B-type natriuretic peptide over N-terminal pro-brain natriuretic peptide to predict incident atrial fibrillation after cryptogenic stroke.

BACKGROUND AND PURPOSE: B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are well-known surrogates of atrial fibrillation (AF) detection but studies usually present data on either BNP or NT-proBNP. The aim was to determine and directly compare the validity of the two biomarkers as a tool to predict AF and guide prolonged cardiac monitoring in cryptogenic stroke patients. METHODS: Non-lacunar acute ischaemic stroke (<72 h) patients over 55 years of age with cryptogenic stroke after standard evaluation were included in the Crypto-AF study and blood was collected. BNP and NT-proBNP levels were determined by automated immunoassays. AF was assessed by 28 days' monitoring. Highest (optimizing specificity) and lowest (optimizing sensitivity) quartiles were used as biomarker cut-offs to build predictive models adjusted by sex and age. The integrated discrimination improvement index (IDI) and DeLong test were used to compare the performance of the two biomarkers. RESULTS: From 320 patients evaluated, 218 were included in the analysis. AF was detected in 50 patients (22.9%). NT-proBNP (P < 0.001) and BNP (P < 0.001) levels were higher in subjects with AF and their levels correlated (r = 0.495, P < 0.001). BNP showed an increased area under the curve (0.720 vs. 0.669; P = 0.0218) and a better predictive capacity (IDI = 3.63%, 95% confidence interval 1.36%-5.91%) compared to NT-proBNP. BNP performed better than NT-proBNP in a specific model (IDI = 3.7%, 95% confidence interval 0.87%-6.5%), whilst both biomarkers performed similarly in the case of a sensitive model. CONCLUSIONS: Both BNP and NT-proBNP were increased in cryptogenic stroke patients with AF detection. Interestingly, BNP outperforms NT-proBNP, especially in terms of specificity.

Large vessel occlusion is independently associated with atrial fibrillation detection.

BACKGROUND AND PURPOSE: Covert paroxysmal atrial fibrillation (pAF) is the most frequent cause of cardiac embolism. Our goal was to discover parameters associated with early pAF detection with intensive cardiac monitoring. METHOD: Crypto-AF was a multicentre prospective study (four Comprehensive Stroke Centres) to detect pAF in non-lacunar cryptogenic stroke continuously monitored within the first 28 days. Stroke severity, infarct pattern, large vessel occlusion (LVO) at baseline, electrocardiography analysis, supraventricular extrasystolia in the Holter examination, left atrial volume index and brain natriuretic peptide level were assessed. The percentage of pAF detection and pAF episodes lasting more than 5 h were registered. RESULTS: Out of 296 patients, 264 patients completed the monitoring period with 23.1% (61/264) of pAF detection. Patients with pAF were older [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08], they had more haemorrhagic infarction (OR 4.03, 95% CI 1.44-11.22), they were more likely to have LVO (OR 4.29, 95% CI 2.31-7.97) (P < 0.0001), they had a larger left atrial volume index (OR 1.03, 95% CI 1.01-1.1) (P = 0.0002) and they had a higher level of brain natriuretic peptide (OR 1.01, 95% CI 1.0-1.1). Age and LVO were independently associated with pAF detection (OR 1.06, 95% CI 1.00-1.16, and OR 4.58, 95% CI 2.27- 21.38, respectively). Patients with LVO had higher cumulative incidence of pAF (log rank P < 0.001) and more percentage of pAF > 5 h [29.6% (21/71) vs. 8.3% (12/144); OR 4.62, 95% CI 2.11-10.08; P < 0.001]. In a mean follow-up of 26.82 months (SD 10.15) the stroke recurrence rate was 4.6% (12/260). CONCLUSIONS: Large vessel occlusion in cryptogenic stroke emerged as an independent marker of pAF.

