Neonatal pneumothorax: symptoms, signs and timing of onset in the post-surfactant era.

AIM: The primary objective was to describe the incidence, symptoms, clinical signs, and time of onset of neonatal pneumothorax in Örebro County during 2011-2017. Secondary objectives were to describe risk factors, diagnostic procedures, treatments, and mortality and to compare preterm with term/post-term neonates. MATERIALS AND METHODS: This retrospective population-based descriptive study included all neonates born in Örebro County during 2011-2017 and admitted to the neonatal intensive care unit at Örebro University Hospital at age <28 days with an x-ray verified diagnosis of "Pneumothorax originating in the perinatal period" in their medical record. RESULTS: Seventy-five neonates matched the inclusion criteria. The incidence of neonatal pneumothorax in Örebro County during the study period was 3.1 (95% CI: 2.5-3.8) per 1000 live births. All neonates were <48 h at debut of respiratory symptoms and the most common symptom was tachypnea. Twelve (16%) received invasive treatment. The mortality rate was 2 (3%), none due to pneumothorax. CONCLUSION: The incidence of 3.1 per 1000 live births was relatively high, but the frequency of invasive treatment and mortality was low, indicating a high proportion of mild pneumothoraces. The lack of patients aged >48 h indicates that most neonatal pneumothoraces now occur very early in life.

Home phototherapy for hyperbilirubinemia in term neonates-an unblinded multicentre randomized controlled trial.

The aim of this study was to assess whether home phototherapy was feasible and safe in a cohort of otherwise healthy term-born neonates who fulfilled the criteria for in-hospital phototherapy. This was a randomized controlled trial in which term newborns with a total serum bilirubin of 18-24 mg/dL (300-400 µmol) were randomized to either home phototherapy or conventional in-hospital phototherapy. The primary outcome measurements were safety and efficacy, length of stay and the number of failed treatments. The secondary outcomes were the number of blood samples and weight gain during treatment. One hundred forty-seven patients were recruited, 69 patients randomized to conventional phototherapy and 78 to home phototherapy. The results showed that no patients needed blood exchange and only 4% of the patients allocated to home phototherapy were admitted to the hospital. The duration of phototherapy, length of stay, amount of blood tests and weight change showed no statically significant differences.Conclusion: Home phototherapy could be a safe alternative to inpatient phototherapy for otherwise healthy newborns with hyperbilirubinemia if daily checkups and 24/7 telephone support can be provided. The parents should be informed to contact the hospital immediately if they fail to perform the treatment at home.Trial registration: Clinicaltrials.gov NCT03536078 What is Known: • Phototherapy in the hospital is a safe and effective treatment without major side effects. • Fibre optic equipment has made the choice of home phototherapy possible. What is New: • This is the first randomized controlled trial comparing home phototherapy with hospital phototherapy. • Results indicate that home phototherapy could be considered as a safe and feasible alternative when performed according to instructions given, to hospital treatment for otherwise healthy term newborns.

Outcome after hip arthroscopy for femoroacetabular impingement in 289 patients with minimum 2-year follow-up.

Femoroacetabular impingement (FAI) is a common cause of hip pain and dysfunction. The purpose of this study was to report outcome 2 years after the arthroscopic treatment of FAI using validated outcome measurements. Two hundred and eighty-nine patients (males = 190, females = 99) with a mean age of 37 years underwent arthroscopic surgery for FAI. Patients were included consecutively in a hip arthroscopy registry. The cohort was evaluated using online web-based validated health-related patient-reported outcomes measurements, including the iHOT-12, HAGOS, EQ-5D, HSAS for physical activity level, VAS for overall hip function and overall satisfaction. The mean follow-up time was 25.4 months. Pre-operative scores compared with those obtained at follow-up revealed statistically and clinically significant improvements (P < 0.05) for all measured outcomes; iHOT-12 (43 vs 66), VAS for global hip function (50 vs 71), HSAS (2.9 vs 3.6), EQ-5D index (0.58 vs 0.75), EQ-VAS (67 vs 75) and HAGOS different subscales (56 vs 76, 51 vs 69, 60 vs 78, 40 vs 65, 29 vs 57, 33 vs 58). At the 2-year follow-up, 236 patients (82%) reported they were satisfied with the outcome of surgery. We conclude that arthroscopic treatment for FAI resulted in statistically and clinically significant improvements in outcome parameters.

