SuPAR in major depression: Association with 26 weeks antidepressant response and 10-year depression outcomes.

Introduction: Inflammation has been associated with depression and differential antidepressant (AD) treatment response. Soluble urokinase plasminogen activator receptor (suPAR) is a novel measure of chronic inflammation. We investigated whether suPAR is associated with depression severity and AD response. Methods: We included 90 patients with major depressive disorder (MDD) who participated in a part-randomized clinical trial of 26 weeks of treatment with escitalopram or nortriptyline. suPAR levels were measured in serum samples collected at baseline and after 8, 12 and 26 weeks. Mixed effects models for the association between suPAR levels and AD response were performed. By merging with Danish nationwide registers, we included information on psychiatric hospital contacts during ten years after the GENDEP trial. Cox regression analyses calculated the hazard rate ratios between suPAR levels and subsequent hospitalizations. Results: At baseline, higher suPAR levels were not associated with overall depression severity but with greater severity of neurovegetative depressive symptoms, specifically appetite and weight changes. 57 (63.3%) patients responded positively to treatment. Among 57 (63.3%) patients who achieved response, those who responded had significantly higher baseline suPAR levels levels, and response was associated with a significant decrease in suPAR during AD treatment. Remitters decreased from 3.1 ng/ml at baseline to 2.8 ng/ml after 26 weeks (p = 0.003) and responders from 3.0 to 2.8 ng/ml (p = 0.02), whereas non-remitters and non-responders showed unchanged suPAR levels. We found no correlation between a change in suPAR and a change in MADRS, but a lowering of suPAR correlated with a decrease in neurovegetative symptoms. We found no association between suPAR levels and 10-year risk for hospitalizations. Discussion: The present study suggests that an elevated level of chronic inflammation, measured as the suPAR level, is associated with better response to AD treatment.

Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials.

BACKGROUND: No study has gathered evidence from all randomized clinical trials (RCTs) with anti-inflammatory drugs measuring antidepressant effects including a detailed assessment of side-effects and bias. METHODS: We performed a systematic review identifying RCTs published prior to January 1, 2018, studying antidepressant treatment effects and side-effects of pharmacological anti-inflammatory intervention in adults with major depressive disorder (MDD) or depressive symptoms. Outcomes were depression scores after treatment, remission, response, and side-effects. Pooled standard mean differences (SMD) and risk ratios (RR) including 95% confidence intervals (95%-CI) were calculated. RESULTS: We identified 36 RCTs, whereof 13 investigated NSAIDs (N = 4214), 9 cytokine inhibitors (N = 3345), seven statins (N = 1576), 3 minocycline (N = 151), 2 pioglitazone (N = 77), and 2 glucocorticoids (N = 59). Anti-inflammatory agents improved depressive symptoms compared to placebo as add-on in patients with MDD (SMD = -0.64; 95%-CI = -0.88, -0.40; I2  = 51%; N = 597) and as monotherapy (SMD = -0.41; 95%-CI = -0.60, -0.22; I2  = 93%, N = 8825). Anti-inflammatory add-on improved response (RR = 1.76; 95%-CI = 1.44-2.16; I2  = 16%; N = 341) and remission (RR = 2.14; 95%-CI = 1.03-4.48; I2  = 57%; N = 270). We found a trend toward an increased risk for infections, and all studies showed high risk of bias. CONCLUSION: Anti-inflammatory agents improved antidepressant treatment effects. Future RCTs need to include longer follow-up, identify optimal doses and subgroups of patients that can benefit from anti-inflammatory intervention.

Mortality in unipolar depression preceding and following chronic somatic diseases.

