Scoring Systems May be Effective in Predicting Mortality Associated with Palliative Emergency Gastrointestinal Surgery: A Retrospective Observational Study.

BACKGROUND: Palliative emergency gastrointestinal surgery is associated with significant morbidity and mortality and weighing up the benefits and harms during the decision-making may be challenging. There are very few studies on surgery in palliative patient population. The aim of this retrospective study was to evaluate morbidity and mortality after palliative emergency gastrointestinal surgery and the usability of scoring systems in predicting the outcome. METHODS: Consecutive adult patients undergoing palliative emergency surgery at a tertiary hospital during the period 2015 to 2016 were included. Pre- and post-operative functional status, morbidity and mortality of patients were assessed. The predictive value of the American Society of Anesthesiologists (ASA) classification, the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator (ACS NSQIP SRC) and Palliative index (PI) in estimating morbidity and mortality were determined. RESULTS: A total of 93 patients (age 69 [28-92] years, 51% female) were included. Typical indications for surgery were bowel obstruction (52%) and securing food intake (30%). Pre-operatively two patients (2.2%) were totally dependent in daily activities, while post-operatively the respective share was 34% at discharge from hospital. The incidence of post-operative complications was 37% and 14% died during the hospital stay. One-, three-month and one-year mortality rates were 41%, 63% and 87%, respectively. While ASA score, PI score and ACS NSQIP did not predict post-operative morbidity, both ASA score and ACS NSQIP SRC predicted post-operative mortality. CONCLUSIONS: Palliative emergency laparotomy is associated with significant post-operative mortality and morbidity. Scorings, such as ASA score and ACS NSQIP SRC predict mortality in this patient population.

The Occurrence of Lung Cancer and Non-Pulmonary Malignancies After Pleural Infections.

BACKGROUND AND AIMS: Patients who develop infections of the pleura have several risk factors for malignancies, particularly lung cancer, and the infections might even be caused by undiagnosed intra-thoracic neoplasms. The aim of the study was to compare the occurrence of lung cancer and other malignancies between patients treated for pleural infections and controls during long-term follow-up. MATERIALS AND METHODS: All consecutive patients treated for pleural infections between January 2000 and June 2016 at the Tampere University Hospital were included. Ten matched controls and data regarding later cancer diagnoses were requested from national registries. The cancer types and rates, the diagnostic delays, as well as survival were compared between patients and controls. RESULTS: The material comprised 506 patients and 5022 controls (78% was male and median age was 60 years in both groups) with a median follow-up time of 69 months. In total, 74% of pleural infections were related to pneumonia. The occurrence of lung cancer during follow-up was 3.0% in all patients, 2.2% in pneumonia-related cases, and 0.6% in controls, p < 0.001 when compared with controls. The overall rate of non-pulmonary malignancies did not differ. Lung cancer was diagnosed within 3 months in 73% of patients versus in 6.9% of controls, p < 0.001. The survival in patients with later lung cancers or other malignancies was inferior to that of controls with similar neoplasms. CONCLUSION: The rate of lung cancer diagnoses was significantly increased in patients treated for pleural infections when compared with matched controls and the prognosis of patients with subsequent malignancies was impacted.

Nighttime Appendectomy is Safe and has Similar Outcomes as Daytime Appendectomy: A Study of 1198 Appendectomies.

INTRODUCTION: Although it is controversial whether appendectomy can be safely delayed, it is often unnecessary to postpone operation as a shorter delay may increase patient comfort, enables quicker recovery, and decreases costs. In this study, we sought to study whether the time of day influences the outcomes among patients operated on for acute appendicitis. MATERIALS AND METHODS: Consecutive patients undergoing appendectomy at Tampere University Hospital between 1 September 2014 and 30 April 2017 for acute appendicitis were included. Primary outcome measures were postoperative morbidity, mortality, length of hospital stay, and amount of intraoperative bleeding. Appendectomies were divided into daytime and nighttime operations. RESULTS: A total of 1198 patients underwent appendectomy, of which 65% were operated during daytime and 35% during nighttime. Patient and disease-related characteristics were similar in both groups. The overall morbidity and mortality rates were 4.8% and 0.2%, respectively. No time categories were associated with risk of complications or complication severity. Neither was there difference in operation time and clinically significant difference in intraoperative bleeding. Patients undergoing surgery during night hours had a shorter hospital stay. In multivariate analysis, only complicated appendicitis was associated with worse outcomes. DISCUSSION: We have shown that nighttime appendectomy is associated with similar outcomes than daytime appendectomy. Subsequently, appendectomy should be planned for the next available slot, minimizing delay whenever possible.