Serum level of cartilage oligomeric matrix protein is lower in children with idiopathic scoliosis than in non-scoliotic controls.

PURPOSE: The etiology of idiopathic scoliosis remains unknown, but growth is a risk factor for progression. Growth pattern differs in children with and without scoliosis. Cartilage oligomeric matrix protein (COMP) may be associated with scoliosis and growth. We, therefore, studied COMP in children with and without idiopathic scoliosis. METHODS: We included 105 children, with mean age 14.4 years (range 10-16), under observation or treatment for idiopathic scoliosis, and 103 children from an age-matched population-based cohort. COMP was measured in serum at the time of inclusion. Growth velocity was estimated from repeated height measurements. T tests, analysis of covariance or linear regression were used for statistical comparisons. RESULTS: COMP was mean (SD) 11 (5) units/liter (U/L) in children with scoliosis and 13 (5) U/L in the control cohort (p = 0.005, adjusted for sex and sampling time of the day). When patients and controls were analyzed together, high COMP was correlated with high growth velocity (ß = 0.19, p = 0.003). When patients and controls were analyzed separately, COMP was correlated with growth velocity in children with scoliosis (ß = 0.27, p = 0.007), but not in children without scoliosis (ß = 0.02, p = 0.83) (all analyses adjusted for age, sex and sampling time). Low COMP was significantly correlated with large curve size in children with scoliosis (ß = -0.29, p = 0.003), but not after adjustment for age, sex and sampling time (ß = -0.16; p = 0.14). CONCLUSION: COMP was lower in children with idiopathic scoliosis than in a control cohort. In children with scoliosis, high COMP was modestly correlated with high growth velocity, but not with curve severity.

Evaluation of a commercial multiplex PCR test (SeptiFast) in the etiological diagnosis of community-onset bloodstream infections.

The commercial polymerase chain reaction (PCR) test, SeptiFast, is designed to identify the DNA of individual bacterial and fungal pathogens in whole blood. We aimed to evaluate the usefulness of the test for the detection of community-onset bloodstream infections. We prospectively included adult patients who were subjected to blood culture (BC) at an infectious diseases department. For the evaluation, one BC/PCR set (two BC bottles and one PCR tube) per patient was used. When several sets were obtained and analyzed, the first set with any positive result was evaluated. Among 1,093 consecutively included patients, BC was positive in 138 and PCR was positive in 107. Fifty positive PCR results were supported by BC in the same BC/PCR set, ten were supported by other cultures, and, additionally, ten were supported by the clinical presentation. Compared with BC, PCR showed specificities and negative predictive values of >97% for all detectable pathogens. The following sensitivities and positive predictive values (PPVs) were noted: Staphylococcus aureus, 67% and 43%; Streptococcus pneumoniae, 12% and 67%; other Streptococcus species, 43% and 77%; Escherichia coli, 53% and 56%; and Klebsiella species, 43% and 23%. If support from other cultures and the clinical presentation were included in the reference standard, the PPVs for the detection of these bacteria were 57%, 100%, 92%, 75%, and 69%, respectively. Although the specificities were high, the low sensitivities and suboptimal PPVs noted in the present study discourage routine use of the test in its present form for the detection of community-onset bloodstream infections.

Rapid typing of neonatal Staphylococcus epidermidis isolates using polymerase chain reaction for repeat regions in surface protein genes.

Staphylococcus epidermidis is a significant pathogen in neonatal sepsis and other nosocomial infections. For further investigations of the colonisation patterns and invasive pathways, typing methods that are applicable on large populations of bacterial isolates are warranted. In the present study, a genotyping method based on polymerase chain reaction (PCR) for the repeat regions of four genes (sdrG, sdrF, aap and sesE) that encode for bacterial surface proteins was developed and applied to a sample of well-characterised neonatal blood isolates of S. epidermidis (n = 49). The PCR products were visualised on agarose gel (sdrG, sdrF and sesE) or by fragment analysis (aap). The discriminatory index (D-index) for genotyping of the different genes was compared to genotyping by pulsed-field gel electrophoresis (PFGE). The highest D-index for the PCR-based typing methods was found for the combination of sdrF, sdrG and aap (D-index 0.94), whereas the optimal two-gene combination (sdrF and aap) resulted in a D-index of 0.92. We conclude that the described method can be used for the genotyping of large populations of S. epidermidis isolates with a sufficient discriminatory capacity, and we suggest that the combination of sdrF and aap is the most suitable to use.

