The Swiss National Registry for Primary Immunodeficiencies: report on the first 6 years' activity from 2008 to 2014.

The Swiss National Registry for Primary Immunodeficiency Disorders (PID) was established in 2008, constituting a nationwide network of paediatric and adult departments involved in the care of patients with PID at university medical centres, affiliated teaching hospitals and medical institutions. The registry collects anonymized clinical and genetic information on PID patients and is set up within the framework of the European database for PID, run by the European Society of Immunodeficiency Diseases. To date, a total of 348 patients are registered in Switzerland, indicating an estimated minimal prevalence of 4·2 patients per 100 000 inhabitants. Distribution of different PID categories, age and gender are similar to the European cohort of currently 19 091 registered patients: 'predominantly antibody disorders' are the most common diseases observed (n = 217/348, 62%), followed by 'phagocytic disorders' (n = 31/348, 9%). As expected, 'predominantly antibody disorders' are more prevalent in adults than in children (78 versus 31%). Within this category, 'common variable immunodeficiency disorder' (CVID) is the most prevalent PID (n = 98/217, 45%), followed by 'other hypogammaglobulinaemias' (i.e. a group of non-classified hypogammaglobulinaemias) (n = 54/217, 25%). Among 'phagocytic disorders', 'chronic granulomatous disease' is the most prevalent PID (n = 27/31, 87%). The diagnostic delay between onset of symptoms and diagnosis is high, with a median of 6 years for CVID and more than 3 years for 'other hypogammaglobulinaemias'.

Variability of fine particle dose and lung deposition of budesonide delivered through two multidose dry powder inhalers.

OBJECTIVE: To assess the reliability of dosing through two budesonide multidose dry powder inhalers (DPI) as derived from the in-vitro variability of the fine particle dose (FPD) and the in-vivo variability of the lung deposition at different flow rates. METHODS: The same two DPIs [device N (Novolizer) and device T (Turbuhaler)] were compared in both studies. In the in-vitro study, the variability of the FPD, measured at flow rates of 30-100 L/min, was determined for equal flow rates and at comparable maximal inspiratory pressures (MIP). In the in-vivo study in healthy subjects (scintigraphic, randomised, crossover design) the variability of the lung deposition was determined at targeted flow rates of 45, 60 and 90 L/min for device N, and at 60 L/min for device T. RESULTS: The variability of the FPD was lower with device N than with device T by 34%-86%. The differences were statistically significant for flow rates of 60, 70, 90 and 100 L/min (not significant for 40, 50 and 80 L/min) in the in-vitro study. Results for comparable MIPs showed analogous differences (79%, p = 0.004, at the clinically relevant MIP of 4.5 kPa). The variability of the lung deposition was clearly lower with the device N than with the device T. The difference was statistically significant (p = 0.029) at a comparable targeted flow rate of 60 L/min. CONCLUSIONS: Thus, this study showed that device N is likely to improve the reliability of inhalation therapy by reducing both the variability of the delivered drug and that of the lung deposition. The reliability of inhalation therapy and consequently the quality of long-term control of asthma and the patient's compliance might improve when choosing the DPI with the better characteristics.

Protruding aortic arch atheromas: risk of stroke during heart surgery with and without aortic arch endarterectomy.