Trends in the Incidence, Etiology, Treatment, and Outcomes of Pleural Infections in Adults Over a Decade in a Finnish University Hospital.

BACKGROUND AND AIMS: The aim of the study was to ascertain changes in the incidence, etiology, treatment, and outcomes of pleural infections over a decade in a Finnish University Hospital. MATERIALS AND METHODS: All patients treated for pleural infections in Tampere University Hospital during 2000-2008 and 2012-2016 were included. The incidence rates and the epidemiologic data and medical history of patients, etiology of infection, and treatment trends and outcomes were compared between the cohorts. RESULTS: The incidence of pleural infections increased from 4.4 during 2000-2008 to 9.9 during 2012-2016 per 100.000 patient-years, p < 0.001. The patients in the latter group were older, 63 versus 57 years, p = 0.001, and the prevalence of chronic lung disease, hypertension, heart failure, dyslipidemia, and immunosuppressive medication were higher. The causes of infection remained similar and pneumonia accounted for 70% of all cases. The identification rate of the microbe pathogens increased from 49% to 64%, p = 0.002, while the distribution of identified pathogens was unchanged. More patients in the latter cohort were treated operatively, 88.3% versus 80.9%, p = 0.005, and, in these, the proportion of thoracoscopic surgery was higher, 57.4% versus 8.0%, p < 0.001, and the delay to surgery shorter, 5 versus 7 days, p < 0.001. Radiologic outcomes were similar. The 30-day mortality rate was 3.1% during 2000-2008 and 5.1% during 2012-2016, p = 0.293. CONCLUSION: The overall incidence of pleural infections has increased significantly while the causes of pleural infections and the distribution of pathogens remain unchanged. Contemporary patients are older with higher prevalence of comorbidities and more frequently undergo thoracoscopic surgery.

Long-Term Prognosis and Causes of Death After Pleural Infections.

BACKGROUND AND AIMS: The development of pleural infection may imply a worse state of health and prognosis. The objective of this study was to ascertain the long-term survival and causes of death after pleural infections and to compare them to those of matched controls. MATERIAL AND METHODS: Altogether 191 patients treated for pleural infections at a single University Hospital between January 2000 and December 2008 and 1910 age- and gender-matched controls were included. Survival data and the causes of death for non-survivors were obtained from national databases and compared between the groups. RESULTS: The etiology of pleural infection was pulmonary infection in 70%, procedural complication in 9%, trauma in 5%, malignancy in 4%, other in 7%, and unknown in 5% of patients. The course of treatment was surgical in 82%, drainage only in 12%, and conservative in 5% of included patients. The median follow-up time was 11 years. Mortality rates were 8.4% versus 0.8% during the first 90 days, p < 0.001, and 46.6% versus 24.5% overall, p < 0.001, in patients and controls, respectively. Mortality was significantly higher in patients with pulmonary infection, procedural complication, or malignancy as the etiology of pleural infection. In multivariable analysis, advanced age, previous malignancies, institutional care, alcoholism, and malignant etiology for the infection were associated with inferior survival. Deaths caused by malignancies, respiratory diseases, and digestive diseases were significantly more common in patients than in controls. CONCLUSION: Long-term survival in patients with pleural infections is significantly inferior to that of age and gender-matched controls.

Cognitive dysfunction in primary progressive multiple sclerosis: a neuropsychological and MRI study.

Although cognitive dysfunction is known to occur in multiple sclerosis (MS), only few studies have reported cognitive performance in patients with primary progressive MS (PPMS). To find out the pattern of cognitive performance in PPMS, 28 PPMS patients underwent an extensive battery of neuropsychological tests. The results were compared to those of healthy controls (n = 20) and patients with secondary progressive MS (SPMS, n = 28). Furthermore, the results of neuropsychological tests in PPMS were correlated to magnetic resonance imaging findings. Our study showed that the PPMS patients have deficits in several cognitive domains when compared to age-matched and education-matched controls, but the cognitive impairment in the PPMS and SPMS patients appeared to be similar. Cognitive deficits in PPMS patients correlated with diffuse brain lesion, T1- and T2-lesion load, but no correlations were found with atrophy.

Once-weekly 22microg subcutaneous IFN-beta-1a in secondary progressive MS: a 3-year follow-up study on brain MRI measurements and serum MMP-9 levels.

