Changes in operative treatment of tibia fractures in Finland between 2000 and 2018: A nationwide study.

INTRODUCTION: Incidences of different tibia fractures are not well reported. Possible changes in the operative treatment methods have also not been studied. The aim of this nationwide registry study is to determine the incidence of operatively treated tibia fractures and investigate the possible changes in treatment methods in Finland between 2000 and 2018. METHODS: All patients aged 16 years or older with operatively treated tibia fractures in Finland from 2000 to 2018 were included. The incidence of operatively treated proximal, diaphyseal, and distal tibia fractures per 100,000 person years by age, sex, mechanism of injury, and study year was calculated. Data were extracted from the Finnish National Hospital Discharge Register. RESULTS: A total of 5996 proximal, 6874 diaphyseal, and 5658 distal tibia fractures were reported during the 18-year study period, resulting in incidences of 7.2/100,000, 8.1/100,000, and 6.9/100,000 person years for operatively treated proximal, diaphyseal, and distal tibia fractures, respectively. Over the study period, a clear change in fixation method in distal tibia fractures was found as plating became popular in the beginning of the 21st century. During the last 5 years of the study period, nailing and plating were equally used. CONCLUSIONS: Operatively treated proximal tibia fractures are most common among older females while diaphyseal fractures are most frequent in young male patients. Distal tibia fractures occur most often among middle-aged people.

Flexural and torsional properties of a glass fiber-reinforced composite diaphyseal bone model with multidirectional fiber orientation.

Although widely used, metallic implants have certain drawbacks in reconstructive bone surgery. Their high stiffness in respect to cortical bone can lead to complications which include periprosthetic fractures and aseptic loosening. In contrast to metallic alloys, fiber-reinforced composites (FRC) composed of a thermoset polymer matrix reinforced with continuous E-glass fibers have elastic properties matching those of bone. We investigated the mechanical properties of straight FRC tubes and FRC bone models representing the diaphysis of rabbit femur prepared from glass fiber/bisphenol A glycidyl methacrylate (BisGMA) - triethylene glycol dimethacrylate (TEGDMA) composite in three-point bending and torsion. Three groups of straight FRC tubes with different fiber orientations were mechanically tested to determine the best design for the FRC bone model. Tube 1 consisted most axially oriented unidirectional fiber roving and fewest bidirectional fiber sleevings. Fiber composition of tube 3 was the opposite. Tube 2 had moderate composition of both fiber types. Tube 2 resisted highest stresses in the mechanical tests and its fiber composition was selected for the FRC bone model. FRC bone model specimens were then prepared and the mechanical properties were compared with those of cadaver rabbit femora. In three-point bending, FRC bone models resisted 39-54% higher maximum load than rabbit femora with similar flexural stiffness. In torsion, FRC bone models resisted 31% higher maximum torque (p < 0.001) and were 38% more rigid (p = 0.001) than rabbit femora. Glass fiber-reinforced composites have good biocompatibility and from a biomechanical perspective, they could be used even in reconstruction of segmental diaphyseal defects. Development of an implant applicable for clinical use requires further studies.

High-throughput transcriptomic and RNAi analysis identifies AIM1, ERGIC1, TMED3 and TPX2 as potential drug targets in prostate cancer.

Prostate cancer is a heterogeneous group of diseases and there is a need for more efficient and targeted methods of treatment. In this study, the potential of gene expression data and RNA interference technique were combined to advance future personalized prostate cancer therapeutics. To distinguish the most promising in vivo prevalidated prostate cancer drug targets, a bioinformatic analysis was carried out using genome-wide gene expression data from 9873 human tissue samples. In total, 295 genes were selected for further functional studies in cultured prostate cancer cells due to their high mRNA expression in prostate, prostate cancer or in metastatic prostate cancer samples. Second, RNAi based cell viability assay was performed in VCaP and LNCaP prostate cancer cells. Based on the siRNA results, gene expression patterns in human tissues and novelty, endoplasmic reticulum function associated targets AIM1, ERGIC1 and TMED3, as well as mitosis regulating TPX2 were selected for further validation. AIM1, ERGIC1, and TPX2 were shown to be highly expressed especially in prostate cancer tissues, and high mRNA expression of ERGIC1 and TMED3 associated with AR and ERG oncogene expression. ERGIC1 silencing specifically regulated the proliferation of ERG oncogene positive prostate cancer cells and inhibited ERG mRNA expression in these cells, indicating that it is a potent drug target in ERG positive subgroup of prostate cancers. TPX2 expression associated with PSA failure and TPX2 silencing reduced PSA expression, indicating that TPX2 regulates androgen receptor mediated signaling. In conclusion, the combinatorial usage of microarray and RNAi techniques yielded in a large number of potential novel biomarkers and therapeutic targets, for future development of targeted and personalized approaches for prostate cancer management.

Classification of unknown primary tumors with a data-driven method based on a large microarray reference database.

We present a new method to analyze cancer of unknown primary origin (CUP) samples. Our method achieves good results with classification accuracy (88% leave-one-out cross validation for primary tumors from 56 categories, 78% for CUP samples), and can also be used to study CUP samples on a gene-by-gene basis. It is not tied to any a priori defined gene set as many previous methods, and is adaptable to emerging new information.

Alignment of gene expression profiles from test samples against a reference database: New method for context-specific interpretation of microarray data.