OBJECTIVE: It is largely unknown how depression prior to and following somatic diseases affects mortality. Thus, we examined how the temporal order of depression and somatic diseases affects mortality risk. METHOD: Data were from a Danish population-based cohort from 1995 to 2013, which included all residents in Denmark during the study period (N = 4 984 912). Nineteen severe chronic somatic disorders from the Charlson Comorbidity Index were assessed. The date of first diagnosis of depression and somatic diseases was identified. Multivariable Cox proportional Hazard models with time-varying covariates were constructed to assess the risk for all-cause and non-suicide deaths for individual somatic diseases. RESULTS: For all somatic diseases, prior and/or subsequent depression conferred a significantly higher mortality risk. Prior depression was significantly associated with a higher mortality risk when compared to subsequent depression for 13 of the 19 somatic diseases assessed, with the largest difference observed for moderate/severe liver disease (HR = 2.08; 95% CI = 1.79-2.44), followed by metastatic solid tumor (HR = 1.48; 95% CI = 1.39-1.58), and myocardial infarction (HR = 1.40; 95% CI = 1.34-1.49). CONCLUSION: A particularly high mortality risk was observed in the presence of prior depression for most somatic diseases. Future studies that assess the underlying mechanisms are necessary to adequately address the excessive mortality associated with comorbid depression.

C-reactive protein and white blood cell levels in schizophrenia, bipolar disorders and depression - associations with mortality and psychiatric outcomes: a population-based study.

BACKGROUND: Mental disorders have been associated with increased levels of inflammatory markers, which can affect disease trajectories. We aimed to assess levels of C-reactive protein (CRP) and white blood cells (WBC) across individuals with schizophrenia, bipolar disorder, and depression, and to investigate associations with subsequent psychiatric admission and mortality. METHODS: We identified all adults in the Central Denmark Region during 2000-2012 with a first diagnosis of schizophrenia, bipolar disorder, or depression and a baseline measurement of CRP and/or WBC count. We followed these individuals until outcome of interest (psychiatric admission or death), emigration or December 31, 2012, using Cox regression analysis to estimate hazard ratios (HRs). RESULTS: Baseline median CRP differed significantly between mental disorders (P=0.01) being highest in individuals with bipolar disorder (3.5mg/L) (particularly during manic states, 3.9mg/L), followed by schizophrenia (3.1mg/L), and depression (2.8mg/L), while baseline WBC count did not differ (median 7.1×109/L). Elevated CRP levels were associated with increased all-cause mortality by adjusted HRs of 1.56 (95% CI: 1.02-2.38) for levels 3-10mg/L and 2.07 (95% CI: 1.30-3.29) for levels above 10mg/L compared to individuals with levels below 3mg/L. WBC counts were not associated with all-cause mortality. No association was observed between levels of the inflammatory markers and subsequent psychiatric admissions. CONCLUSIONS: People with severe mental disorders had increased inflammatory markers at first diagnosis, and elevated CRP levels were associated with increased mortality. Thorough screening for physical diseases is of utmost importance among individuals who are diagnosed with severe mental disorder.

Secondary aortoenteric fistulae--changes from 1973 to 1993.

AIM: To investigate a series of patients with secondary aortoenteric fistulas and compare it with a previous series (1985-93 vs. 1973-84). DESIGN: Retrospective study of medical records. SETTING: Sixteen vascular surgical centers in Sweden. PATIENTS: Twenty-seven patients were identified making an overall incidence of 0.5% of all aortoiliac operations. Among aneurysm patients the incidence was significantly lower than in the previous series. One patient record could not be identified. Fourteen primary operations were for aortic aneurysm, 12 for occlusive disease and one was an aortorenal vein bypass. RESULTS: Symptoms of the fistula occurred after a median interval of 90 months which is significantly later than the previous series (32 months; p<0.05). The commonest presentation was bleeding followed by septis. The median diagnostic delay was 10.5 days, which was significantly shorter than in the previous series. Most fistulas involved the duodenum (88%). One patient died before surgery. The postoperative mortality was 28%, significantly lower than in the previous series (58%) (p<0.05). At the end of follow up (median 43 months) significantly more patients were alive than in the previous series (42% vs 18%) (p<0.05). CONCLUSION: Over a 21 year period there seems to have been a decrease in the frequency of secondary aortoenteric fistulas after aneurysm surgery, a longer interval before they occur, a shorter diagnostic delay, and a better survival.