Radiation Dose Optimization in CT Planning of Corrective Scoliosis Surgery. A Phantom Study.

The aim of the study was to explore the possibility of obtaining a helical CT scan of a long segment of vertebral column, optimally reduce the radiation dose, compare the radiation dose of the low dose helical CT with that of some of the CT protocols used in clinical practice and finally assess the impact of such a dose reduction on the image quality. A chest phantom was examined with a 16-slice CT scanner. Six scans were performed with different radiation doses. The lowest radiation dose which had no impact on image quality with regard to the information required for surgical planning of patients with scoliosis, was 20 times lower than that of routinely used protocol for CT examination of the spine in children (0.38 mSv vs 7.76 mSv). Patients with scoliosis planned for corrective spinal surgery can be examined with low dose helical CT scan. The dose reduction systems (DRS) available in modern CT scanners contribute to dose reduction and should be used.

Soluble thrombomodulin activity and soluble thrombomodulin antigen in plasma.

Endothelial cell membrane-bound thrombomodulin (TM) plays a critical role as a cofactor in the protein C pathway, important in regulating coagulation as well as inflammation. Heterogeneous soluble TM fragments circulate in the plasma and are found at increased levels in various diseases such as cardiovascular disease and diabetes, and in ischemic and/or inflammatory endothelial injuries. The anticoagulant function of these soluble fragments has not been measured in healthy individuals or in patients. Using an immobilized monoclonal antibody against TM and a microtiter plate format, an assay was designed to capture the soluble TM fragments in plasma and measure their cofactor activity in the thrombin-mediated activation of protein C. In addition, soluble TM antigen levels were measured by enzyme-linked immunosorbent assay. Both assays were used to investigate a group of healthy blood donors. TM fragments released into plasma were shown to retain significant cofactor activity, and reference intervals for healthy men and women were established. Furthermore, a statistically significant correlation was observed between soluble TM antigen levels and soluble TM cofactor activity. This notwithstanding, soluble TM activity only accounted for a minor part of all variation in soluble TM antigen levels (R2 = 22% in men and R2 = 16% in women).

Screening for pulmonary hypertension in systemic sclerosis: the longitudinal development of tricuspid gradient in 227 consecutive patients, 1992-2001.

OBJECTIVE: To evaluate the longitudinal development of the tricuspid gradient (TG) for screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc). METHODS: Doppler echocardiography was performed 506 times in order to estimate TG in 227 consecutive patients with SSc. The value of biochemical markers for predicting TG levels and development was assessed through analyses of pro-brain natriuretic peptide (proBNP), calcitonin-gene related peptide, thrombomodulin and von Willebrand factor in 76 patients with a borderline increase in TG, defined as TG 24-38 mmHg, and for the purpose of comparison also in 10 patients with a normal TG (< 23 mmHg) and in 10 patients with increased TG (TG > 38 mmHg). RESULTS: TG > 23 mmHg was found in 102 patients (44.9%) at the first assessment point and in 139 patients (61.2%) respectively, cumulatively at follow-up. TG values > 33 mmHg were measured in 24 patients (10.6%) initially and in 38 patients (16.7%) cumulatively in a subsequent assessment. Age and the presence of interstitial lung disease (ILD) were associated with more frequent occurrence of TG > 23 and > 33 mmHg initially and at follow-up, but were not associated with progression rate. The change in TG (mean +/- S.D.) was 1.34 +/- 4.55 mmHg/yr. ProBNP correlated to TG. CONCLUSION: An increased TG, indicating possible PAH, is common and progressive in SSc. Age and ILD increase the risk of increased TG. Patients with or without ILD have similar progression of TG. ProBNP has potential as an adjunct to TG in selecting patients eligible for invasive treatment.

Spatial facilitation of motor evoked responses in monitoring during spinal surgery.

