die in approximately 2 years without liver transplantation. Hepatic hydrothorax is defined as a pleural effusion greater than 500 mL (mostly right-sided) in patients with cirrhosis without cardiopulmonary disease; the estimated prevalence is approximately 5-10%. Liver transplantation is the most definitive cure for both conditions in those patients that are suitable candidates. However, the mainstay of therapy for minimizing fluid accumulation in both conditions includes sodium restriction and administration of diuretics. This article reviews the most current concepts of pathogenesis, clinical findings, diagnosis, and treatment of these complications of cirrhosis.

Vertebroplastie und Kyphoplastie bei osteoporotischen Wirbelkörperfrakturen: Gesicherte Kenntnisse, offene Fragen

Cementoplasty, performed either as percutaneous vertebroplasty or kyphoplasty, has become well established as an effective technique to treat painful vertebral body fractures. It has low complication rates, is successful in alleviating pain, and improves the patients' mobility and quality of life. A series of questions remain open though or are the subject of controversial debate; for example, the results of several biomechanical studies are in part contradictory. Clinical data on subsequent fractures are also still inadequate, although the majority of studies show no elevated rate of subsequent fractures following treatment with cementoplasty in comparison to the natural course in patients with osteoporotic fractures. Kyphoplasty has the advantage of being able to restore the vertebral body height or reduce the kyphosis angle without leading to different clinical outcomes in comparison to vertebroplasty. Biomechanical considerations on whether restoration of the vertebral body's normal shape could reduce the rate of subsequent fractures still need scientific substantiation. Both surgical methods are employed in our clinic. Kyphoplasty seems to us to be indicated when the height of the anterior portion of the vertebral body is reduced by one-third compared to the norm or a kyphosis angle of more than 15-20 degrees is present. The goals of therapy are restoring the shape and reducing the kyphosis angle. This can only succeed, however, in fractures that are not older than 3 weeks. In all other cases vertebroplasty is performed.

Tumor Necrosis Factor-α–238G&gt;A Promoter Polymorphism Is Associated With Increased Risk of New Hemorrhage in the Natural Course of Patients With Brain Arteriovenous Malformations

Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention. Patients with BAVM were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6-174G>C; IL-6-572G>C) and tumor necrosis factor-alpha (TNF-alpha-238G>A; TNF-alpha-308G>A). Association of genotype with risk of new ICH was screened using chi2; SNPs associated with new ICH were further characterized using Cox proportional hazards. We genotyped 280 patients (50% female; 59% white, mean+/-SD age at diagnosis 37+/-17 years; 40% presenting with ICH). TNF-alpha-238G>A was associated with increased risk of new ICH after diagnosis (chi2; P=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with TNF-alpha-238 AG genotype (hazard ratio, 4.01; P=0.015). No other SNP was found to be associated with new ICH. A TNF-alpha SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study.

TNFα−238G &gt; A Promoter Polymorphism is Associated With Increased Risk of New Hemorrhage in the Natural Course of Patients With Brain Arteriovenous Malformations

s: 33rd Annual Meeting of the Society of Neurosurgical Anesthesia and Critical Care: CBF/PHYSIOLOGY

To the Editor

In my article, I focused on the natural course of patients who do not receive any treatment. I believe, however, that the treatment results may shed some light on this disease. So I also examined a group who had undergone complete resection. This group was not the same as the nontreated group.

Longitudinal Risk of Intracranial Hemorrhage in Patients With Arteriovenous Malformation of the Brain Within a Defined Population

Accurate estimates for risk and rates of intracranial hemorrhage (ICH) in the natural course of patients harboring brain arteriovenous malformation (BAVM) are needed to provide a quantitative basis for planning clinical trials to evaluate interventional strategies and to help guide practice management. We identified patients with BAVM at the Kaiser Permanente Northern California health maintenance organization and documented their clinical course. The influences of age at diagnosis, gender, race-ethnicity, ICH at presentation, venous draining pattern, and BAVM size on ICH subsequent to presentation were studied using the multivariate Cox proportional hazards model and Kaplan-Meier curves. We identified 790 patients with BAVM (51% female; 63% white; mean age+/-SD at diagnosis: 38+/-19 years) between 1961 and 2001. Patients who presented with ICH experienced a higher rate of subsequent ICH than those who presented without ICH under multivariate analysis (hazard ratio, 3.6; 95% CI, 1.1 to 11.9; P<0.032). The effect was similar across race-ethnicity and gender. This difference in ICH rates was greatest in the first year (7% versus 3% per year) and converged over time. The effect of subsequent ICH on functional status was similar to that of the initial ICH. Presentation with ICH was the most important predictor of future ICH, confirming previous studies. Future ICH had similar impact on functional outcome as incident ICH. Intervention to prevent ICH would be of potentially greater benefit to patients presenting with ICH, although the advantage decreases over time.