BACKGROUND: Stroke occurs in 1% to 7% of heart surgery. Aortic arch atherosclerosis is a risk factor for intraoperative stroke, and endarterectomy has been proposed to prevent stroke during heart surgery in patients with arch atheromas. METHODS AND RESULTS: Intraoperative transesophageal echocardiography was performed in 3404 patients undergoing heart surgery between 1990 and 1996. Use of transesophageal echocardiography was unselected and based on equipment availability. Aortic arch atheromas (>/=5 mm, or mobile) were seen in 268 (8%) patients. They were evaluated for intraoperative stroke (confirmed by a neurologist and cerebral infarction on computed tomography or magnetic resonance imaging). Arch endarterectomy was performed in 43 patients as an adjunct to their cardiac procedure in an attempt to prevent intraoperative stroke. The intraoperative stroke rate in all 268 patients with atheromas was high (15.3%). On univariate analysis, age, previous stroke, and arch endarterectomy were significantly associated with intraoperative stroke. On multivariate analysis, age (odds ratio 3.9, P =.01) and arch endarterectomy (odds ratio 3.6, P =.001) were independently predictive of intraoperative stroke. Mortality rate in all 268 patients was high (14.9%). These patients with atheromas also had a long recovery room, intensive care unit, and total hospital length of stay (48 days). CONCLUSIONS: Patients with protruding aortic arch atheromas are at high risk for intraoperative stroke, significant and multiple morbidity, prolonged hospital stay, and death resulting from heart surgery. Aortic arch endarterectomy is strongly associated with intraoperative stroke; its use should be carefully considered in light of these results.

Cerebral injury after cardiac surgery: identification of a group at extraordinary risk. Multicenter Study of Perioperative Ischemia Research Group (McSPI) and the Ischemia Research Education Foundation (IREF) Investigators.

BACKGROUND AND PURPOSE: Cerebral injury after cardiac surgery is now recognized as a serious and costly healthcare problem mandating immediate attention. To effect solution, those subgroups of patients at greatest risk must be identified, thereby allowing efficient implementation of new clinical strategies. No such subgroup has been identified; however, patients undergoing intracardiac surgery are thought to be at high risk, but comprehensive data regarding specific risk, impact on cost, and discharge disposition are not available. METHODS: We prospectively studied 273 patients enrolled from 24 diverse US medical centers, who were undergoing intracardiac and coronary artery surgery. Patient data were collected using standardized methods and included clinical, historical, specialized testing, neurological outcome and autopsy data, and measures of resource utilization. Adverse outcomes were defined a priori and determined after database closure by a blinded independent panel. Stepwise logistic regression models were developed to estimate the relative risks associated with clinical history and intraoperative and postoperative events. RESULTS: Adverse cerebral outcomes occurred in 16% of patients (43/273), being nearly equally divided between type I outcomes (8.4%; 5 cerebral deaths, 16 nonfatal strokes, and 2 new TIAs) and type II outcomes (7.3%; 17 new intellectual deterioration persisting at hospital discharge and 3 newly diagnosed seizures). Associated resource utilization was significantly increased--prolonging median intensive care unit stay from 3 days (no adverse cerebral outcome) to 8 days (type I; P<0.001) and from 3 to 6 days (type II; P<0.001), and increasing hospitalization by 50% (type II, P=0.04) to 100% (type I, P<0.001). Furthermore, specialized care after hospital discharge was frequently necessary in those with type I outcomes, in that only 31% returned home compared with 85% of patients without cerebral complications (P<0.001). Significant risk factors for type I outcomes related primarily to embolic phenomena, including proximal aortic atherosclerosis, intracardiac thrombus, and intermittent clamping of the aorta during surgery. For type II outcomes, risk factors again included proximal aortic atherosclerosis, as well as a preoperative history of endocarditis, alcohol abuse, perioperative dysrhythmia or poorly controlled hypertension, and the development of a low-output state after cardiopulmonary bypass. CONCLUSIONS: These prospective multicenter findings demonstrate that patients undergoing intracardiac surgery combined with coronary revascularization are at formidable risk, in that 1 in 6 will develop cerebral complications that are frequently costly and devastating. Thus, new strategies for perioperative management--including technical and pharmacological interventions--are now mandated for this subgroup of cardiac surgery patients.

Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators.

