The effect of postoperative intravenous iron in anaemic, older cardiac surgery patients on disability-free survival (AGE ANEMIA study): study protocol for a multi-centre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Postoperative anaemia is common in older cardiac surgery patients and often caused by iron deficiency. Anaemia may negatively affect recovery after cardiac surgery. This study aims to determine the efficacy of treatment of postoperative iron deficiency anaemia (IDA) with intravenous iron (IVI) on disability 90 days after cardiac surgery in older patients. METHODS: This is a randomized placebo-controlled double-blind multi-centre trial. In total, 310 patients aged ≥ 70 years with moderate IDA on postoperative day 1 (haemoglobin 85-110 g/L and ferritin concentration < 100 µg/L or iron saturation < 20%) after uncomplicated elective cardiac surgery (aortic valve repair or coronary artery bypass graft surgery) will be included. Patients will be randomly allocated to receive either IVI (ferric derisomaltose) or placebo (sodium chloride 0.9%) on postoperative day 1 in a 1:1 ratio, stratified by centre and type of cardiac surgery. The primary outcome is disability measured by the 12-item World Health Organization Disability Assessment score 2.0 after 90 days. Secondary outcome measures are the number of postoperative red blood cell (RBC) transfusions, change in reticulocyte haemoglobin content (pg) from randomization to hospital discharge, Hb levels at discharge, hospital complications, dyspnoea (assessed with the Rose Dyspnoea Scale) and health-related quality of life (HRQL) (assessed with The Older Persons and Informal Caregivers-Short Form (TOPICS-SF) questionnaire) after 90 days and days alive and out of hospital after 90 days. Lastly, the functional outcomes (e.g. steep ramp or 6-min walk test) and Hb level after 90 days will be assessed as an exploratory endpoint. DISCUSSION: The results of this study will demonstrate whether early treatment of postoperative IDA with IVI improves disability at 90 days in older cardiac surgery patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04913649. Registered on June 4, 2021.

Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

Chlamydiae in febrile children with respiratory tract symptoms and age-matched controls, Ghana.

Members of the Chlamydiales order are obligate intracellular pathogens causing acute and chronic infectious diseases. Chlamydiaceae are established agents of community- and zoonotically acquired respiratory tract infections, and emerging pathogens among the Chlamydia-related bacteria have been implicated in airway infections. The role of both in airway infections in Africa is underexplored. We performed a case -control study on the prevalence of Chlamydiaceae and Chlamydia-related emerging pathogens in children with febrile respiratory tract infections in West Africa, Ghana. Using a pan-Chlamydiales broad-range real-time PCR, we detected chlamydial DNA in 11 (1.9%) of 572 hospitalized febrile children with respiratory tract symptoms and in 24 (4.3%) of 560 asymptomatic age-matched controls (p 0.03). Chlamydiaceae were found to be common among both symptomatic and healthy Ghanaian children, with Chlamydia pneumoniae being the most prevalent species. Parachlamydiaceae were detected in two children without symptoms but not in the symptomatic group. We identified neither Chlamydia psittaci nor Simkania negevensis but a member of a new chlamydial family that shared 90.2% sequence identity with the 16S rRNA gene of the zoonotic pathogen Chlamydia pecorum. In addition, we found a new Chlamydia-related species that belonged to a novel family sharing 91.3% 16S rRNA sequence identity with Candidatus Syngnamydia venezia. The prevalence and spectrum of chlamydial species differed from previous results obtained from children of other geographic regions and our study indicates that both, Chlamydiaceae and Chlamydia-related bacteria, are not clearly linked to clinical symptoms in Ghanaian children.

High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery.

BACKGROUND: Postoperative non-cardiac complication rates are as high as 11-28% after high-risk abdominal procedures. Emerging evidence indicates that postoperative cardiac troponin T elevations are associated with adverse outcome in non-cardiac surgery. The aim of this study was to determine the relationship between postoperative high-sensitive cardiac troponin T elevations and non-cardiac complications in patients after major abdominal surgery. METHODS: This prospective observational single-centre cohort study included patients at risk for coronary artery disease undergoing elective major abdominal surgery. Cardiac troponin was measured before surgery and at day 1, 3, and 7. Multivariable logistic regression analysis was performed to examine the adjusted association for different cut-off concentrations of postoperative myocardial injury and non-cardiac outcome. RESULTS: In 203 patients, 690 high-sensitive cardiac troponin T measurements were performed. Fifty-three patients (26%) had a non-cardiac complication within 30 days after surgery. Hospital mortality was 4% (8/203). An increase in cardiac troponin T concentration ≥100% compared with baseline was a superior independent predictor of non-cardiac postoperative clinical complications (adjusted odds ratio 4.3, 95% confidence interval 1.8-10.1, P<0.001) and was associated with increased length of stay (9 days, 95% confidence interval 7-11 vs 7 days, 95% confidence interval 6-8, P=0.004) and increased hospital mortality (12 vs 2%, P=0.028). CONCLUSIONS: A postoperative high-sensitive cardiac troponin T increase ≥100% is a strong predictor of non-cardiac 30 day complications, increased hospital stay and hospital mortality in patients undergoing major abdominal surgery. CLINICALTRIALSGOV IDENTIFIER: NCT02150486.

