Reference Values for Placental Weight and Placental:Fetal Weight Ratio in a Swedish Population.

INTRODUCTION: There is important clinical information from placental weight and its ratio to the fetal weight. The aim with this study was to establish reference values for the placental weight and the placental:fetal weight ratio for gestational weeks 13-43 in a Swedish population. MATERIALS AND METHODS: Cases were retrospectively collected from the database used at the Pathology Department at Karolinska University Hospital and information about the placental weight, fetal weight, and gestational age was retrieved. Conditions, which could affect the placental- or fetal weight were excluded. Thereafter percentile curves were calculated for the placental weight and the placental:fetal weight ratio for gestational weeks. RESULTS: A total of 730 cases were included and percentile curves for the placental weight for gestational week 13-43 and placental:fetal weight ratio for gestational week 18-43 are presented. CONCLUSIONS: Reference values for post fixation placental weight and its ratio to fetal weight for a Swedish population are presented. The reference values are lower than the current reference values used in our institution, and this will be of importance when interpreting findings after placental examination.

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission.

OBJECTIVE: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress. DESIGN: Retrospective, observational. SETTING: Nationwide. POPULATION: Five stillborn and nine live-born infants from 13 pregnant women infected with SARS-CoV-2 seeking care at seven different maternity units in Sweden. METHODS: Clinical outcomes and placental pathology were studied in 14 cases (one twin pregnancy) of maternal SARS-CoV-2 infection with impaired fetal outcome. Outcomes were correlated to placental pathology in order to investigate the impact of virus-related pathology on the villous capillary endothelium, trophoblast and other cells. MAIN OUTCOME MEASURES: Maternal and fetal clinical outcomes and placental pathology in stillborn and live-born infants. RESULTS: Reduced fetal movements were reported (77%) and time from onset of maternal COVID-19 symptoms to signs of fetal distress among live-born infants was 6 (3-12) days and to diagnosis of stillbirth 11 (2-25) days. Two of the live-born infants died during the postnatal period. Signs of fetal distress led to emergency caesarean section in all live-born infants with umbilical cord blood gases and low Apgar scores confirming intrauterine hypoxia. Five stillborn and one live-born neonate had confirmed congenital transmission. Massive perivillous fibrinoid deposition, intervillositis and trophoblast necrosis were associated with SARS-CoV-2 placental infection and congenital transmission. CONCLUSIONS: SARS-CoV-2 can cause rapid placental dysfunction with subsequent acute fetal hypoxia leading to intrauterine fetal compromise. Associated placental pathology included massive perivillous fibrinoid deposition, intervillositis and trophoblast degeneration.

Is obesity in pregnancy associated with signs of chronic fetal hypoxia?

INTRODUCTION: The prevalence of obesity in pregnancy is increasing worldwide. Maternal obesity increases risks of severe fetal and neonatal complications. The underlying pathophysiological mechanisms are unclear. One possible contributing factor could be chronic fetal hypoxia. The aim of this study was to compare placentas from women with and without obesity with respect to placental lesions, which could reflect compensatory mechanisms in response to chronic fetal hypoxia as well as lesions possibly leading to chronic fetal hypoxia. In addition, levels of erythropoietin in cord blood were compared between offspring of lean and obese women. MATERIAL AND METHODS: This cohort study included 180 women with uneventful, full-term, singleton pregnancies, out of which 91 lean women had a body mass index (BMI) of 18.5-24.9 kg/m2 and 89 women had obesity (BMI ≥30 kg/m2 ). Women were recruited at Södersjukhuset between 16 October 2018 and 2 December 2019. Placentas were investigated by two senior perinatal pathologists, who were blinded for maternal BMI. Cord blood was analyzed for levels of erythropoietin. RESULTS: Levels of erythropoietin in cord blood increased with maternal BMI (P = .01, ß = 0.97, 95% CI 0.27-1.68). There was no difference between placentas of obese and lean women in number of placental lesions reflecting chronic fetal hypoxia or in lesions that could possibly lead to chronic fetal hypoxia. CONCLUSIONS: This study of term and uneventful pregnancies demonstrated a positive association between maternal obesity and concentrations of erythropoietin in cord blood at birth. This finding supports the hypothesis of chronic fetal hypoxia as a risk factor for complications in the pregnancies of obese women. There were no differences in lesions associated with hypoxia between placentas of obese and lean women.

Genetic Analysis of Copy Number Variation in Large Chorangiomas.