Primary Langerhans Cell Histiocytosis in Thyroid.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare group of neoplastic diseases resulting from Langerhans dendritic cells. The most common site (80%) is bones. Thyroid gland involvement is exceedingly rare and usually expected to be seen as a part of multisystemic disease. CASE REPORT: We present a 45 year old male patient operated due to multinodular goiter and neck pain, and diagnosed with LCH in his postoperative pathologic examination. As a result of the systemic screening performed after the pathological diagnosis, the disease was interestingly localized to the thyroid gland. Systemic involvement did not develop in the two-year follow-up of the patient who did not receive additional chemotherapy treatment. CONCLUSION: It is difficult to diagnose LCH in the thyroid gland before surgery. Although surgical treatment with or without chemotherapy is recommended, surgery is not recommended alone since it is generally systemic involvement. However, in primary thyroid LCH cases limited to the thyroid gland, we recommend that only total thyroidectomy treatment should be kept in mind.

Hip hemiarthroplasty for femur neck fractures: minimally invasive direct anterior approach versus postero-lateral approach.

BACKGROUND: The minimally invasive direct anterior approach (MDAA) has been reported to be useful in total hip arthroplasty. The benefits of this approach may be useful for the treatment of femoral neck fractures. Aim of this study is to compare MDAA and postero-lateral approach (PLA) in patients treated with hip hemiarthroplasty for femoral neck fractures. MATERIALS AND METHODS: Between 2013 and 2014, 109 patients underwent bipolar hip hemiarthroplasty for femoral neck fracture: 88 female and 21 male with a mean age of 88 years old. PLA was performed in 54 cases and MDAA in 55 cases. RESULTS: The mean surgery time was significantly lower in MDAA group (P = 0.001). The hemoglobin loss was significantly lower in MDAA group (P = 0.02). The mean postoperative pain was significantly lower in the MDAA group (P = 0.001). The mean hospitalization period was 2 days lower in the MDAA group but with no significant difference between the two groups (P = 0.09). Hip dislocation was higher in PLA cases (7.4 %) than in MDAA cases (1.8 %). Periprosthetic fracture occurred only in one case of PLA. Great trochanter fracture occurred in 1 MDAA cases, while no cases were observed in the PLA group. CONCLUSIONS: Minimally invasive direct anterior approach for hip hemiarthroplasty in elderly people with femoral neck fracture provided significant benefit in the early postoperative period when compared to the postero-lateral approach in terms of surgery time, hemoglobin loss, postoperative pain, time of recovery and dislocation rate. LEVEL OF EVIDENCE: Therapeutic study, level IV (case series).

The effects of sunitinib on endometriosis.

The aim of the present study was to evaluate the effect of sunitinib on endometriotic implants and adhesions in a rat endometriosis model. An experimental endometriosis model was created in 21 rats. These rats were randomly divided into three groups: Group 1 (control group, 7 rats) was given no medication; Group 2 (sunitinib group, 7 rats) was given 3 mg/kg per day of oral sunitinib; and Group 3 (danazol group, 7 rats) was given 7.2 mg/kg per day of oral danazol. The volume of endometriotic implants was calculated. The extent and severity of adhesions were evaluated. The groups were compared by the Student's t-test, analysis of variance (ANOVA) and the Mann-Whitney U test. There was no statistically significant difference in the mean volume of endometriotic implants before medication between three groups. The volume of implants and extent, severity, total score of adhesions were significantly decreased after medication in Group 2 and Group 3. We noted that the volume of the endometriotic implants and adhesion formation were decreased both after sunitinib and danazol treatment. As a result, sunitinib seems to be effective for endometriotic peritoneal lesions. The effects of sunitinib in rat models give hope for improving the treatment of human endometriosis and prevention of pain symptoms.

Significance of TNM staging, Demographic and Histologic Features in Predicting the Prognosis of Renal Cell Carcinoma.