Preoperative statin therapy and infectious complications in cardiac surgery.

AIM: To assess whether preoperative statin therapy is associated with the risk of postoperative infection in patients undergoing cardiac surgery. METHODS: 520 patients undergoing cardiac surgery in 2010 were retrospectively examined. Data regarding statin and antibiotic use prior to and after surgery were available from the hospital pharmacy information system. Cultures and clinical data of patients on postoperative antibiotics other than standard prophylactic therapy were studied to identify postoperative infections up to 30 days from day of surgery. RESULTS: 370 (71.2 %) patients were on preoperative statin therapy. Overall, 82 patients (15.8 %) suffered from postoperative infection of which 11 were surgical site infections. In multivariable regression analysis, statin therapy was associated with a reduced risk of postoperative infection (adjusted odds ratio: 0.329, 95 %: CI 0.19-0.57; P < 0.001). CONCLUSIONS: Preoperative statin use was associated with a considerable reduced risk of postoperative infections following cardiac surgery. Randomised controlled trials are required to clarify the role of statin therapy in the prevention of postoperative infections.

Prognostic significance of biochemical markers in African Burkitt's lymphoma.

BACKGROUND AND PURPOSE Endemic Burkitt's lymphoma (eBL) remains the prevalent form of paediatric cancer in tropical Africa with subtle pathological differences. This calls for intensified efforts to validate the global prognostic markers within local settings for improved cancer treatment and survival. This study proposes prognostic markers for enhanced eBL treatment and management. PATIENTS AND METHOD One hundred and eighty histologically and/or clinically diagnosed BL patients at Komfo Anokye Teaching Hospital, Kumasi, Ghana were eligible for this cross-sectional eight-year retrospective study. Biochemical, clinical and demographic data, before chemotherapy administration, were documented and examined for their progression-free (PFS) and overall survival (OS) significance. RESULTS A mean age of 6 (SD=2.7, range: 1-16) years was observed with general male dominance (M:F=1.69:1). Total serum lactate dehydrogenase (HR=2.04; 95% CI, 1.25-3.32; log rank=8.3; p=0.004), serum creatinine (HR=3.59; 95% CI, 1.62-7.98; log rank=15.4; p=0.002) and St. Jude stage (HR=1.74; 95% CI, 1.11-2.73; log rank=8.0; p=0.015) were important independent prognostic biochemical markers for both PFS and OS. Age, serum calcium, uric acid, potassium, sodium and phosphorus were non-prognostic. CONCLUSION The better monitoring of these prognostic indices coupled with risk-stratification treatment may improve patients' survival, especially in resource-limited settings.

Prognostic significance of biochemical markers in African Burkitt's lymphoma

BACKGROUND AND PURPOSE Endemic Burkitt's lymphoma (eBL) remains the prevalent form of paediatric cancer in tropical Africa with subtle pathological differences. This calls for intensified efforts to validate the global prognostic markers within local settings for improved cancer treatment and survival. This study proposes prognostic markers for enhanced eBL treatment and management. PATIENTS AND METHOD One hundred and eighty histologically and/or clinically diagnosed BL patients at Komfo Anokye Teaching Hospital, Kumasi, Ghana were eligible for this cross-sectional eight-year retrospective study. Biochemical, clinical and demographic data, before chemotherapy administration, were documented and examined for their progression-free (PFS) and overall survival (OS) significance. RESULTS A mean age of 6 (SD=2.7, range: 1-16) years was observed with general male dominance (M:F=1.69:1). Total serum lactate dehydrogenase (HR=2.04; 95% CI, 1.25-3.32; log rank=8.3; p=0.004), serum creatinine (HR=3.59; 95% CI, 1.62-7.98; log rank=15.4; p=0.002) and St. Jude stage (HR=1.74; 95% CI, 1.11-2.73; log rank=8.0; p=0.015) were important independent prognostic biochemical markers for both PFS and OS. Age, serum calcium, uric acid, potassium, sodium and phosphorus were non-prognostic. CONCLUSION The better monitoring of these prognostic indices coupled with risk-stratification treatment may improve patients' survival, especially in resource-limited settings (AU)

Clinical and epidemiological characterisation of Burkitt's lymphoma: an eight-year case study at Komfo Anokye Teaching Hospital, Ghana.