BACKGROUND: Acute changes in cerebral function after elective coronary bypass surgery is a difficult clinical problem. We carried out a multicenter study to determine the incidence and predictors of -- and the use of resources associated with -- perioperative adverse neurologic events, including cerebral injury. METHODS: In a prospective study, we evaluated 2108 patients from 24 U.S. institutions for two general categories of neurologic outcome: type I (focal injury, or stupor or coma at discharge) and type II (deterioration in intellectual function, memory deficit, or seizures). RESULTS: Adverse cerebral outcomes occurred in 129 patients (6.1 percent). A total of 3.1 percent had type I neurologic outcomes (8 died of cerebral injury, 55 had nonfatal strokes, 2 had transient ischemic attacks, and 1 had stupor), and 3.0 percent had type II outcomes (55 had deterioration of intellectual function and 8 had seizures). Patients with adverse cerebral outcomes had higher in-hospital mortality (21 percent of patients with type I outcomes died, vs. 10 percent of those with type II and 2 percent of those with no adverse cerebral outcome; P<0.001 for all comparisons), longer hospitalization (25 days with type I outcomes, 21 days with type II, and 10 days with no adverse outcome; P<0.001), and a higher rate of discharge to facilities for intermediate- or long-term care (69 percent, 39 percent, and 10 percent ; P<0.001). Predictors of type I outcomes were proximal aortic atherosclerosis, a history of neurologic disease, and older age; predictors of type II outcomes were older age, systolic hypertension on admission, pulmonary disease, and excessive consumption of alcohol. CONCLUSIONS: Adverse cerebral outcomes after coronary bypass surgery are relatively common and serious; they are associated with substantial increases in mortality, length of hospitalization, and use of intermediate- or long-term care facilities. New diagnostic and therapeutic strategies must be developed to lessen such injury.

Multicenter preoperative stroke risk index for patients undergoing coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

BACKGROUND: The paradox of present cardiac surgery is that the more elderly and debilitated patients benefit most from cardiac surgery compared with medical therapy, yet they sustain greater overall risk for morbidity and mortality after cardiac surgery. The goal of the present study was to develop a preoperative index predicting major perioperative neurological events in patients undergoing coronary artery bypass graft surgery. METHODS AND RESULTS: As part of a prospective, multicenter, observational study (McSPI Research Group), we enrolled 2417 patients at 24 academic medical centers in the United States. Patients who died intraoperatively or had concomitant open-heart procedures were excluded from analysis, resulting in a total of 2107 for analysis. Sixty-eight patients (3.2%) developed adverse neurological events, defined as cerebrovascular accident, transient ischemic attack (TIA), or persistent coma. Bivariate analysis was applied to determine associations between preoperative variables and neurological events. Significant bivariate predictors were identified then logically grouped, and for each cluster, a score was calculated based on principal components. Key predictor variables were age, history of previous neurological disease, diabetes, history of vascular disease, previous coronary artery surgery, unstable angina, and history of pulmonary disease, the coefficients for which were used to develop a preoperative stroke risk index that was validated by bootstrap (c-index = 0.778). Stroke risk could then be determined for each patient, calculating a patient's risk for stroke within 95% confidence intervals. CONCLUSIONS: With the McSPI stroke risk index developed in this study, neurological risk can be estimated, and the most appropriate group for perioperative therapy can be identified. Further refinement and validation of this index, however, are necessary and are under way in current studies.

Effect of cannula length on aortic arch flow: protection of the atheromatous aortic arch.