BACKGROUND: The aim of this study was to evaluate the prognostic significance of clinical, demographic and detailed histopathological parameters in renal cell carcinoma (RCC). METHODS: A total of 102 patients who underwent partial or radical nephrectomy for a renal mass between 2008 and 2013 were evaluated retrospectively. Fuhrman grade, TNM stage, macroscopic satellite tumor nodule formation, histopathological subtype, renal vein invasion (RVI), necrosis, microvessel invasion (MVI), sarcomatoid differentiation and overall survival (OS) were evaluated to determine prognostic factors. RESULTS: The 102 patients consisted of 73 with clear cell tumor, 15 with papillary tumor, 12 with chromophobe tumor and 2 collecting duct RCC cases. A statistically negative relationship was observed between increasing age and OS when the patients were grouped as above and under 40 years of age. There was no statistical relationship between OS and histopathological subtype, adrenal gland invasion, and lymph node metastasis. The risk of death was 10-fold increased in patients with stage 4 tumor compared to patients with stage 1 tumor. Statistically significant macroscopical parameters for OS were satellite tumor nodule presence, Fuhrman grade, tumor size, renal sinus and perinephric fat invasion, distant metastasis, and RVI. The risk of death was 13-fold higher in cases with sarcomatoid differentiation. There was a strong correlation between the presence of a satellite tumor nodule, necrosis, sarcomatoid differentiation and the tumor stage. A statistically negative correlation was observed between OS and the MVI, sarcomatoid differentiation, and necrosis. CONCLUSION: We found the Fuhrman grade, tumor size, renal sinus and perinephric fat invasion, distant metastasis, RVI, MVI, sarcomatoid differentiation, necrosis and satellite tumor nodule to be all statistically significant parameters for OS. The addition of other variables to the TNM stage and grade may improve the prediction of outcomes for RCC patients.

Survival of current production tumor endoprostheses: complications, functional results, and a comparative statistical analysis.

BACKGROUND AND OBJECTIVES: Retrospectively analyze outcomes of current-generation Global Modular Replacement System (GMRS) modular tumor endoprosthesis for the lower limb in primary and secondary implantation procedures. METHODS: Two hundred ninety five prostheses were implanted, 197 were primary implants, 98 were for revision surgery; revision procedures included 84 failed tumor reconstructions and 14 failed non-tumor reconstructions. Anatomic sites included: distal femur 199; proximal tibia 60; proximal femur 32;total femur 4. Endoprosthesis failures were classified as soft-tissue failures (Type 1), aseptic loosening (Type 2), structural fracture (Type 3), infection (Type 4), and tumor recurrence (Type 5). MSTS functional scores were measured. RESULTS: The overall failure rate was 28.8% and failure occurred at a median of 1.7 years (range, 1 month to 7 years). At a mean oncologic follow up of 4.2 years (range, 2-8 years), 195 patients are continuously NED, 43 NED after treatment of relapse, 10 AWD, 33 DWD. There was a significant difference in implant survival of all modes of failure between primary and revision implants (P = 0.03). No prosthetic fracture occurred. The average functional score was 81.6% (24.5). CONCLUSIONS: Mid-term results with GMRS are promising, with good functional results and low incidence of complications for primary implants. LEVEL OF EVIDENCE: Therapeutic study, level IV-1 (case series).

Cemented versus cementless endoprostheses for lower limb salvage surgery.

PURPOSE: To determine the survival and failures of cemented vs cementless endoprostheses. METHODS: We retrospectively studied 232 patients treated with lower limb salvage surgery and reconstruction using cementless and cemented endoprostheses from 2002 to 2007. We compared survival and failures of the endoprostheses regarding age, gender, body mass index (BMI), diagnosis, site of reconstruction, radiation therapy, chemotherapy, and stem fixation. RESULTS: The mean patient follow-up was 28 months (median 24; range 12-84). The overall survival of cemented and cementless endoprostheses at 60 months was 64 and 78%, respectively (p=0.0078). Survival at 60 months of cemented and cementless endoprostheses to infection was 68 and 82%, respectively (p=0.0248). Survival of cemented and cementless endoprostheses to aseptic loosening at 60 months was 94 and 96%, respectively (p=0.1493). The only significant univariate and multivariate predictor of survival was the cementless type of stem fixation. CONCLUSION: Cementless endoprostheses have higher overall survival and survival to infection compared to cemented endoprostheses. Survival to aseptic loosening is not different. Stem fixation is the only significant variable for survival.

Expandable tumor prostheses in children.