OBJECTIVE: To study the effect of weekly injected subcutaneous interferon (IFN)-beta-1a 22 microg on the extent of brain lesions on magnetic resonance imaging (MRI) and the level of serum matrix metalloproteinase (MMP)-9 in patients with secondary progressive multiple sclerosis (SPMS). SUBJECTS AND METHODS: All the 28 Finnish patients participating in the Nordic multicentre trial on the clinical efficacy of weekly IFN-beta-1a (Rebif) 22 microg in SPMS were studied neurologically and by volumetric MRI during a 3-year follow-up. The levels of MMP-9 in serum were measured over the 3-year study. RESULTS: There was no obvious effect on the number of contrast medium-enhancing lesions, the volume of T1 or T2 lesions or level of serum MMP-9, nor was any effect detected on the relapse rate and the Expanded Disability Status Scale (EDSS). Brain atrophy progression was not affected by the treatment. CONCLUSION: The lack of effect on MRI, clinical outcomes or the levels of MMP-9 indicates that subcutaneous administration of low-dose low-frequency IFN-beta-1a is insufficient in controlling either the inflammatory constitutes or the neurodegenerative changes of advanced SPMS.

Increased disability and MRI lesions after discontinuation of IFN-beta-1a in secondary progressive MS.

OBJECTIVE: To examine neurological and magnetic resonance imaging (MRI) changes following discontinuation of interferon (IFN)-beta-1a treatment in secondary progressive multiple sclerosis (SPMS). METHODS: The study involved 21 SPMS patients who received subcutaneous (s.c.) IFN-beta-1a 44 microg three times weekly (t.i.w.) for 12 months and were thereafter followed up without treatment for a further 12 months. The number of relapses, disability on the Expanded Disability Status Scale (EDSS) and MRI were recorded at baseline, at 12 months of IFN-beta-1a 44 microg t.i.w. and 1 year after discontinuation of treatment. RESULTS: During the 12-month treatment EDSS score and volumes of brain T2- and T1-weighted lesions remained without significant progression, but at 12 months after treatment discontinuation both EDSS score and the volumes of cerebral lesions increased significantly. Cerebrospinal fluid fraction increased significantly both during the treatment and during follow-up. CONCLUSIONS: Discontinuation of IFN-beta-1a 44 microg t.i.w. in SPMS may be associated with an increase in neurological disability and brain lesions on MRI.

Urodynamic findings in primary progressive multiple sclerosis are associated with increased volumes of plaques and atrophy in the central nervous system.

OBJECTIVE: Voiding dysfunction is more frequent in primary progressive multiple sclerosis (PPMS) than in other subtypes of MS. We investigated whether lower urinary tract disorders are reflected in the extent of changes in brain and spinal cord detected by magnetic resonance imaging (MRI). METHODS: Micturition symptoms and specific urodynamic findings in 24 patients with PPMS were related to MRI abnormalities as analysed by segmentation and volumetric analysis. RESULTS: Urgency and urge incontinence were the most frequent urinary symptoms (83 and 75 %), while detrusor sphincter dyssynergia (DSD) (71%), detrusor hyperreflexia (58%) and obstruction (58%) were the most common micturition dysfunctions. Comparison between patients with detrusor hyperreflexia and those with normal bladder function revealed higher volumes of T2-weighted plaques in the brains of former (P = 0.01). In patients with hypotonic bladder the total brain volume was smaller (P = 0.02) and the number of thoracic plaques in T2-weighted images higher (P = 0.02) compared to patients with normal bladder function. Furthermore, DSD was associated with a higher volume of T2-weighted plaques in the brain (P = 0.02). CONCLUSIONS: Voiding dysfunction in PPMS is associated with increasing brain and spinal cord abnormalities. Urodynamic investigation is, however, needed for specific definition of micturition disturbances and should be made before therapeutic decisions.

Volumetric quantitation by MRI in primary progressive multiple sclerosis: volumes of plaques and atrophy correlated with neurological disability.