During spinal cord monitoring, motor responses in the tibialis anterior muscles were recorded on transcranial electrical stimulation of the motor cortex. In order to facilitate the responses, the cortical stimulus was preceded by a train of stimuli to the foot sole within the receptive field of the withdrawal reflex of the tibialis anterior muscle. This cutaneous input provides a spatial facilitation of the cortically elicited response. When the stimulus interval was 50-100 ms, large and reliable responses were seen in most cases.

Bone resorbing activity released from zymosan-activated mouse peritoneal macrophages--the role of prostanoids and interleukin-1.

OBJECTIVE: To study the effect of zymosan on the release of osteoclast stimulating activity from macrophages. MATERIALS: Calvarial bones from neonatal mice and peritoneal macrophages were incubated in the absence and presence of zymosan for 72 h and supernatants harvested for subsequent analysis of bone resorbing activities and prostaglandin concentration. METHODS: Bone resorption was assessed in vitro by analysing the release of 45Ca and 3H from neonatal mouse calvarial bones prelabelled in vivo by injections of [45Ca]CaCl2 or [3H]-proline. Prostaglandin E2 (PGE2) and I2 (PGI2) were analyzed using radioimmunoassays. RESULTS: Supernatants from macrophages treated with zymosan stimulated the release of 45Ca and 3H. The amount of bone resorbing activity present in the macrophage supernatants was dependent on the concentration of zymosan (0.1-100 microg/ml), as well as the number of macrophages present. The 45Ca release induced by zymosan treated macrophages was inhibited by three different inhibitors of osteoclastic bone resorption (calcitonin, acetazolamide, amino bisphosphonate). The bone resorbing activity released by the zymosan-activated macrophages was lost after ultrafiltration using a filter with a molecular weight cut off of 30,000 Daltons, but retained when using a filter with a cut off of 3000 Daltons. Time-course studies of the production of bone resorbing activity in macrophages showed that activity increased during the first hour of exposure to zymosan and then reached a plateau for 96 h. PGE2 and PGI2 release from macrophages was increased during the first three hours of exposure to zymosan. This prostanoid production, together with bone resorbing activity, was abolished by indomethacin. The bone resorbing activity present 3-72 h after zymosan exposure, however, was not inhibited by indomethacin. Bone resorption stimulated by conditioned media from zymosan treated macrophages after 3 h was inhibited by 60-75% in the presence of anti IL-1alpha, 0-20% by anti IL-1beta, and completely by antisera neutralizing both IL-1alpha and IL-1beta. In addition, an IL-1 receptor antagonist abolished the stimulatory effect of conditioned media from zymosan treated macrophages. CONCLUSIONS: These data indicate that treatment of mouse peritoneal macrophages with zymosan results in production of activities capable of stimulating bone resorption in vitro. The activity released initially appears to be due to a zymosan induced burst of prostanoid production, while the activity released during prolonged exposure to zymosan is due primarily to IL-1alpha.

Thrombomodulin gene defects in families with thromboembolic disease--a report on four families.

It has been suggested that an impaired thrombomodulin (TM) function could constitute an abnormality leading to thromboembolic disease (TED). The TM gene from 51 unrelated American patients with TED and 100 American blood donors was screened for mutations. Four heterozygous point mutations in the TM gene were detected. The mutations are distributed throughout the TM gene and predict amino acid changes 1) Pro483 to Leu, 2) Gly61 to Ala, 3) Asp468 to Tyr (earlier described) and 4) a silent mutation not predicting any amino acid change at Glu163. Family studies reveal that the occurrence of the different TM mutations is associated with a history of TED, but there are indications of multiple risk factors and no perfect co-segregation of the TM defects and TED. Among the controls. three individuals carried heterozygous TM variants predicting either a Pro477-Ser mutation (two cases) or an Asp468-Tyr mutation. Our results thus demonstrate that a previously undocumented abnormality in the protein C anticoagulant pathway, a defect in the TM gene, to a certain extent co-segregates with familial thrombophilia. Further studies are needed to prove the causality of these TM mutations.

Gutta-percha-stimulated mouse macrophages release factors that activate the bone resorptive system of mouse calvarial bone.