Any surgical resection in the lower extremities in children will cause a leg length discrepancy from physeal resection. To avoid the resulting functional deficit, leg length discrepancy must be reconciled with surgical techniques to approximate equal leg lengths at skeletal maturity. Currently there are several manufacturers who offer options for prosthetic reconstruction with expandable implants. These implants can be expanded to a length projected on the basis of three factors: the length of bone resected, the anticipated future growth of the contralateral extremity, and the estimated discrepancy of limb length at skeletal maturity. In this article, we review the basic principles and guidelines for prediction of remaining bone growth and planning lengthening in children, and present the currently available expandable prostheses and the evolution performed over time.

Linkage analysis and a novel COL4A5 mutation in a large Turkish family with Alport syndrome.

BACKGROUND: Alport syndrome (AS) is a renal disease that is characterized by proteinuria and progressive renal failure, and often accompanied by sensorineural hearing loss and ocular changes. Mutations in the genes encoding for three members of the type IV collagen protein family have been found to be the cause of the disease. We describe a large Turkish family with X-linked AS. We performed linkage analysis in this family and sequencing to identify the mutation in the proband whose disease was confirmed by renal biopsy. METHODS: After genomic DNAs extracted, linkage to the COL4A5 locus was examined using the 2B6 and 2B20, DXS1106, DXS1105 and COL4A5 markers. In addition, COL4A5 gene sequence analysis was performed in the proband. RESULTS: Genetic linkage analysis demonstrated co-segregation of the disease. Haplotype analysis showed that the same haplotype was carried by all affected males and obligatory carrier females. Mutation analysis of the proband has revealed a novel nonsense mutation (c.1135C>T; Gln379X) in exon 19 of the COL4A5 gene which may lead to a more severe phenotype in affected family members carrying this mutation. According to GenBank data base, this mutation has not been reported previously. CONCLUSION: Genetic testing identified a previously undescribed COL4A5 mutation as the cause of the disease.

SRY gene amplifications and genotypings revealed the occurrence of the hidden maternal decidual cells in 46,XX karyotyped spontaneous abortions.

Reports of abnormal karyotypes or normal 46,XY karyotypes of the abortion materials derivated from tissue cultures are mostly addressing the pregnancy loss tissues. The accuracy of the cytogenetic reports of normal 46,XX karyotypes is obscure, as the results may reflect the normal karyotyped female pregnancy losses or the hidden maternal decidual cells covering the cytogenetically normal or abnormal male or female products of conception. In the present study, thirty-eight 46,XX normal karyotyped abortion materials cultivated from villi were re-analysed for excluding maternal cell contamination by using molecular approaches in an accurate algorithm. Abortion materials DNAs were amplified by polymerase chain reaction (PCR) technique in order to search the products of the sex determinating region gene of chromosome Y (SRY). Sixteen out of 38 abortion materials revealed Y-chromosome component (42.1%). Amplification negative DNAs and their parental DNAs were genotyped by using high-polymorphic microsatellite DNA markers to identify the origin of the components of the chromosome X. Maternal chromosome X components were detected in 18 (81.8%). As a result, SRY amplifications and genotypings ascertained the high rate of maternal decidual cells in 46,XX products of conception.

COVID-19 strategy in organizing and planning orthopedic surgery in a major orthopedic referral center in an area of Italy severely affected by the pandemic: experience of the Department of Orthopedics, University of Padova.

BACKGROUND: According to the required reorganization of all hospital activities, the recent COVID-19 pandemic had dramatic consequences on the orthopedic world. We think that informing the orthopedic community about the strategy that we adopted both in our hospital and in our Department of Orthopedics could be useful, particularly for those who are facing the pandemic later than Italy. METHODS: Changes were done in our hospital by medical direction to reallocate resources to COVID-19 patients. In the Orthopedic Department, a decrease in the number of beds and surgical activity was stabilized. Since March 13, it has been avoided to perform elective surgery, and since March 16, non-urgent outpatient consultations were abolished. This activity reduction was associated with careful evaluation of staff and patients: extensive periodical swab testing of all healthcare staff and swab testing of all surgical patients were applied. RESULTS: These restrictions determined an overall reduction of all our surgical activities of 30% compared to 2019. We also had a reduction in outpatient clinic activities and admissions to the orthopedic emergency unit. Extensive swab testing has proven successful: of more than 160 people tested in our building, only three COVID-19 positives were found, and of over more than 200 surgical procedures, only two positive patients were found. CONCLUSIONS: Extensive swab test of all people (even if asymptomatic) and proactive tracing and quarantining of potential COVID-19 positive patients may diminish the virus spread.