Extrapulmonary small-cell carcinoma: a single-institution experience.

Extrapulmonary small-cell carcinoma (EPSCC) has been recognized as a clinicopathological entity distinct from small-cell carcinoma (SCC) of the lung. This study aimed to review the clinical features, therapy and natural course of patients with EPSCC in Oriental single-institution series. We retrospectively reviewed the medical records of patients with SCC between September 1995 and December 2002. Study eligibility required that patients had pathologically proven SCC in sites other than lung and normal radiological findings of the chest and normal sputum cytology or negative bronchoscopic findings. Twenty-four patients with EPSCC were identified and primary sites were various: uterine cervix in seven (29%), urinary bladder in five, colon or rectum in three, kidney in two and stomach, esophagus, pancreas, common bile duct, larynx, parotid gland, thymus in one each. Sixteen patients (66.7%) had limited disease (LD) and eight had extensive disease (ED). Patients with ED received mostly platinum-based chemotherapy, for which the response rate was 57%, but showed an aggressive natural history, with median overall survival (OS) of 9.2 months. Patients with LD were treated with a variety of therapeutic modalities. LD SCC of the cervix showed a favorable clinical course, with five patients being disease-free with a median follow-up of 28.4 months. Patients with LD SCC of sites other than cervix had an aggressive course with a median OS of 9.6 months. EPSCC was identified in various sites, with the most common primary site being the uterine cervix. Regardless of the primary site or disease stage, EPSCC of sites other than cervix was usually a fatal disease with a discouraging outcome for various treatment modalities.

Amino acid mutations in the interferon sensitivity determining region and serum virus load in hepatitis C virus carriers with long-term normal ALT levels

The amino acid mutations in a part of the non-structural region 5A (NS5A) of the hepatitis C virus (HCV) genome, called the interferon sensitivity determining region (ISDR), can affect the response to interferon (IFN) treatment. We analyzed the serial changes of the amino acid substitutions in the ISDR during the natural course of patients with sustained long-term normal alanine aminotransferase (ALT) levels in relation to the changes in virus load, and assessed the clinical significance of ISDR in the natural course and IFN treatment. The subjects were nine patients infected with HCV (genotype 1b) who had been examined for serum ALT levels every month for more than 1 year and had well-sustained normal levels. The amino acid sequence of the ISDR was determined by the direct sequencing method, and the number of amino acid mutations was evaluated in comparison with the prototype (HCV-J). Quantitation of serum HCV RNA levels was conducted by the Amplicor-monitor method (Nihon Roche). On the initial analysis of the ISDR, six patients were determined to have no mutations, and three patients had one or two mutations. However, an increased number in amino acid mutations compared with the wild type during the follow-up period was confirmed in only one patient, and that increase was limited to within two amino acids. Virus load changed regardless of the changes in amino acid substitutions in the ISDR. The ISDR was therefore inferred to be a stable region unrelated to the virus load in patients with well-sustained normal ALT levels. Additional changes of amino acid sequence in this region were not a sensitive marker for determining whether IFN treatment is indicated.

The follow-up of patients with unfavourable early results of transurethral prostatectomy.

To determine the natural course of patients with subjectively disappointing early results after transurethral prostatectomy (TURP), who experience prolonged discomfort and an initial deterioration in symptoms. A consecutive series of 127 patients undergoing urodynamic studies and TURP were assessed 3 months after surgery using symptom scores and measurements of urinary flow rate; 107 patients reported improved symptom and quality-of-life scores, but 20 did not improve, with no change or a deterioration. These 20 patients were followed for several months using symptom scores, and measurements of flow rates and residual urine volumes. Baseline variables, including preoperative urodynamic studies, were compared between those who improved and those who did not. Over a mean (range) follow-up of 10.6 (6-15) months, all those initially not improving showed spontaneous improvement in all three variables with no further treatment and eventually achieved the same significant degree of improvement as those who improved soon after TURP. Preoperatively, those initially not improving had mean lower symptom scores, more bladder irritability and less obstruction than did those who improved. A significant proportion (approximately 15%) of patients with obstructive symptoms will experience considerable symptomatic discomfort for a prolonged period after an uncomplicated TURP and will not gain the full symptomatic benefit from the procedure until 6-9 months afterward.