This study investigated the capacity of macrophages exposed to gutta-percha particles to produce factors affecting bone metabolism. Peritoneal mouse macrophages were isolated and incubated with and without gutta-percha particles, and the supernatants were assessed for bone resorbing activity by adding macrophage-conditioned media to cultures of neonatal mouse calvarial bones. Bone resorption was measured by mineral mobilization (45Ca release) and matrix degradation (3H from [3H]proline labelled bones). The results showed that supernatant from gutta-percha-stimulated macrophages enhanced bone resorption. This effect was related to the amount of gutta-percha, and the concentration and time of exposure to the conditioned media. Stimulated macrophages released enhanced amounts of prostaglandins E2 and I2; however, indomethacin, which inhibits the prostanoid response, had no effect on bone resorbing activity. The stimulatory effect on bone resorption was inhibited by calcitonin, interleukin-1 receptor antagonistic protein, and by antiserum neutralizing mouse interleukin-1alpha(IL-1alpha), but not by anti-IL-1beta. Filtration experiments revealed that the molecules involved in the resorption activity had an apparent molecular weight between 3000 and 30,000 Da. These experiments show that mouse peritoneal macrophages, when exposed to gutta-percha particles, release factors which have a bone resorbing activity that is primarily due to enhanced production of IL-1alpha.

Bacteria inhibit biosynthesis of bone matrix proteins in human osteoblasts.

The effect of extracts from Staphylococcus aureus and Staphylococcus epidermidis on bone matrix production were assessed by analyzing the biosynthesis of osteocalcin and Type I collagen in a human osteoblastic osteosarcoma cell line (MG-63). In MG-63 cells, extracts from Staphylococcus aureus and Staphylococcus epidermidis decreased 1,25(OH)2-vitamin D3 stimulated osteocalcin biosynthesis, and insulin-like growth factor I induced production of Type I collagen in a concentration dependent manner. The basal rate of osteocalcin and Type I collagen formation was unaffected by the bacterial extracts. The inhibitory effect of the bacteria on osteocalcin biosynthesis was seen after 24 hours of treatment and was maintained for at least 96 hours. The extracts of Staphylococcus aureus and Staphylococcus epidermidis enhanced prostaglandin E2 formation in the MG-63 cells. Abolition of the prostaglandin E2 response by treatment with indomethacin and flurbiprofen did not affect bacteria induced inhibition of osteocalcin production. Stimulation of osteocalcin biosynthesis by 1,25(OH)2-vitamin D3 was associated with a decreased rate of cell proliferation. The inhibitory action of the bacterial extracts was not linked to any inhibition of [3H]-thymidine incorporation into deoxyribonucleic acid. These data show that extracts of Staphylococcus aureus and Staphylococcus epidermidis have the ability to inhibit the biosynthesis of bone matrix proteins by a nonprostaglandin and noncytotoxic dependent mechanism and suggest that bone loss in inflammatory processes containing Staphylococcus aureus or Staphylococcus epidermidis may not be caused only by enhanced bone resorption but also by decreased bone formation.

A 50-year perspective of a family with chromosome-14-linked Alzheimer's disease.

A Swedish family with two generations suffering from presenile dementia with an unusually severe Alzheimer encephalopathy was first reported in 1946. The hypothesis that the disease was inherited through a dominant gene is strongly supported by the follow-up 50 years later of three additional generations and molecular genetic findings of a novel presenilin-1 gene mutation in the family. The pedigree contains six cases with well-documented dementia in four consecutive generations. The Alzheimer encephalopathy was unusually severe in the three cases studied post-mortem, with a pronounced involvement of the central grey structures, such as the claustrum, the nuclei around the third ventricle, the central thalamic nuclei and the brain stem. There were no vascular lesions and little amyloid angiopathy. All six affected cases showed the typical temporoparietal symptom pattern and other core symptoms of Alzheimer's disease, such as logoclonia, myoclonic twitchings and major motor seizures. Other predominant features were psychomotor slowness, increased muscular tension, a stiff stooped gait and a rapid loss of weight. The symptom pattern is convincingly explained by the consistent and severe involvement of cortical and central grey structures and is probably linked to the presenilin-1 gene mutation.

Association of vitamin K-dependent coagulation proteins and C4b binding protein with triglyceride-rich lipoproteins of human plasma.