Infection in orthopaedic oncology: crucial problem in modern reconstructive techniques.

OBJECTIVE: Infection after orthopaedic oncology surgery is a relatively frequent complication. Infection rate ranges in the literature between 3.7% and 19.9%, increasing up to 47% after pelvic resection and reconstruction. It represents a challenging topic when occurring in oncologic patients because of the delay of systemic and local treatments, influencing prognosis. Infection is a major concern in terms of both prevention and treatment. The aim of our review was to analyze data reported in the literature about strategies and new materials for infection prevention in musculoskeletal oncology surgery. MATERIALS AND METHODS: We reviewed the literature focusing on the use of new materials that can reduce the risk of infection, avoiding biofilm formation on the implant surface. RESULTS AND DISCUSSION: New materials are available to try to reduce the risk of infection. Iodine-coating, DAC-coating or silver-coating, are the more promising technologies available at today. Initial results with DAC-coating in non-oncological patients are interesting; however, studies about its efficacy in preventing infection in orthopaedic oncology are not present in literature. On the other side, iodine-coating implants or silver-coating prostheses demonstrated efficacy against early infections, associated with lower risk of implant removal and amputation as final surgery. CONCLUSIONS: Post-operative infections in orthopaedic oncology surgery are still frequent, and their diagnosis and treatment are demanding. According to the literature, silver-coated prostheses should be considered as the best option in case of revision surgery due to infection. However, there is no evidence that these new materials are effective to decrease the risk of infection drastically. Further studies with numerous series and long-term follow up are required.

Intrahepatic cholangiocarcinoma arising in chronic viral hepatitis-associated cirrhosis: two transplant cases.

Hepatitis C virus (HCV) or hepatitis B virus (HBV)-related cirrhosis is known to be a risk factor for hepatocellular carcinoma (HCC). Recently, these viruses have been reported to have an etiologic role in the development of intrahepatic cholangiocarcinoma (ICC). Herein we have reported two cases of HCV- and HBV-related cirrhosis with ICC in whom the pretransplant diagnosis was HCC. The patient with HCV cirrhosis, was a 47-year-old woman with a large nodule in the right lobe. The patient with HBV cirrhosis was a 45-year-old man with two nodules. Serum tumor marker levels, carcinoembryonic antigen (CEA), alphafetoprotein (AFP), and carbohydrate antigen 19-9 (CA 19-9) were determined before live donor liver transplantation (LDLT). The patient with HCV cirrhosis showed mildly elevated serum levels of AFP. The patient with HBV cirrhosis showed an elevated CA 19-9 level. On microscopic examination, all nodules exhibited typical morphological findings of adenocarcinoma. The patient with HCV cirrhosis developed brain metastases 4 years after LDLT. The patient with HBV cirrhosis is disease-free at 18 months after transplantation. In cirrhotic patients with active malignancy who are candidates for LDLT, ICC should be considered in the differential diagnosis. Although the literature is limited, selected patients with ICC may benefit from LDLT.

A boy with small supernumerary marker chromosome X identified by FISH.

Marker or ring X chromosomes are frequently seen in Ullrich-Turner Syndrome with 46,X,r(X) karyotype, but only 8 children were reported with an extra marker X chromosome in at least some of their cell lines, we describe a 5 years old male patient who is mosaic (17%) for a cell line with an extra ring shaped marker X chromosome in addition to a normal 46,XY cell line. He had mild motor mental retardation, a dysmorphic face, dysplastic ears, high arched palate, cryptorchidism and brachydactyly. G-banding showed 46,XY[83]/47,XY,+r?[17] karyotype. NOR banding revealed no satellite region but its centromere was intact in C-banding. By fluorescent in situ hybridization (FISH) technique, dual X/Y alpha-satellite probes were used to detect the origin of ring shaped marker chromosome and 17% of his cells had two X chromosome signals due to marker X; hybridization with X chromosome inactivation center (XIST) specific probe revealed the absence of the locus on the ring chromosome. In this report, clinical features of our patient are compared with previously reported cases and the cytogenetic and molecular cytogenetic techniques used to detect origin of marker chromosome are discussed.