INTRODUCTION: Chorangioma (CA) is the most common nontrophoblastic, vascular tumor-like lesion of the placenta with a reported incidence of 0.5% to 1% in all examined placentas. The underlying molecular mechanisms of CAs are still poorly elucidated, and a systematic investigation of the genetic background of CAs has not previously been done. MATERIALS AND METHODS: Tissue biopsies from 8 large (>40 mm) histologically confirmed CAs and 8 unaffected matched placenta controls, along with standard control DNA samples were analyzed for large genomic deletions and duplications using array comparative genomic hybridization (array-CGH) method. RESULTS: Array-CGH analysis revealed no rare or novel copy number variants in the CA samples compared with either standard control DNA or unaffected placenta DNA from the same individual. DISCUSSION: In this study, a systematic genetic investigation of 8 large CAs failed to demonstrate any large-scale pathogenic genetic changes. This lack of association might support a nongenetic, nontumorous origin of these lesions; however, additional genetic studies focusing on smaller genomic alterations are required to fully assess any possible genetic contribution.

Placental inflammation, lifestyle, maternal and early child sensitisation to allergens - the assessment of lifestyle and allergic disease during infancy birth cohort.

AIM: To investigate (i) whether maternal sensitisation to allergens, and lifestyle can influence the risk of acute and chronic inflammation of the placenta, in the forms of chorioamnionitis and villitis, respectively, and (ii) whether these placental inflammations are associated with the outcome of sensitisation for the child during preschool age. METHODS: Placentas from term uncomplicated pregnancies (n = 275) in the assessment of lifestyle and allergic disease during infancy study were analysed for the presence of acute chorioamnionitis and chronic villitis. Stepwise logistic regression was performed to estimate the relative risk of placental inflammation in relation to maternal allergic sensitisation and lifestyle, and the association between placental inflammation and sensitisation of the child up to five years of age. RESULTS: Parity and delivery at home were independently associated with chorioamnionitis, home delivery only with the low grade. Maternal allergic sensitisation was associated with increased risk of villitis in the bivariable model, however, not in the multivariable model. No significant associations were detected between placental inflammation and the outcome of sensitisation to allergens at five years of age. CONCLUSION: Our data do not support the hypothesis that the increased risk for sensitisation of a child when the mother is allergic is mediated via placental inflammation.

Targeted copy number screening highlights an intragenic deletion of WDR63 as the likely cause of human occipital encephalocele and abnormal CNS development in zebrafish.

Congenital malformations affecting the neural tube can present as isolated malformations or occur in association with other developmental abnormalities and syndromes. Using high-resolution copy number screening in 66 fetuses with neural tube defects, we identified six fetuses with likely pathogenic mutations, three aneuploidies (one trisomy 13 and two trisomy 18) and three deletions previously reported in NTDs (one 22q11.2 deletion and two 1p36 deletions) corresponding to 9% of the cohort. In addition, we identified five rare deletions and two duplications of uncertain significance including a rare intragenic heterozygous in-frame WDR63 deletion in a fetus with occipital encephalocele. Whole genome sequencing verified the deletion and excluded known pathogenic variants. The deletion spans exons 14-17 resulting in the expression of a protein missing the third and fourth WD-repeat domains. These findings were supported by CRISPR/Cas9-mediated somatic deletions in zebrafish. Injection of two different sgRNA-pairs targeting relevant intronic regions resulted in a deletion mimicking the human deletion and a concomitant increase of abnormal embryos with body and brain malformations (41%, n = 161 and 62%, n = 224, respectively), including a sac-like brain protrusion (7% and 9%, P < 0.01). Similar results were seen with overexpression of RNA encoding the deleted variant in zebrafish (total abnormal; 46%, n = 255, P < 0.001) compared with the overexpression of an equivalent amount of wild-type RNA (total abnormal; 3%, n = 177). We predict the in-frame WDR63 deletion to result in a dominant negative or gain-of-function form of WDR63. These are the first findings supporting a role for WDR63 in encephalocele formation.

Testing strategies to reduce morbidity and mortality from Lynch syndrome.