In primary progressive multiple sclerosis (PPMS) abnormalities in brain magnetic resonance imaging (MRI) differ from abnormalities in other subtypes of multiple sclerosis (MS). It was investigated whether the extent of brain and spinal cord MRI abnormalities is reflected in the neurological disability in PPMS. Focal and diffuse changes and atrophy in central nervous system (CNS) in patients with PPMS (n = 28) and healthy controls (n = 20) were assessed by semi-automatic MRI segmentation and volumetric analysis. The measurements were related to neurological disability as expressed by the expanded disability status scale (EDSS), the regional functional scoring system (RFSS), the arm index and the ambulation index. Plaques in T1- and/or T2-weighted images were seen in all brains, while spinal plaques were detected in 23 of 28 patients (82%). The total volumes of brain and spinal cord were significantly smaller in patients than in controls (P = 0.001 and 0.000, respectively). The volumes of T1 or T2 lesions in the brain correlated to the ambulation index (r = 0.51, P = 0.005 and r = 0.53, P = 0.004, respectively). No correlations were detected between MRI measurements and total EDSS score, but relative brain atrophy correlated inversely with the total RFSS scores, poor arm index and higher cerebral disturbances (r = -0.53, P = 0.004; r = -0.53, P = 0.004; and r = -0.52, P = 0.005, respectively). Although the number of spinal T2 lesions correlated with sensory disturbances (r = 0.60, P = 0.001), no correlations were found between EDSS subscores and spinal cord atrophy. These findings show that marked atrophy of brain and spinal cord detected by volumetric quantitation correlates with neurological disability. This observation indicates the importance of neurodegenerative events in PPMS.

Promoter polymorphism of IL-10 and severity of multiple sclerosis.

Functional polymorphisms of the genes for interleukin-10 (IL-10; promoter position -1082), chemokine receptor-5 (CCR5 32 bp deletion), tumor necrous factor-alpha (TNFalpha promoter position -308) and cytotoxic T-lymphocyte antigen-4 (CTLA-4 exon 1 position 49) were investigated for possible influence on susceptibility and outcome of multiple sclerosis (MS). The polymorphisms were typed by polymerase chain reaction based methods or by direct sequencing in MS patients (n=93-116) and controls (n=109-400). The studied genes were not associated with MS susceptibility. Patients were classified as suffering from a mild/moderate [Expanded Disability Status Scale (EDSS) 0-5.5] or severe (EDSS 6-8.0) form of MS. The AG genotype of IL-10 proved to be protective against severe MS in all patients (OR=0.32, P=0.010), the effect being increased over the years (10 years; OR=0.33, P=0.043, 15 years; OR=0.21, P=0.025 or 20 years; OR=0.14, P=0.026). Our results suggest that differential production of IL-10 might be a factor in the severity of MS.

Increased nitric oxide products in CSF in primary progressive MS may reflect brain atrophy.

Because nitric oxide (NO) is a putative mediator of oligodendrocyte damage in the primary progressive form of MS (PPMS), the authors analyzed the levels of NO oxidation products in CSF and plasma from 25 patients with PPMS and 15 controls. The levels of nitrite + nitrate (NOx) in CSF were fourfold higher in patients with PPMS than in controls (p < 0.001), whereas the concentrations in plasma were similar. These data suggests involvement of NO in nervous tissue damage in PPMS.

A study of interleukin-1 cluster genes in susceptibility to and severity of multiple sclerosis.

In this explorative study, interleukin-1 (IL-1) receptor antagonist (IL-1RA; polymorphism of variable number of tandem repeats: VNTR), IL-1alpha (-889), IL-1beta (-511) and IL-1beta (+3953) polymorphisms were studied in relation to susceptibility to and severity of multiple sclerosis (MS), in 93 MS patients and 400 normal controls. No associations were found for any polymorphisms, alone or in combination. However, in our MS cohort, females were found to be IL-1RA allele 2 carriers more frequently than males (33/49 vs. 16/44, p = 0.0028). Using a cohort of 109 controls, IL-1RA allele 2 carriers were more frequently women with MS than control women (33/49 vs. 23/43, odds ratio (OR) = 2.19, 95% confidence interval (CI) 1.02-4.72, p = 0.043, P(C) = ns). The data suggest that the IL-1 cluster genes make no major contribution to MS, but the tentative association between IL-1RA allele 2 and susceptibility of MS in women warrants further studies.

The combination of HLA-DR1 and HLA-DR53 protects against MS.

The DRB1/3/4/5 loci from 97 patients with MS and 100 normal control subjects were analyzed. DRB1*15 increased the risk of MS (OR = 4.2, p < 0.0001), whereas DR1 decreased the risk (OR = 0.30, p(c )= 0.005). In analyses of the DR1 risk in relation to DR51, DR52, and DR53 alleles, DR1 in combination with DR53 was found to have the strongest protective effect against MS in all subjects (OR = 0.05, p < 0.0001) and in DRB1*15-negative subjects (OR = 0.09, p(c )= 0.026). DR53 may be an important allele or haplotype, acting together with DR1 to protect against MS.