Endemic Burkitt's lymphoma (BL) is a juvenile malignant neoplasm of B-lymphocyte origin, markedly affected by climate, vegetation and geographical location. This real country-based, cross-sectional, retrospective study reviews all out-patient clinical records of patients histologically and/or clinically diagnosed with BL from January, 2000 to December, 2007 at the Komfo Anokye Teaching Hospital, Ghana, a country within the malaria and lymphoma belts of the world. The aim of the study is to clinically and epidemiologically characterise all cases of BL over an eight-year period to ascertain the most common form of BL demographically prevalent. A mean age of 6.9 +/- 2.7 (range: 1-16) was observed. Males generally dominated in incidence (M:F=1.43:1, P<0.001) and significantly with facial presentation (P<0.05). Females weakly dominated in abdominal tumour presentation (P>0.05). The age range 4-8 years was the high risk range (P<0.001) for both sexes. Males were affected early in life (4-7 years) compared to their female counterparts (6-11 years). Of the 551 cases reviewed, 48.3%, 32.7%, 15.8% and 3.3% involved the face, abdomen, combined facial and abdominal and either facial or abdominal with central nervous system (CNS) involvement (usually paraplegia), respectively. An intriguing observation was evident between facial and combined facial and abdominal cases which exhibited reversed trends in incidence. Three regions within the forest zone showed significantly higher (P<0.001) incidences compared to the seven cohorts from the coastal and savannah agro-ecological zones of Ghana. No region was explicitly associated with any particular clinical presentation. The study has shown that although BL can present with demographic patterns in prevalence within a given geographical location, no clinical characterisation is associated with such patterns.

Influence of transoesophageal echocardiography on therapy and prognosis in young patients with TIA or ischaemic stroke.

Objective. To determine the influence of transoesophageal echocardiography (TEE) on therapy and prognosis in patients with cryptogenic transient ischaemic attack (TIA) or ischaemic stroke under the age of 50 years.Methods and results. We evaluated all patients aged 50 and under who were referred to our university hospital for cryptogenic TIA or ischaemic stroke during the period 1 January 1996 to 31 December 2004. All patients underwent both transthoracic echocardiography (TTE) and TEE. Patients with known pre-existent heart disease, such as atrial fibrillation, were excluded. Eighty-three patients with TIA (22) and ischaemic stroke (61) were enrolled. Mean age was 39+/-8 years (range 18 to 50). In 30% of the patients TEE detected one or more potential cardioembolic source, compared with 10% for TTE (p=0.003). Standard treatment (aspirin 38 mg daily) was changed in 7% of the patients due to the TEE findings. Complete followup was obtained in 93% with an average of 5+/-3 years. Twelve recurrences occurred; two out of six patients (33%) with therapy change and ten out of 71 (14%) of the patients without therapy change had a recurrent TIA or ischaemic Stroke.Conclusion. In patients with cryptogenic TIA or ischaemic stroke, TEE is superior to TTE in the detection of a potential cardiac source of embolism. However, findings obtained by TEE only influence the already initiated treatment in a small percentage of patients. The recurrence rate both in the group with and without therapy change is high. (Neth Heart J 2009;17:373-7.).

1998 SM165: a large Kuiper belt object with an irregular shape.

The recent discovery of an ancient reservoir of icy bodies at and beyond the orbit of Neptune-the Kuiper belt-has opened a new frontier in astronomy. Measurements of the physical and chemical nature of Kuiper belt objects (KBOs) can constrain our ideas of the processes of planet formation and evolution. Our 1.8-m Vatican Advanced Technology Telescope and charge-coupled device camera observations of the KBO 1998 SM(165) indicate its brightness periodically varies by 0.56 magnitudes over a 4-h interval. If we assume a uniform albedo of 0.04, which is typical of values found in the literature for a handful of KBOs, and an "equator-on" aspect, we find 1998 SM(165) has axes of length 600 x 360 km. If our assumptions are correct, such dimensions put 1998 SM(165) among the largest elongated objects known in our solar system. Perhaps long ago, two nearly spherical KBOs of comparable size coalesced to form a compound object, or perhaps 1998 SM(165) is the residual core of a catastrophic fragmentation of a larger precursor.