OBJECTIVE: Lynch syndrome (LS) has an autosomal dominant inheritance pattern and is associated with increased risk for colorectal cancer (CRC) and other cancers. Various strategies are used to identify patients at risk and offer surveillance and preventive programs, the cost effectiveness of which is much dependent on the prevalence of LS in a population. Universal testing (UT) is proposed as an effective measure, targeting all newly diagnosed CRC patients under a certain age. MATERIALS AND METHODS: LS cases were identified in a cohort of 572 consecutive CRC patients. Immunohistochemistry was performed in 539 cases, using antibodies against mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. Microsatellite instability and gene mutation screening were performed in 57 cases. RESULTS: In total 11 pathogenic variants were detected, identifying LS in 1.9% of new CRC cases. Comparing the results with current clinical methods, 2 pathogenic variants were found with Amsterdam criteria and 9 when using either Bethesda guidelines or our institution's prior clinical criteria. Pathogenic variants in MSH6 were the most common in our series. We also found different outcomes using different age cut offs. CONCLUSION: Our study demonstrates that UT of tumors before age on onset at 75 years would most likely be cost-efficient and essentially equivalent to applying the Bethesda guidelines or our institution's prior clinical criteria on all new CRC.

Temporal trends in incidence and outcome of hydatidiform mole: a retrospective cohort study.

BACKGROUND: Reported incidence rates of hydatidiform mole (HM) show wide geographic and temporal variations, making reliable international comparisons difficult. The aim of the current study was to examine temporal trends in the incidence of HM and post-molar gestational trophoblastic neoplasia (GTN) in Stockholm County. MATERIAL AND METHODS: Data of all women with a diagnosis of HM in Stockholm County 1991-2010 was collected. The incidence of HM was assessed both in relation to number of births and viable conceptions (births and pregnancy terminations). The risk of post-molar GTN was analysed for all HM, as well as for the subtypes complete (CHM) and partial hydatidiform mole (PHM). Temporal trends were analysed by stratifying the study period into five-year intervals. RESULTS: The overall incidence rate of HM was 2.08/1000 deliveries and 1.48/1000 viable conceptions. A significant temporal increase in the incidence rate of HM, as well as in the total number and proportion of PHM, was seen. Among 956 women with HM, 77 (8%) progressed into post-molar GTN. There was evidence of a slight, but non-significant increase in the risk of malignancy in the two last five-year periods under study. CONCLUSIONS: We found evidence of a significant temporal increase in the incidence rate of HM, which could not fully be explained by an increase in maternal age over time. Changes in diagnostic methods probably contributed to the increased incidence rate of PHM. The risk of post-molar GTN remained constant over time.

Antenatal corticosteroid treatment and placental pathology, with a focus on villous maturation.

INTRODUCTION: Mothers at risk of preterm birth are treated with antenatal corticosteroids, which have advantageous effects for prematurely born infants. Accelerated villous maturation in the placenta is also associated with improved perinatal outcome. The primary aim of this study was to examine the association between antenatal corticosteroids and accelerated villous maturation. The secondary aim was to study associations with other placental pathologies. MATERIAL AND METHODS: A retrospective cohort study including 105 women who had (n = 75) or had not (n = 30) been treated with antenatal corticosteroids. The women gave birth between 22+0 and 26+6  weeks of gestation in Stockholm County between 1 April 2004 and 31 March 2007. A pathologist blinded to all clinical data except gestational age examined the placental slides to identify pathology parameters. The outcomes were correlated with antenatal corticosteroid treatment, and confounding factors were adjusted using logistic regression. RESULTS: Accelerated villous maturation was significantly higher in the group treated with corticosteroids (odds ratio 16, 95% CI 2.4-690, p = 0.0005). After adjustment for gestational age and preeclampsia, the difference remained significant (odds ratio 8.9, 95% CI 1.2-389, p = 0.021). No significant associations were found regarding the secondary outcome variables, after adjusting for possible confounders. CONCLUSIONS: Antenatal corticosteroid treatment before preterm birth is associated with accelerated villous maturation. This could be one of the pathways by which corticosteroids are beneficial for preterm infants.

More histologic and ultrastructural degenerative signs in the subscapularis tendon and the joint capsule in male patients with shoulder impingement.

