Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study.

BACKGROUND: Neutropenia, defined as an absolute blood neutrophil count (ANC) <1.5 G L(-1) , may accompany a variety of diseases. However, the clinical significance of neutropenia detected in a routine complete blood cell count is poorly understood. METHODS: Using a primary care resource, comprising more than 370 000 individuals, we assessed the association with a number of previously recognized conditions as well as all-cause mortality in the 4 years following the identification of neutropenia. By matching laboratory data with Danish nationwide health registers, risk estimates were assessed. RESULTS: Neutropenia was observed in approximately 1% of all individuals and was associated dose dependently with viral infections, haematological malignancies (but not autoimmune disorders or solid cancers) and mortality. Neutropenia was particularly associated with HIV, acute leukaemias and myelodysplastic syndromes. Odds ratios [95% confidence interval (CI)] for viral infections were 2.32 (1.84-2.91), 2.80 (2.20-3.57) and 4.77 (3.22-7.07) for subnormal (≥1.5-1.8 G L(-1) ), mild (≥1.0-1.5 G L(-1) ) and moderate-severe (≥0.0-1.0 G L(-1) ) neutropenic individuals, respectively (all P < 0.001). Likewise, odds ratios (95% CI) for haematological malignancies were 3.23 (2.35-4.45), 8.69 (6.58-11.47) and 46.03 (33.98-62.35 ), for the same neutropenia levels, respectively (all P < 0.001). Thus, the lower the ANC, the greater the likelihood of these diseases. The relative risk estimates observed for severe neutropenia corresponded to absolute risks of haematological malignancies and mortality from any cause of 40% and >50%, respectively. CONCLUSIONS: Neutropenia is an ominous sign necessitating careful follow-up. The risk estimates presented here support focusing attention to viral diseases and haematological malignancies when neutropenia is observed.

The role of the anterolateral ligament in ACL insufficient and reconstructed knees on rotatory stability: A biomechanical study on human cadavers.

Studies suggest that the anterolateral ligament (ALL) is important for knee stability. The purpose was to clarify ALL's effect on rotatory and anterior-posterior stability in the anterior cruciate ligament (ACL)-insufficient and reconstructed knees and the effect of reconstruction of an insufficient ALL. Eighteen cadaveric knees were included. Stability was tested for intact (+ALL), detached (-ALL) and reconstructed (+ reALL) ALL, with ACL removed (-ACL) and reconstructed (+ACL) in six combinations. All were tested in 0, 30, 60, and 90 °C flexion. Anterior-posterior stability was measured with a rolimeter. Rotation with a torque of 8.85 Nm was measured photographically. The ALL was well defined in 78% of knees. ACL reconstruction had a significant effect on anterior-posterior stability. Detaching the ALL had a significant effect on internal rotatory stability and on anterior-posterior stability in ACL-insufficient knees. Reconstruction of ACL and ALL reestablished knee stability. The appearance of the ALL was not uniform. The ALL was an internal rotational stabilizer. Anatomical ALL reconstruction in combination with ACL reconstruction could reestablish stability. ALL reconstruction might be considered in patients with combined ACL and ALL tears, but the clinical effect should be established in a controlled clinical study.

Risk of new or recurrent cancer after a high perioperative inspiratory oxygen fraction during abdominal surgery.

BACKGROUND: Administration of supplemental oxygen in the perioperative period is controversial, as it may increase long-term mortality. Our aim was to assess the association between 80% oxygen and occurrence of subsequent cancer in patients undergoing abdominal surgery in a post hoc analysis of the PROXI trial. METHODS: The 1386 patients in the PROXI trial underwent elective or emergency laparotomy between 2006 and 2008 with randomization to either 80% or 30% oxygen during and for 2 h after surgery. We retrieved follow-up status regarding vital status, new cancer diagnoses, and new histological cancer specimens. Data were analysed using the Cox proportional hazards model. RESULTS: Follow-up was complete in 1377 patients (99%) after a median of 3.9 yr. The primary outcome of new cancer diagnosis or new malignant histological specimen occurred in 140 of 678 patients (21%) in the 80% oxygen group vs 150 of 699 patients (21%) assigned to 30% oxygen; hazards ratio 1.06 [95% confidence interval (CI) 0.84, 1.34], P=0.62. Cancer-free survival was significantly shorter in the 80% oxygen group; hazards ratio 1.19 (95% CI 1.01, 1.42), P=0.04, as was the time between surgery and new cancer, median 335 vs. 434 days in the 30% oxygen group. In patients with localized disease, non-significant differences in cancer and cancer-free survival were found with hazard ratios of 1.31 and 1.29, respectively. CONCLUSIONS: Although new cancers occurred at similar rate, the cancer-free survival was significantly shorter in the 80% oxygen group, but this did not appear to explain the excess mortality in the 80% oxygen group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01723280).

Is peri-operative cortisol secretion related to post-operative cognitive dysfunction?