The triglyceride (TG) concentration in plasma is an independent risk factor for coronary heart disease. There is evidence that TG-rich lipoprotein (TGRLP), ie, chylomicrons (CMs), chylomicron remnants (CMRs), and VLDLs associate with factor VII and prothrombin and that the association enhances a platelet factor Xa-mediated prothrombin activation when the CM-prothrombin complex is exposed to platelets. In this study, we examined the association of the vitamin K-dependent coagulation factors VII, IX, X, and prothrombin, as well as the anticoagulation protein C and its cofactor protein S, in plasma lipoproteins obtained from human fasting and postprandial plasma. We also analyzed some other proteins that are related to the coagulation system but not to vitamin K-dependent proteins, including factor V, serum amyloid P component (SAP), C4b binding protein (C4BP), and thrombomodulin (TM), and as a control, Ig G. Human TGRLP (d < 1.006 kg/L), LDL (d = 1.006 to 1.063 kg/L), and HDL (d = 1.063 to 1.210 kg/L) were separated from normal subjects both in fasting and 2 to 3 hours after the ingestion of a meal containing 100 g fat. The different coagulation proteins, SAP, C4BP, TM, and Ig G were determined by SDS-polyacrylamide gel electrophoresis combined with Western blotting, using specific polyclonal or monoclonal antibodies, and were visualized by peroxidase staining. All the vitamin K-dependent proteins associate with TGRLP in both fasting and postprandial plasma, but not with LDL or HDL. Factor V, SAP, TM, and Ig G were not found in any lipoprotein classes. C4BP, which is a regulatory protein of the classic pathway of the complement system and which binds protein S in vivo to regulate blood coagulation, was present in TGRLP, especially postprandial, but not in LDL or HDL. The amounts of prothrombin, protein S, and C4BP in postprandial TGRLP were larger than those in fasting TGRLP. Vitamin K-dependent procoagulation and anticoagulation proteins, as well as C4BP, could be associated with TGRLP in vivo. If the association enhances prothrombin activation, this effect may thus be counteracted by simultaneous binding of protein S.

Effect of intravenous nitroglycerin on lipid peroxidation after thrombolytic therapy for acute myocardial infarction.

Free oxygen radicals are produced after coronary artery occlusion and reperfusion. Polyunsaturated fatty acids are oxidized by free radicals to lipid peroxides. Measurements of plasma malondialdehyde (MDA) formed by the breakdown of lipid peroxides are often used as markers of lipid peroxidation. The effect of intravenous nitroglycerin on plasma MDA levels was studied in 43 patients who received thrombolytic therapy for acute myocardial infarction. Plasma MDA levels in patients were elevated on admission to the hospital compared with healthy controls, and normalized within 48 hours. A greater increase in plasma MDA concentrations after thrombolysis was found in patients with noninvasive signs of reperfusion than in patients judged to have a persistent occlusion. In the 23 patients receiving immediate intravenous nitroglycerin infusion, plasma MDA levels did not change from baseline to 90 minutes (0.92+/-0.22 and 0.92+/-0.23 micromol/L, p=0.99), whereas a significant increase was found in the 20 control patients who did not receive nitroglycerin (from 0.83+/-0.22 to 1.01+/-0.30 micromol/L, p=0.0004) (p=0.036 for the difference between groups). Successful reperfusion after thrombolytic therapy entails increased lipid peroxidation. Intravenous nitroglycerin reduces lipid peroxidation during myocardial ischemia and reperfusion.

A novel thrombomodulin gene mutation in a patient suffering from sagittal sinus thrombosis.

Thrombomodulin is an endothelial cell membrane glycoprotein that promotes protein C activation. It has been clearly demonstrated that the anticoagulant functions of the protein C system are important in the prevention of thromboembolic disease. Patients with protein C or protein S deficiency and/or resistance to activated protein C (APC resistance) are at higher risk for developing thromboembolic disease. The first mutation in the thrombomodulin gene was discovered in an American patient suffering from pulmonary embolism at the age of 45 (Ohlin and Marlar 1995). Here we report a case of sagittal sinus thrombosis in a 42-year-old Swedish woman. She was found to carry a heterozygous point mutation changing G127 to A, predicting an Ala25 to a Thr change in the mature thrombomodulin protein. This mutation was also found in her 16-year-old daughter, who so far has not suffered from any thrombotic events. The patient had no other detectable prothrombotic genetic defects associated with the coagulation system. This case supports the hypothesis of an association between mutations in the thrombomodulin gene and venous thrombosis.