PURPOSE: The purpose of the present study was to analyze biopsy samples from the subscapularis tendon and from the joint capsule from male patients with shoulder impingement syndrome (SAIS) and compare them with samples from male patients with post-traumatic recurrent shoulder instability. The hypothesis of the study was that patients with SAIS would have more histologic and ultrastructural degenerative changes in their subscapularis tendon and joint capsule than patients with post-traumatic recurrent shoulder instability. METHODS: Male patients scheduled for surgery, with either subacromial decompression or Bankart reconstruction, were included. Four biopsies from each patient were obtained from the capsule and four from the subscapularis tendon during arthroscopic surgery. The histologic characteristics and the presence of glycosaminoglycans were assessed using the light microscope, and the ultrastructure was assessed using a transmission electron microscope. RESULTS: Eight patients, median age 53 (45-74) years (p < 0.0001), were included in the impingement group, and 12 patients, median age 27 (22-48) years, were included in the instability group. The histologic assessment revealed significantly higher cellularity and total degeneration score in the capsule (p = 0.016 and p = 0.014 respectively) in patients with subacromial impingement compared with the instability patients. The corresponding finding was not made for the subscapularis tendon. The ultrastructural evaluation revealed that the instability patients had more fibrils with a large diameter (indicating less degeneration) in both the subscapularis tendon and the capsule compared with the impingement patients (p < 0.0001). CONCLUSION: Male patients with subacromial impingement have more histologic and ultrastructural degenerative changes in their shoulder compared with patients with post-traumatic recurrent shoulder instability. CLINICAL RELEVANCE: It appears that in patients with subacromial impingement, the whole shoulder joint is affected and not only the subacromial space. It is the opinion of the authors that intra-articular therapeutic injections could be tried more often in these patients. LEVEL OF EVIDENCE: III.

Placental pathology in relation to stillbirth and neonatal outcome in an extremely preterm population: a prospective cohort study.

OBJECTIVE: To study associations between placental histopathology and stillbirth as well as neonatal outcome in a population born extremely preterm. DESIGN: Prospective cohort study. SETTING: Stockholm, Sweden. POPULATION: 167 infants born <27 gestational weeks during 2004-2007. METHODS: One senior perinatal pathologist, blinded to outcome data, evaluated all placental slides. MAIN OUTCOME MEASURES: Intrauterine fetal death, small-for-gestational age, major neonatal morbidity (intraventricular hemorrhage ≥grade 3, retinopathy of prematurity ≥grade 3, necrotizing enterocolitis, cystic periventricular leukomalacia or severe bronchopulmonary dysplasia) and neonatal mortality. Additional outcome variables were Apgar score at 5 min, sepsis, and treated patent ductus arteriosus. RESULTS: Accelerated villous maturation was associated with a decreased risk for Apgar score <7 at 5 min (p = 0.041). Fetal thrombosis and low placental weight were associated with an increased risk for both intrauterine fetal death (p < 0.001 and p = 0.011, respectively) and small-for-gestational age (p < 0.001 and p < 0.001, respectively). CONCLUSION: Placental histology may have prognostic value as it appears to be associated with intrauterine fetal death, as well as with being small-for-gestational age and assignment of a low Apgar score at birth.

Association between cerebral palsy and microscopically verified placental infarction in extremely preterm infants.

INTRODUCTION: Previously, cerebral palsy has been associated with placental infarctions diagnosed macroscopically by midwifes. However, the risk of misclassification of infarctionsis is high without a histological verification. Therefore, the objective of this study was to study placental histopathology in relation to developmental outcome at 2.5 years corrected age in a population born extremely preterm. MATERIAL AND METHODS: A prospective cohort study was carried out at Karolinska University Hospital, Stockholm, Sweden on a population of 139 live born infants delivered <27 gestational weeks during 2004-2007. A senior perinatal pathologist, who was blinded to outcome data, evaluated all placental slides microscopically. Neuromotor and sensory functions of the children were evaluated. Bayley Scales of Infant and Toddler Development-III (Bayley-III) were used to assess development at corrected age 2.5 years. The outcome data were evaluated without reference to obstetrical and pathology data. The primary outcome measure was neurological and developmental status at 2.5 years of corrected age. This was measured as diagnosis of cerebral palsy, visual impairment, hearing impairment as well as performance on Bayley-III scales evaluating cognitive, language and motor functions. RESULTS: Two out of seven children with placental infarction were diagnosed with cerebral palsy compared with one child of 51 without placental infarction (p = 0.036). For developmental outcome according to Bayley-III at 2.5 years no statistically significant associations with placental pathology were found. CONCLUSION: A possible association between placental infarction, verified by microscopic examination, and cerebral palsy has been identified in this extremely preterm population.

Neonatal blood transfusion as transmission route in chronic hepatitis C.