Plasminogen activator inhibitor 1 gene and risk of MS in women.

In view of the potential importance of the proteolytic mechanisms in the evolution of MS lesions, the authors studied the 4G/5G promoter polymorphism of the plasminogen activator inhibitor 1 (PAI-1) gene in the susceptibility of MS. The 5G5G genotype was associated with MS in women at an odds ratio of 2.3 (95% confidence interval, 1.04 to 5.23). The genotype seems to be a low producer of PAI-1, suggesting that reduced capacity for proteinase inhibition may be involved in the etiopathogenesis of MS in women.

Adhesion molecules in multiple sclerosis: relation to subtypes of disease and methylprednisolone therapy.

OBJECTIVES: To determine levels of adhesion molecules in blood and cerebrospinal fluid (CSF) samples from patients with different subtypes and activities of multiple sclerosis (MS) and to assess the effect of intravenous methylprednisolone sodium succinate treatment on the levels of soluble adhesion molecules. DESIGN: The expressions of very late activation antigen 4 (VLA-4), lymphocyte function associated antigen 1 (LFA-1), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) were determined immunocytochemically, and levels of soluble VCAM-1, ICAM-1, and E-selectin, by means of enzyme immunoassay technique. The volumes of T2- and T1-weighted MS plaques and brain atrophy were determined by means of the semiautomatic magnetic resonance imaging (MRI) segmentation technique. SETTING: A university hospital in Finland. PATIENTS: One hundred subjects (71 patients with MS and 29 healthy control subjects). The subtypes of MS were relapsing-remitting (RRMS [n = 26]), secondary progressive (SPMS [n = 20]), and primary progressive (PPMS [n = 25]). RESULTS: In patients with RRMS and SPMS, the expressions of VLA-4 and LFA-1 on immune cells from blood were at least 1.5- to 3-fold higher than in controls (RRMS, P = .002 and P<.001, respectively; SPMS, P = .03 and P =.001, respectively). In RRMS, LFA-1 and ICAM-1 expression in blood was more up-regulated than in SPMS (P = .03 and P = .01, respectively). The expressions of adhesion molecules on CSF lymphocytes in RRMS and SPMS were of similar magnitude, but the proportions of CSF VLA-4- and LFA-1-expressing lymphocytes were 3- to 4-fold higher than in controls (P = .04 and P = .008, respectively). The levels of serum soluble VCAM-1 were higher in SPMS than in RRMS (P = .005) or PPMS (P = .04). Intravenous methylprednisolone treatment of patients with RRMS in exacerbation caused a significant reduction in the serum levels of soluble VCAM-1 and E-selectin (P<.001). In SPMS, the volumes of T2-weighted plaques correlated with the serum level of soluble ICAM-1 (r = 0.64; P = .03). CONCLUSIONS: Up-regulated adhesion molecules in blood and CSF indicate sustained potential for inflammation in the CNS throughout the clinical spectrum of MS. Therapies interfering with cell adhesion may be of key importance in suppressing MS.

Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis.

The objectives of the present study was to correlate the segmented magnetic resonance imaging (MRI) volumes of intracranial cerebrospinal fluid (CSF) spaces (expressing the extent of brain atrophy) and cerebral plaques with the neurological disability in secondary progressive multiple sclerosis (MS). Earlier studies have mainly correlated MS plaques and neurological disability measured by expanded disability status scale (EDSS). The data on the association between brain atrophy and EDSS or regional functional scoring scale (RFSS) are very limited. We measured the volumes of intracranial CSF spaces in 28 patients with secondary progressive MS using MRI, and semiautomatic segmentation software. The volumes of T1-weighted hypointense and T2-weighted hyperintense MS plaques were also measured. In multiple regression analysis, increasing volumes of total (P=0.006) and relative (P=0.005) intracranial CSF spaces were significantly associated with worsening neurological disability as expressed by EDSS. No associations were found between these intracranial CSF space volumes and total RFSS scores. The mean volume of T2-weighted plaques showed a tendency to associate with total RFSS score (r=0.40, P=0.03), but no correlations were detected between T1- or T2-weighted plaque volumes and EDSS. The application of a new segmentation technique in quantifying intracranial cerebrospinal fluid spaces allowed an exact and sensitive way of assessing brain atrophy. The associations between brain atrophy and neurological disability expressed by EDSS suggests that the effect of MS therapies should be evaluated by measurement of brain atrophy.