BACKGROUND: The pattern of cortisol secretion is influenced by surgery. As cortisol can adversely affect neuronal function, this may be an important factor in the development of post-operative cognitive dysfunction (POCD). We hypothesized that the incidence of POCD would be related to changes in cortisol level. METHODS: We studied 187 patients aged over 60 years undergoing major non-cardiac surgery with general or regional anaesthesia. Saliva cortisol levels were measured pre-operatively and at 1 day, 7 days and 3 months post-operatively in the morning (08.00 h) and in the afternoon (16.00 h) using salivettes. Cognitive function was assessed pre-operatively, on day 7 and at 3 months using four neuropsychological tests. POCD was defined as a combined Z score of greater than 1.96. RESULTS: After surgery, salivary cortisol concentrations increased significantly. POCD was detected in 18.8% of subjects at 1 week and in 15.2% after 3 months. The pre-operative ratios between the morning and afternoon cortisol concentrations (am/pm ratios) were 2.8 and 2.7 in patients with POCD at 1 week vs. those without POCD at 1 week, respectively. The am/pm ratios decreased significantly post-operatively to 1.9 and 1.6 at 1 week, respectively (P = 0.02 for both). In an analysis considering all am/pm ratios, it was found that the persistent flattening in am/pm ratio was significantly related to POCD at 1 week. CONCLUSION: The pattern of diurnal variation in cortisol level was significantly related to POCD. Thus, circadian rhythm disturbance or metabolic endocrine stress could be an important mechanism in the development of cognitive dysfunction after major surgery.

Postoperative cognitive dysfunction: true deterioration versus random variation.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication, especially in the elderly. The aim of this study was to describe how variability in neuropsychological testing could lead to the detection of cognitive improvement and poor consistency of POCD between postoperative test sessions. METHODS: In four published studies performed by the ISPOCD group, we included 2536 patients and 359 healthy controls. Cognitive function was assessed using neuropsychological tests preoperatively and at 7 days and 3 months thereafter, comparing the changes between those at baseline with those after surgery. Postoperative cognitive dysfunction was defined as a Z score greater than 2, and we also defined a corresponding improvement as a Z score less than -2. Consistency of POCD between postoperative test sessions was analyzed and we also assessed test-retest variability using data from healthy control subjects. RESULTS: Improvement in cognitive function was found in 4.2-8.7% of patients after 1 week and in 5.0-7.8% after 3 months. The ratio between incidence of dysfunction and improvement varied in patients between 3.3 and 6.2 early after major surgery. Of those patients who displayed POCD at the 3-month test, 30-48% also had POCD at the previous test at 1 week. The test-retest reliability was between 0.56 and 0.90, except for the error score in Concept Shifting Test, where the values were 0.20 and 0.37. CONCLUSION: Variability in neuropsychological test data contributes to a low consistency between postoperative test sessions but it does not explain the detection of cognitive dysfunction after major surgery.

Cognitive dysfunction after minor surgery in the elderly.

BACKGROUND: Major surgery is frequently associated with postoperative cognitive dysfunction (POCD) in elderly patients. Type of surgery and hospitalization may be important prognostic factors. The aims of the study were to find the incidence and risk factors for POCD in elderly patients undergoing minor surgery. METHODS: We enrolled 372 patients aged greater than 60 years scheduled for minor surgery under general anesthesia. According to local practice, patients were allocated to either in- (199) or out-patient (173) care. Cognitive function was assessed using neuropsychological testing preoperatively and 7 days and 3 months postoperatively. Postoperative cognitive dysfunction was defined using Z-score analysis. RESULTS: At 7 days, the incidence (confidence interval) of POCD in patients undergoing minor surgery was 6.8% (4.3-10.1). At 3 months the incidence of POCD was 6.6% (4.1-10.0). Logistic regression analysis identified the following significant risk factors: age greater than 70 years (odds ratio [OR]: 3.8 [1.7-8.7], P = 0.01) and in- vs. out-patient surgery (OR: 2.8 [1.2-6.3], P = 0.04). CONCLUSIONS: Our finding of less cognitive dysfunction in the first postoperative week in elderly patients undergoing minor surgery on an out-patient basis supports a strategy of avoiding hospitalization of older patients when possible.

Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac and major non-cardiac surgery with general anaesthesia in the elderly. We hypothesized that the incidence of POCD would be less with regional anaesthesia rather than general. METHODS: We included patients aged over 60 years undergoing major non-cardiac surgery. After giving written informed consent, patients were randomly allocated to general or regional anaesthesia. Cognitive function was assessed using four neuropsychological tests undertaken preoperatively and at 7 days and 3 months postoperatively. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in two or more test parameters. RESULTS: At 7 days, POCD was found in 37/188 patients (19.7%, [14.3-26.1%]) after general anaesthesia and in 22/176 (12.5%, [8.0-18.3%]) after regional anaesthesia, P = 0.06. After 3 months, POCD was present in 25/175 patients (14.3%, [9.5-20.4%]) after general anaesthesia vs. 23/165 (13.9%, [9.0-20.2%]) after regional anaesthesia, P = 0.93. The incidence of POCD after 1 week was significantly greater after general anaesthesia when we excluded patients who did not receive the allocated anaesthetic: 33/156 (21.2%[15.0-28.4%]) vs. 20/158 (12.7%[7.9-18.9%]) (P = 0.04). Mortality was significantly greater after general anaesthesia (4/217 vs. 0/211 (P < 0.05)). CONCLUSION: No significant difference was found in the incidence of cognitive dysfunction 3 months after either general or regional anaesthesia in elderly patients. Thus, there seems to be no causative relationship between general anaesthesia and long-term POCD. Regional anaesthesia may decrease mortality and the incidence of POCD early after surgery.