BACKGROUND: The aim of this study was to investigate if neonatal transfusions could underlie chronic hepatitis C in adults for whom the disease transmission route was previously unknown. STUDY DESIGN AND METHODS: Questionnaires were sent to 255 patients with chronic hepatitis C born in Sweden in 1960 to 1975. The medical records of 230 of the patients, of whom 98 (43%) had unknown transmission route, were studied regarding the occurrence of neonatal blood transfusions. The clinical, virologic, and histopathologic characteristics of those found to have received transfusions as neonates were also studied. RESULTS: Four of 230 (1.7%; 95% confidence interval, 0.5%-4.4%) patients with hepatitis C had received blood products as neonates. Three of them had reported unknown transmission route. One had cirrhosis, while two had mild histopathologic findings on liver biopsy. Three out of four patients in the transfused group, including the patient with liver cirrhosis, had undergone treatment for hepatitis C, all of them with a sustained viral response. CONCLUSION: Previously unidentified neonatal blood transfusions explain only a small fraction of chronic hepatitis C cases with unknown transmission route. Individual patients infected early in life can develop progressive liver damage as young adults and may benefit from antiviral treatment. The finding suggests that efforts are needed to actively trace and test adults who have been subjected to neonatal blood product transfusion before 1992.

Causes of stillbirth at different gestational ages in singleton pregnancies.

OBJECTIVE: To compare causes of stillbirth in preterm and term pregnancies. DESIGN: Cohort study. SETTING: All delivery wards in Stockholm, 1998-2009. POPULATION: Stillbirths from singleton pregnancies of gestational age ≥22(+0) (n = 1089) extracted from a web-based database including all stillbirths in the major Stockholm area since 1998. METHODS: The parents of the stillborns were all offered an extensive standardized investigation. The causes of death were assigned in a perinatal audit using the Stockholm classification of stillbirth. Singleton stillbirths were divided into preterm (gestational week 22(+0) -36(+6) ) and term/post-term (gestational week ≥37(+0) ). The term/post-term group was subdivided into term (gestational week 37(+0) -40(+6) ) and post-term stillbirths (gestational week ≥41(+0) ). MAIN OUTCOME MEASURE: Causes of stillbirth at different gestational ages. RESULTS: A higher proportion of placental abruption and preeclampsia/hypertension was seen in preterm stillbirths compared with term/post-term stillbirths, which instead had a higher proportion of umbilical cord complications and infection. Infection was more common in post-term than term stillbirths (46.5 vs. 19.8%, p < 0.001). CONCLUSION: Increased knowledge of causes of stillbirth in different gestational ages may be valuable in developing strategies for prevention of fetal death. The high proportion of infection in post-term stillbirths could be clinically important and warrants further studies.

Molecular and cytogenetic analysis in stillbirth: results from 481 consecutive cases.

INTRODUCTION: The underlying causes of stillbirth are heterogeneous and in many cases unexplained. Our aim was to conclude clinical results from karyotype and quantitative fluorescence-polymerase chain reaction (QF-PCR) analysis of all stillbirths occurring in Stockholm County between 2008 and 2012. By screening a subset of cases, we aimed to study the possible benefits of chromosomal microarray (CMA) in the analysis of the etiology of stillbirth. METHODS: During 2008-2012, 481 stillbirths in Stockholm County were investigated according to a clinical protocol including karyotype or QF-PCR analysis. CMA screening was performed on a subset of 90 cases, corresponding to all stillbirths from 2010 without a genetic diagnosis. RESULTS: Chromosomal aberrations were detected by karyotype or QF-PCR analysis in 7.5% of the stillbirths. CMA analysis additionally identified two known syndromes, one aberration disrupting a known disease gene, and 26 variants of unknown significance. Furthermore, CMA had a significantly higher success rate than karyotyping (100 vs. 80%, p < 0.001). DISCUSSION: In the analysis of stillbirth, conventional karyotyping is prone to failure, and QF-PCR is a useful complement. We show that CMA has a higher success rate and aberration detection frequency than these methods, and conclude that CMA is a valuable tool for identification of chromosomal aberrations in stillbirth.

Missed abortion in the 11-21-week period: Fetal autopsy and placental histopathological analysis of 794 cases.