Atheromatous disease in the transverse aortic arch is associated with an increased incidence of perioperative stroke. In addition, tissue erosion in the aortic arch is caused by the high-velocity jet emerging from an aortic cannula during cardiopulmonary bypass (CPB), termed the "sandblast effect". To quantify this phenomenon, flow in the aortic arch was measured intraoperatively by epiaortic ultrasonography in 18 patients undergoing CPB. All were cannulated in the ascending aorta, 10 with a short (1.5 cm) cannula and 8 with a long (7.0 cm) cannula. The peak forward aortic flow velocities (mean +/- standard deviation) measured on the caudal luminal surface of the aortic arch were 0.80 +/- 0.23 m/s off CPB and 2.42 +/- 0.69 m/s on CPB (p < 0.001) for the short cannula and 0.53 +/- 0.20 m/s off CPB and 0.18 m/s on CPB for the long cannula. Thus, during CPB the peak forward aortic flow velocity with the short cannula was significantly greater (p < 0.001) than before CPB, whereas the long cannula produced a lower peak forward aortic flow velocity during CPB. Furthermore, Doppler examination revealed severe turbulence in the aortic arch in all patients with a short cannula. No arch turbulence, however, was seen in 7 patients with a long cannula, and only mild turbulence appeared in the remaining patient with a long cannula. These results show that use of a long aortic cannula results in a significant decrease in peak forward aortic flow velocity and turbulence in the aortic arch during CPB, which may reduce the risk of erosion or disruption of existing atheroma and ensuing embolic complications.

Superiority of transesophageal echocardiography in detecting aortic arch atheromatous disease: identification of patients at increased risk of stroke during cardiac surgery.

It has been shown that transesophageal echocardiography (TEE) is useful in evaluating atheromatous disease of the aortic arch and that such disease is a risk factor for stroke in medical patients. Data obtained by traditional methods of evaluating the aortic arch prior to cardiac surgery, namely, chest x-ray (CXR) and cardiac catheterization (CATH), were compared with that detected by TEE. Images of the descending thoracic aorta and aortic arch seen on intraoperative TEE in 258 cardiac surgical patients were graded as I = normal, II = intimal thickening or plaques < 5 mm thick or with a mobile component (severe disease). The aortic knob seen on CXR in 209 of these patients was graded as normal, < 1/2 or > or = > 1/2 ring of calcification. Calcification in the aortic root (graded as 0, 1+, 2+) and irregularities in the aortic lumen seen at CATH in 33 patients were also examined. Data were analyzed with respect to age, gender, type of surgery, and stroke. Increasing age correlated strongly with increasing severity of aortic arch and descending thoracic aortic disease seen by TEE. Severe disease was not present in patients under age 50 but was present in about 20% of those over age 70. Atheromatous disease was found by TEE in 55% of patients with a normal CXR and 91% of those with heavily calcified aortic knobs. Ischemic strokes occurred in seven patients. Severe arch disease correlated significantly with stroke (P < .01). Other variables did not correlate with stroke.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-endorphin and ACTH levels in the perioperative period.

1. The purpose of this study was to determine the plasma levels of beta-endorphin (beta-END) and ACTH in the perioperative period, define correlations of hormonal plasma levels with clinical parameters and establish the effect of droperidol premedication on hormonal levels and clinical parameters. 2. Twenty two were assigned to one of two groups: (1) Control (no premedication) and (2) droperidol (7.5 mg im) premedication. 3. Venous blood samples and clinical evaluations were done the day prior to surgery, just prior to induction of anesthesia and 1-1.5 hr postoperatively. 4. The results indicate that (1) expectancy of surgery on arrival to the operating room increases beta-END but not ACTH plasma levels, (2) this increase in beta-END is not affected by droperidol administration and (3) postsurgical stress increases beta-END and ACTH above operating room levels. 5. These results indicate that although beta-END and ACTH are both produced by the pituitary and derived from a common precursor, the type of stimuli (pre- versus postsurgical stress) seems to differentially affect their plasma levels.

The value of routine daily chest x-rays in intubated patients in the medical intensive care unit.

Two hundred routine chest x-rays were evaluated to determine their value in the management of critically ill patients in a Medical ICU (MICU). Seventy-four x-rays (37%) were of suboptimal value or were delivered to the MICU too late for inclusion on morning rounds. Of the remaining 126 films, 54 (43%) showed worsening of a known, or development of a new, cardiopulmonary abnormality, or an unexpected misplacement of an invasive device. On the basis of these findings, routine daily chest radiographs were judged to be valuable in identifying abnormalities in critically ill patients. However, the system for providing this service was only 63% efficient, and improvement must be sought in this regard.