Abdominal aortic aneurysm with perianeurysmal fibrosis: experience from 11 Swedish vascular centers.

Case records of 2026 patients operated on because of abdominal aortic aneurysms from 11 Swedish Vascular Centers were reviewed and revealed 98 cases (4.8%) of inflammatory abdominal aortic aneurysm. Also included in this case-control study was an analysis of a randomized group of 82 patients from the same centers who had noninflammatory abdominal aortic aneurysms. Four inflammatory aneurysms were ruptured, compared with 16 in the noninflammatory group (p less than 0.01). A higher proportion of patients with inflammatory abdominal aortic aneurysms had symptoms that led to radiographic investigations. The median erythrocyte sedimentation rate was 39 mm versus 19 mm (26% of patients with inflammatory abdominal aortic aneurysms had erythrocyte sedimentation rates greater than 50 mm; p less than 0.001), and the serum creatinine level was increased in 27 and 8 patients (p less than 0.01) in the inflammatory and noninflammatory groups, respectively. Preoperative investigations revealed ureteral obstruction in 19 patients with inflammatory abdominal aortic aneurysms, of whom 12 had preoperative nephrostomy or ureteral catheter placement. At operation, 20 additional patients exhibited fibrosis around one or both ureters. Although ureterolysis was performed in 19 patients, preoperative and postoperative creatinine levels did not differ between these patients and the conservatively treated ones. Duration of surgery (215 vs 218 minutes), intraoperative blood loss (2085 vs 2400 ml) and complications did not differ significantly between the groups. Overall operative (30-day) mortality was equal (11% vs 12%) but was increased for patients undergoing elective surgery for inflammatory abdominal aortic aneurysms (9% vs 0%; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesic efficacy of acetaminophen sustained release.

The analgesic efficacy of acetaminophen sustained release (SR) and acetaminophen immediate plus sustained release (IR + SR) was evaluated in 200 outpatients with pain after oral surgery. Under double-blind conditions SR high dose (2000 mg) or low dose (1000 mg), IR + SR high dose (500 + 1500 mg) or low dose (250 + 750 mg), or acetaminophen standard tablet high dose (1000 mg) or low dose (500 mg) were randomly administered after removal of a lower third molar. The hourly pain intensity was rated on a visual analog scale during 12 hours. The efficacy was based on peak effect (maximum pain intensity difference in percent), pain reduction (mean percentage pain intensity difference), duration of effect (time to remedication) and pain reduction index (pain reduction multiplied by duration of effect). Pain reduction was 37% with the 500-mg tablet and 54% with SR 2000 mg. The peak effect increased from 53% after 1.9 hours for the 500-mg tablet to 67% after 2.6 hours for SR 2000 mg. The SR formulation significantly increased the duration of effect without reduction in peak effect.

Secondary aortoenteric fistulas--an analysis of 42 cases.

Secondary aortoenteric fistulas are seen with an increasing frequency which parallels the expansion of reconstructive vascular surgery. During a 12-year period 42 cases have been collected from the hospitals, which perform most of the vascular surgery in Sweden (0.7% of vascular operations). Twenty-five were seen after operation for aortic aneurysm, 15 for aortoiliac occlusive disease, one after renal artery ligation (as a part of reconstruction for renovascular hypertension) and one after operation for an iliac pseudoaneurysm. The frequency of complications during and after the primary operation was high. The interval between operation and onset of fistula symptoms was significantly shorter if there had been infectious complications, the median interval was 32 months, the longest being 10 years. The most important symptom was gastrointestinal haemorrhage, consisting of several small bleeds often combined with septic complications. A large number of negative investigations usually preceded the final diagnosis which was made at exploratory laparotomy. After surgery for the fistula the frequency of complications and mortality, were very high. Mortality was 58%, the most common cause of death being a blow out of the aortic stump. Of those leaving hospital, several further operations were performed with a high mortality. Recurrence of the fistula occurred in 16 out of 34 patients who survived surgery. At follow-up (12-74 months after fistula closure) seven patients were still alive.

Significant of positive bacterial cultures from aortic aneurysms.