INTRODUCTION: Missed abortion (MA) is a type of miscarriage with multiple etiological factors that refers to fetal death with a failure of the retained intrauterine product of conception to be discharged spontaneously. Currently fetal death in missed abortion is categorized according to three main causes: Fetal, placental, and maternal factors. The aim of the current study was to contribute and increase knowledge in clinical practice of late first and second trimester MA (Gestational age: week 11 + 0 - week 20 + 6). MATERIAL AND METHODS: This retrospective case series study includes 794 cases of fetuses and matching placentas sent to the Section of Perinatal Pathology, Department of Pathology, Karolinska Hospital between 2003 and 2019 from five different gynecology departments in the Stockholm region, Sweden. RESULTS: The cases were divided into two groups according to gestational length; gestational week 11 + 0-14 + 6 (group A) and 15 + 0-20 + 6 (group B) respectively, and comparisons were made between groups. Fetal growth restriction and placental pathology were more common in late MA, but number of cases with malformation were higher in early MA. Cord pathology was seen in approximately 40 % of the cases and equally distributed in the gestational weeks included. DISCUSSION: Fetal growth restriction and placental pathology were more common in late second trimester MA. This might demonstrate an early placental dysfunction affecting fetal growth and may be associated to maternal comorbidity such as autoimmune disease and cardiovascular disease. It is advisable to investigate maternal factors more closely after late second trimester MA before a future pregnancy. The risk for recurrent MA is believed to be low in cases of significant cord pathology. CONCLUSION: Cord complications were over-represented in missed abortion suggesting a probable etiopathogenetic link to fetal demise in this condition.

Placental pathology in a large (Swedish) cohort of SARS-CoV-2 infected mothers.

INTRODUCTION: SARS-CoV-2 placentitis is associated with placental destruction and insufficiency and can affect perinatal outcome. The aim of the current study was to contribute with increased knowledge regarding placental histology in maternal SARS-CoV-2 infection during the pregnancy, as well as the correlation to the severity of maternal SARS-CoV-2 infection. MATERIAL AND METHODS: This retrospective observational study included 116 women who had a verified SARS-CoV-2 infection during pregnancy and gave birth between April 2020 and February 2022 in the Stockholm region, Sweden. Placental tissue was evaluated regarding several histopathological parameters, amongst them detection of the triad of characteristics of placental SARS-CoV-2 infection: chronic histiocytic intervillositis, fibrin deposition and villous trophoblast necrosis, and immunohistochemistry for ORF-3 protein expression was used for confirmation. Medical records were reviewed for maternal characteristics and neonatal outcome. RESULTS: SARS-CoV-2 placentitis was present in one-fifth of the examined placentas admitted to the institute due to maternal SARS-CoV-2 infection, out of which 86,4 % were delivered by acute caesarian section (ACS), all on fetal indication, and one pregnancy ended in stillbirth. Half of the cases without placentitis were delivered by ACS, out of which 50 % were on fetal indication. There was a clear tendency of a shorter time gap between confirmed maternal SARS-CoV-2 infection and delivery in the placentitis group. DISCUSSION: The presence of SARS-CoV-2 placentitis does not seem to correlate with maternal factors or the severity of infection. It does correlate with development of placental dysfunction of acute/subacute onset and is often manifested as reduced fetal movements.

The phenotype range of achondrogenesis 1A.

Achondrogenesis 1A (ACG1A; OMIM 200600) is an autosomal recessive perinatally lethal skeletal dysplasia comprising intrauterine growth failure, micromelia, minor facial anomalies, deficient ossification of the skull, absent or extremely defective spinal ossification, short beaded ribs, and short deformed long bones with a stellate appearance. ACG1A is caused by mutations in the TRIP11 gene, resulting in deficiency of the Golgi microtubule associated protein 210. In this study we describe dizygotic twins with a clinical and radiological phenotype of ACG1A who were homozygous for a novel nonsense mutation in the TRIP11 gene. In addition, another patient with a milder manifestation, not readily distinguishable from those of other lethal skeletal dysplasias, was found to be a compound heterozygote for a nonsense mutation and a deletion of the 3' end of the TRIP11 gene. We conclude that mutations of the TRIP11 gene may encompass a wider phenotypic range than previously recognized.

Periprosthetic joint infection after total hip arthroplasty induces histological degeneration of the gluteus medius tendon.

Aims: A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient's quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach. Methods: A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed. Results: Biopsy samples from the GMED from infected patients revealed a larger fibril diameter than control patients, as seen in the TEM (p < 0.001). Uninfected patients were slightly older and had their revisions performed significantly later than the infected patients. Histologically, samples from infected patients revealed significantly more vascularity (p < 0.001), the presence of glycosaminoglycans (p < 0.001), and a higher TDS (p = 0.003) than the control patients. The majority of patients had staphylococcal infections of various species. Conclusion: More histological degeneration in the GMED was found in patients undergoing THA revision surgery due to PJI than in patients undergoing THA revision surgery due to other reasons.