Organic composition of C/1999 S4 (LINEAR): a comet formed near Jupiter?

In the current paradigm, Oort cloud comets formed in the giant planets' region of the solar nebula, where temperatures and other conditions varied greatly. The measured compositions of four such comets (Halley, Hyakutake, Hale-Bopp, and Lee) are consistent with formation from interstellar ices in the cold nebular region beyond Uranus. The composition of comet C/1999 S4 (LINEAR) differs greatly, which suggests that its ices condensed from processed nebular gas, probably in the Jupiter-Saturn region. Its unusual organic composition may require reevaluation of the prebiotic organic material delivered to the young Earth by comets.

Identification of two sources of carbon monoxide in comet Hale-Bopp.

The composition of ices in comets may reflect that of the molecular cloud in which the Sun formed, or it may show evidence of chemical processing in the pre-planetary accretion disk around the proto-Sun. As carbon monoxide (CO) is ubiquitous in molecular clouds, its abundance with respect to water could help to determine the degree to which pre-cometary material was processed, although variations in CO abundance may also be influenced by the distance from the Sun at which comets formed. Observations have not hitherto provided an unambiguous measure of CO in the cometary ice (native CO). Evidence for an extended source of CO associated with comet Halley was provided by the Giotto spacecraft, but alternative interpretations exist. Here we report observations of comet Hale-Bopp which show that about half of the CO in the comet comes directly from ice stored in the nucleus. The abundance of this CO with respect to water (12 per cent) is smaller than in quiescent regions of molecular clouds, but is consistent with that measured in proto-stellar envelopes, suggesting that the ices underwent some processing before their inclusion into Hale-Bopp. The remaining CO arises in the coma, probably through thermal destruction of more complex molecules.

Detection of the 2165 inverse centimeter (4.619 micron) XCN band in the spectrum of L1551 IRS 5.

We report the detection of a broad absorption band at 2165 cm-1 (4.619 microns) in the spectrum of L1551 IRS 5. New laboratory results over the 2200-2100 cm-1 wavenumber interval (4.55-4.76 microns), performed with realistic interstellar ice analogs, suggest that this feature is due to a CN-containing compound. We will refer to this compound as XCN. We also confirm the presence of frozen CO (both in nonpolar and polar matrices) through absorption bands at 2140 cm-1 (4.67 microns) and 2135 cm-1 (4.68 microns). The relative abundance of solid-state CO to frozen H2O is approximately 0.13 while the abundance of XCN seems comparable to that of frozen CO.

Structure of the sensory innervation of the anal canal in the pig. A light- and electron-microscopical study.

The sensory innervation of the anal canal of the pig was investigated by light and electron microscopy. The distribution of the different types of sensory nerve endings correlates with the histology of different zones: (1) After the rectal mucosa there was a zone lined with nonkeratinized stratified squamous epithelium. (2) A middle zone was lined with keratinized stratified squamous epithelium. Here the dermis already showed a papillary and reticular layer. (3) The last zone showed hairy skin with a high hair density. The following nerve endings were found: Free nerve endings reached the stratum superficiale in nonkeratinized squamous epithelium and the stratum granulosum in the keratinized squamous epithelium. Dermal free nerve endings were found in all zones near the epithelium and two different types were identified as those derived from C-fibers and those from A-delta-fibers. Merkel nerve endings showed different features depending on their location. Few Merkel-like cells were found in the epithelium of the anal crypts. Typical Merkel Tastscheiben were located at the base of epithelial ridges or pegs in zones 2 and 3. The number of Merkel cells varied up to 200. The myelinated afferent fiber supplied 10-15 Merkel cells. Merkel cells were also found regularly in the outermost layer of the external rooth sheath of hair follicles at about the same level as perifollicular nerve endings. Lamellated corpuscles were found in the dermis of all zones except the cranial part of zone 1, where the anal crypts are located. Generally they consisted of a central nerve terminal which may be branched. Each terminal was surrounded by an inner core of concentrically arranged lamellae of the terminal Schwann cell and one or several inner cores were included in a capsule of perineural cells. The size of the corpuscle, the regularity of the inner core and the number of capsular layers depended on the location of the corpuscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of left ventricular contractile performance from baseline stress-shortening data in humans: comparison with pharmacological afterload challenge.