Samples for bacteriological examination were obtained from the aneurysm wall of 85 patients subjected to abdominal aortic aneurysmectomy. Twelve patients (14%) had positive cultures. A total of 13 bacterial strains were isolated, the majority of which were present in only small numbers and were regarded as contaminants. One patient developed a graft infection due to ischemic necrosis of the sigmoid colon. During the follow-up period no further graft infection was noted in patients with positive or negative aortic cultures. It is concluded that the aneurysm wall itself does not represent an important source of early or late graft infection.

Intraarterial and intraportal in vivo catheterization of the regenerating rat liver. Effects upon body and liver weights and DNA synthesis.

A method for concomitant partial hepatectomy and catheterization of the arterial and portal systems of the liver in the rat is described. Catheters were inserted into the gastroduodenal artery and the ileocolic vein. Continuous saline perfusion was performed during 36 hours. In catheterized rats recovery of liver and body weight lagged behind that of non-catheterized rats. The more extensive surgery and the presence of catheters also caused decreased incorporation of 3H-thymidine into liver DNA 24 hours postoperatively. The variation in thymidine incorporation between animals was large. It was shown that by pre-labelling liver DNA with 14C-thymidine the rats can serve as their own controls during acute experiments involving 3H-thymidine, thus reducing the inconsistency of individual variation.

Irradiation effects upon ischemic regenerating rat liver cells.

Starch particles injected into the arterial and portal systems of the liver of the rat caused a temporary blockage of the liver circulation and consequent hypoxia in the liver cells. In the regenerating liver this resulted in a 30-40% decrease of thymidine incorporation into DNA, when analysed 1.5 hours after injection. Irradiation-induced cell damage, evaluated by thymidine incorporation 1.5 hours after irradiation with a single dose of X-rays, was not ameliorated by the ischemic condition. It is suggested that this depends on an inhibited nucleotide metabolism and DNA synthesis leading to an additive metabolic hypoxic effect of the starch particles on radiation damage. An equal level of thymidine incorporation, however, was found in an ischemic and a non-ischemic group of animals 16 hours after irradiation. In this case the liver cells in the ischemic group had overcome the additional inhibition of DNA synthesis caused by temporary hypoxia.

The posterior approach for subfascial ligation of perforating veins.

A posterior midline incision was used for subfascial ligation of incompetent medial and lateral perforating veins in 57 limbs. The indications for surgery were recurrent ulceration in 41 limbs and severe skin changes in 16 limbs. At follow-up two years or more after surgery 48 limbs remained free from ulceration. Wound infection (7%) and necrosis (12%) healed with conservative treatment. In our experience the posterior approach is a good alternative to other methods for ligation of incompetent perforating veins in patients with advanced skin changes, including active ulceration.

Benign cementoblastoma--cementum analogue of benign osteoblastoma?

We believe that the current case is a good example of a "borderline lesion" that shows the histologic features of benign osteoblastoma but with some clinical features suggestive of a cementoblastoma, such as attachment to the roots. We suggest, however, that the involvement of the roots should not rule out the diagnosis of benign osteoblastoma. The fact that a benign osteoblastoma may envelop the roots in a way characteristic of a benign cementoblastoma, however, is suggestive of a close relationship between the two tumors.

A case of multiple arterial thromboses after oral contraceptives and ergotamine.

PIP: A 35-year-old previously healthy woman started using oral contraceptives in May 1965. In June ergotamine was prescribed for right temporal headaches. On November 4 she took 5 ergotamine tablets between 4-7 AM. By 9 AM she was confused and did not answer when spoken to. She was admitted to the hospital at 11 AM with an apoplexy picture. On November 6 carotid angiography on the right side showed a total occulsion of the internal carotid artery. An attempt at thrombectomy proved fruitless. In spite of intensive therapy, the patient died in cardiac arrest on the 3rd post operative day. Autopsy showed thrombotic masses in the right carotid artery and left ventricle. A contributory cause may have been the use of oral contraceptives in conjuction with ergotamine medication.^ieng