Transposition of great arteries in an infant born after prenatal diagnosis of trisomy 20 mosaicism.

We report a case of prenatally diagnosed mosaic trisomy 20 in cells cultured from amniotic fluid. Trisomy 20 was present in 7 cells (13 percent) in a total of 52 investigated cells. Following the normal findings of an ultrasound scan, the couple decided to continue the pregnancy. A dysmorphic infant was born at the 38 weeks of gestation with generalized dysmorphic features and multiple cardiac anomalies including transposition of great arteries. Chromosome analysis on both cord blood and placenta at birth revealed a normal 46,XX karyotype. This patient is the first case of a liveborn infant with mosaic trisomy 20 cells detected in amniotic fluid culture with transposition of great arteries, atrioventricular concordance and ventricoarterial discordance.

Megaprosthesis of the knee in tumor and revision surgery.

The introduction of multidisciplinary approach with chemo and radiotherapy, the advances in surgical and the improvements of diagnostic techniques allowed limb salvage surgery in most cases of bone sarcomas instead of amputation. Modular megaprostheses are the most common method of reconstruction after segmental resection of the long bones in the extremities for their availability, immediate fixation, early weight bearing, good function. Despite the advances in materials and implant designs, these systems have an high incidence of complications. Aim of this study was to report the experience on mega-prostheses implanted around the knee in tumor and revision surgery to analyze: the most frequent used current systems, the problems of stems fixation, extensor mechanism reconstructions in proximal tibia resections and the preservation of growth of the lower extremity in children.

The stability of the hip after the use of a proximal femoral endoprosthesis for oncological indications: analysis of variables relating to the patient and the surgical technique.

AIMS: Instability of the hip is the most common mode of failure after reconstruction with a proximal femoral arthroplasty (PFA) using an endoprosthesis after excision of a tumour. Small studies report improved stability with capsular repair of the hip and other techniques, but these have not been investigated in a large series of patients. The aim of this study was to evaluate variables associated with the patient and the operation that affect post-operative stability. We hypothesised an association between capsular repair and stability. PATIENTS AND METHODS: In a retrospective cohort study, we identified 527 adult patients who were treated with a PFA for tumours. Our data included demographics, the pathological diagnosis, the amount of resection of the abductor muscles, the techniques of reconstruction and the characteristics of the implant. We used regression analysis to compare patients with and without post-operative instability. RESULTS: A total of 20 patients out of 527 (4%) had instability which presented at a mean of 35 days (3 to 131) post-operatively. Capsular repair was not associated with a reduced rate of instability. Bivariate analysis showed that a posterolateral surgical approach (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.02 to 0.86) and the type of implant (p = 0.046) had a significant association with reduced instability; age > 60 years predicted instability (OR 3.17, 95% CI 1.00 to 9.98). Multivariate analysis showed age > 60 years (OR 5.09, 95% CI 1.23 to 21.07), female gender (OR 1.73, 95% CI 1.04 to 2.89), a malignant primary bone tumour (OR 2.04, 95% CI 1.06 to 3.95), and benign condition (OR 5.56, 95% CI 1.35 to 22.90), but not metastatic disease or soft-tissue tumours, predicted instability, while a posterolateral approach (OR 0.09, 95% CI 0.01 to 0.53) was protective against instability. No instability occurred when a synthetic graft was used in 70 patients. CONCLUSION: Stability of the hip after PFA is influenced by variables associated with the patient, the pathology, the surgical technique and the implant. We did not find an association between capsular repair and improved stability. Extension of the tumour often dictates surgical technique; however, our results indicate that PFA using a posterolateral approach with a hemiarthroplasty and synthetic augment for soft-tissue repair confers the lowest risk of instability. Patients who are elderly, female, or with a primary benign or malignant bone tumour should be counselled about an increased risk of instability. Cite this article: Bone Joint J 2017;99-B:531-7.