The purpose of this study was to evaluate whether the baseline stress-shortening data reflect the contractile state adequately and give results comparable to the evaluation of the end-systolic stress-shortening relationships using pharmacological manipulation of afterload. Five groups were studied (total 152 patients): a control group of 30 healthy volunteers, 32 patients after surgical correction of infantile tetralogy of Fallot, 50 patients treated for childhood malignancies with doxorubicin, 17 patients with left ventricular hypertrophy due to systemic hypertension, and 23 patients with congestive cardiomyopathy. In all patients except those with congestive cardiomyopathy, afterload was altered pharmacologically to evaluate the individual stress-shortening relationship. In all patients the baseline stress-shortening data were evaluated, as well as their relative positions to two predefined normal ranges for the relationship between end-systolic stress and shortening. Additionally, a slope value was calculated from the baseline data of the five groups studied and compared with the data obtained by pharmacological afterload increment. Our data show that the comparison of individual baseline data of end-systolic wall stress and fractional shortening with predefined normal ranges for the relationship between end-systolic stress and shortening is inadequate. The appropriate normal range to compare with is the 95% confidence interval of baseline stress-shortening data in normal subjects. Also the calculation of a slope value from the baseline stress-shortening data of a group of patients seems to be inappropriate.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertrophic obstructive cardiomyopathy in neonatal beta-cell adenoma of the pancreas.

A case of beta-cell adenoma of the pancreas in a neonate with congestive heart failure due to severe hypertrophic cardiomyopathy is reported. In the course of the illness, he developed myocardial infarction, which was probably caused by the limited coronary reserve of the hypertrophied myocardium.

The ultrastructure of sensory nerve endings in the human knee joint capsule.

The ultrastructure of sensory nerve endings in the human knee joint capsule was studied. Three types of nerve endings were found: free nerve endings (FNE), Ruffini corpuscles and Pacini corpuscles. In the joint capsule, FNE are located below the synovial layer and within the fibrous layer near blood vessels. These nerve terminals derive from myelinated A delta-fibres or from unmyelinated C-fibres. Their structure is almost identical to FNE in human hairy and non-hairy skin. Ruffini corpuscles are present within the fibrous layer and the ligaments of the capsule in three variations: small Ruffini corpuscles without a capsule, small with a connective tissue capsule, and large Ruffini corpuscles with an incomplete perineural capsule. Their afferent axons are myelinated and measure 3-5 micron in diameter. Inside the corpuscle, nerve terminals are anchored in the connective tissue belonging to the fibrous layer or to the ligaments respectively. The presence of an incomplete perineural capsule depends on the structure of the surrounding connective tissue. In ligaments with collagenous fibrils oriented in a parallel fashion, the perineural capsule is well-developed and the Ruffini corpuscle resembles a Golgi tendon organ; in areas where the fibrils show no predominant orientation, Ruffini corpuscles lack a capsule. Small Pacini corpuscles are situated within the fibrous layer near the capsular insertion at the meniscus articularis or at the periost. They consist of one or several inner cores and a perineural capsule of 1-2 layers. Larger Pacini corpuscles with one or several inner cores and a perineural capsule consisting of 20-30 layers are found on the outer surface of the fibrous layer. The ultrastructure of these nerve endings is compared with the ultrastructure of articular receptors of various animals and with the ultrastructure of sensory nerve endings in the skin of several mammalian species including man.

[Continuous frequency analysis (spectral trend analysis) in the evaluation of long-term EEG recordings]. / Die kontinuierliche Frequenzanalyse (spektrale Trendanalyse) in der Auswertung von EEG-Langzeitableitungen.

This study demonstrates the possibilities of continuous frequency analysis supporting the evaluation of long lasting EEG recordings which present problems in analysing large amount of data. Avoiding some disadvantages of the usual presentation of power spectra by compressed spectral array compression of the spectral data will be obtained in a more suitable way by sequential plots of the data on the abscissa as time axis. The spectra will be separated in only a few number of frequency bands. A special conversion procedure (linear multiplication of the data within each frequency band by logarithmic calculated factors) provides for the essential enhancement of low spectral power in the upper EEG frequency domain preserving the full dynamic of spectral variations. The efficiency of this spectral trend analysis is shown by two examples: (1) In the study of the variations of cerebral excitability in a patient with epileptic seizures depending on the waking-sleeping-cycle (Fig. 3), and (2) in the documentation of the EEG dynamics in the course of intensive care monitoring. Fig. 5 shows the development of a cerebral autorhythmicity representing reintegration of cerebral function in a patient with severe head injury.