Indocyanine green angiographic features prognostic of visual outcome in the natural course of patients with age related macular degeneration

AIMSTo determine indocyanine green (ICG) angiographic features prognostic of visual acuity loss in eyes following a natural course of exudative age related macular degeneration (AMD).METHODS89 eyes of 72 patients (48...

Long-term follow-up of patients with severe rheumatic tricuspid stenosis

Background Tricuspid stenosis is a part of the chronically rheumatic heart. Although rare, when tricuspid stenosis does occur, it occurs in the setting of coexistent mitral and aortic valve disease. The natural course of patients with severe tricuspid stenosis is not well defined. The aim of this study is to present close follow-up of patients with chronic rheumatic heart disease and severe tricuspid stenosis. Methods and Results We retrospectively studied 13 patients (11 women and 2 men) with severe tricuspid stenosis who were followed closely for 6 to 31 years. The mean tricuspid pressure gradient ranged from 3 to 9 mm Hg. Twelve patients underwent surgery for mitral and/or aortic valve lesions without complications. Concomitant tricuspid valve surgery was performed on six patients: two De Vega procedures, two Kay plications, and two implantations of Carpentier rings. All these also had leaflet commissurotomy. After surgery, the mean tricuspid gradient decreased in three patients, did not change in two, and increased in one. All 13 patients were treated with diuretics, digoxin, warfarin, and spirinolactone or ACE inhibitors. On their last follow-up visit, every patient had increased jugular venous pressure. Hepatomegaly was found in 6 of 13, leg edema in 4 of 13, and ascites in 1 of 13. Conclusions Most tricuspid stenosis patients are women with severe mitral and aortic valve disease. After successful repair of the mitral or aortic valve, and regardless of the type of tricuspid valve surgery, severe tricuspid stenosis was found to be very well tolerated by all the patients over many years of follow-up. (Am Heart J 1998;136:103-8.)

Outcome after local intra-arterial fibrinolysis compared with the natural course of patients with a dense middle cerebral artery on early CT.

Our purpose was to relate the outcome after local intra-arterial fibrinolysis (LIF) to the natural course in middle cerebral artery (MCA) occlusion. We retrospectively studied 40 patients with a dense middle cerebral artery on early CT; 20 were treated with LIF within 6 h of onset of symptoms, 20 received "conventional" stroke therapy. The dense middle cerebral artery, which is regarded as a highly specific indicator of thromboembolic MCA occlusion, was chosen as inclusion criterion since patients with "conventional" stroke therapy were not exposed to cerebral angiography. Patients treated with LIF had a significantly better outcome using the Barthel index (P = 0.025): there was a 30% increase in the proportion of patients with minimal or no disability. Mortality, however, did not differ significantly (P = 0.7). Two fatal haemorrhages occurred in the LIF group, and one haemorrhagic transformation in the "conventional" group. Leptomeningeal collateralisation correlated significantly with outcome in the LIF group (P = 0.04). Although the relation between outcome and interval from onset of symptoms to LIF was not significant (P = 0.74), all patients treated within 3 h had an excellent outcome.

Progression of Visual Field Loss in Patients with Retinitis pigmentosa of Sporadic and Autosomal Recessive Types

Purpose: We examined the natural course of patients with retinitis pigmentosa of the eight sporadic and five autosomal recessive forms over 5 years. Methods: We measured the areas of the visual fields by Goldmann perimetry using a digitizer and a computer software. Results: The visual field of V-4 isopters in 4 sporadic cases was approximately 200 cm² during 30 years after the initial examination, but decreased down to 40 cm² in the next 10 years. The visual field was reduced to half the normal field in 3 autosomal recessive cases early below the age of 25 years. In 4 sporadic and 2 autosomal recessive cases, the inferior temporal visual field was the widest at the onset of the disease, but exhibited the most severe loss. The superior nasal area was the narrowest initially, and showed the mildest progression. Conclusions: The visual field in retinitis pigmentosa is constricted age-dependently with severe loss of the inferior temporal visual area and mild damage to the superior nasal area.

Natural history of distal spinal agenesis.

We studied the natural course in patients with distal spinal agenesis (DSA). Specifically, we compared children with different types of DSA (Renshaw sacral agenesis types I-IV) and determined their maximum ambulatory abilities, identified patients at risk for decubiti, determined the average number of operations per patient, described associated congenital anomalies, and sought a correlation between different types of DSA and the risk of back pain and development of scoliosis. Through a retrospective analysis, we concluded that there are definite correlations between the specific type DSA and the natural course with regard to all these entities.