BACKGROUND: Gene expression microarray data have been organized and made available as public databases, but the utilization of such highly heterogeneous reference datasets in the interpretation of data from individual test samples is not as developed as e.g. in the field of nucleotide sequence comparisons. We have created a rapid and powerful approach for the alignment of microarray gene expression profiles (AGEP) from test samples with those contained in a large annotated public reference database and demonstrate here how this can facilitate interpretation of microarray data from individual samples. METHODS: AGEP is based on the calculation of kernel density distributions for the levels of expression of each gene in each reference tissue type and provides a quantitation of the similarity between the test sample and the reference tissue types as well as the identity of the typical and atypical genes in each comparison. As a reference database, we used 1654 samples from 44 normal tissues (extracted from the Genesapiens database). RESULTS: Using leave-one-out validation, AGEP correctly defined the tissue of origin for 1521 (93.6%) of all the 1654 samples in the original database. Independent validation of 195 external normal tissue samples resulted in 87% accuracy for the exact tissue type and 97% accuracy with related tissue types. AGEP analysis of 10 Duchenne muscular dystrophy (DMD) samples provided quantitative description of the key pathogenetic events, such as the extent of inflammation, in individual samples and pinpointed tissue-specific genes whose expression changed (SAMD4A) in DMD. AGEP analysis of microarray data from adipocytic differentiation of mesenchymal stem cells and from normal myeloid cell types and leukemias provided quantitative characterization of the transcriptomic changes during normal and abnormal cell differentiation. CONCLUSIONS: The AGEP method is a widely applicable method for the rapid comprehensive interpretation of microarray data, as proven here by the definition of tissue- and disease-specific changes in gene expression as well as during cellular differentiation. The capability to quantitatively compare data from individual samples against a large-scale annotated reference database represents a widely applicable paradigm for the analysis of all types of high-throughput data. AGEP enables systematic and quantitative comparison of gene expression data from test samples against a comprehensive collection of different cell/tissue types previously studied by the entire research community.

Arachidonic acid pathway members PLA2G7, HPGD, EPHX2, and CYP4F8 identified as putative novel therapeutic targets in prostate cancer.

The arachidonic acid and prostaglandin pathway has been implicated in prostate carcinogenesis, but comprehensive studies of the individual members in this key pathway are lacking. Here, we first conducted a systematic bioinformatic study of the expression of 36 arachidonic acid pathway genes across 9783 human tissue samples. The results showed that the PLA2G7, HPGD, EPHX2, and CYP4F8 genes are highly expressed in prostate cancer. Functional studies using RNA interference in prostate cancer cells indicated that all four genes are also essential for cell growth and survival. Clinical validation confirmed high PLA2G7 expression, especially in ERG oncogene-positive prostate cancers, and its silencing sensitized ERG-positive prostate cancer cells to oxidative stress. HPGD was highly expressed in androgen receptor (AR)-overexpressing advanced tumors, as well as in metastatic prostate cancers. EPHX2 mRNA correlated with AR in primary prostate cancers, and its inhibition in vitro reduced AR signaling and potentiated the effect of antiandrogen flutamide in cultured prostate cancer cells. In summary, we identified four novel putative therapeutic targets with biomarker potential for different subtypes of prostate cancer. In addition, our results indicate that inhibition of these enzymes may be particularly powerful when combined with other treatments, such as androgen deprivation or induction of oxidative stress.

[Changing aspects of cirrhotic disease in a hepato-gastroenterology service in Mali]. / Aspects evolutifs de la maladie cirrhotique dans un service d'hepato gastro enterologie au Mali.

The main goal of our study was to evaluate cirrhosis course on one year. The study was prospective and longitudinal from January 2005 to December 2006 in the center of hepatology and gastro-enterology of CHU Gabriel Touré. The patients had one year follow up and examinated every three months. In this study 57 patients were included. Mean age was 41,5 + 15,3 years. Ascite and jaundice were the main clinical signs respectively 70.2% and 54.4%. Ascite or its increase was the most complication in 67.5% of cases (p = 0.002). The global mortality was 82.5% and it was high in the three first months, caused by hepatocellular carcinoma, digestive bleeding and hepatic encephalopathy respectively 33.3%, 27.3% and 15.2%. Abdomen pain, ascite and jaundice have an predictive value for high mortality (p between 3.10-3 et 10-7). Early examination, therapeutic observance and good management of cirrhosis complications could reduce the mortality.

Aspects évolutifs de la maladie cirrhotique dans un service d'hépato gastro-entérologie au Mali

Le but principal de notre étude était d'évaluer l'évolution de la maladie cirrhotique à un an de suivi. Il s'agissait d'une étude prospective et longitudinale de Janvier 2005 à Décembre 2006 dans le service d'Hépato Gastroentérologie du CHU Gabriel TOURE. Les malades ont bénéficié d'un suivi d'un an au cours duquel ils ont été vus en consultation tous les 3 mois. Au terme de l'étude 57 malades ont été colligés. L'âge moyen des patients était de 41,5 + 15,3 ans. L'ascite a été le motif de consultation dans près de la moitié des cas (49,1%). L'ascite et l'ictère étaient les signes les plus retrouvés à l'examen physique avec respectivement 70,2% et 54,4%. L'apparition ou l'aggravation d'une ascite a été la complication la plus retrouvée au cours de l'année avec 67,5% des cas (p = 0,002). La mortalité globale a été de 82,5% et surtout élevée au cours des trois premiers mois, due en majorité au CHC, à l'hémorragie digestive et l'encéphalopathie hépatique avec respectivement 33,3%, 27,3% et 15,2%. La douleur abdominale, l'ascite et l'ictère ont une valeur prédictive de mortalité élevée (p compris entre 3.10 -3 et 10 -7). Une consultation précoce, une observance thérapeutique et une prise en charge correcte des complications de la cirrhose pourraient réduire cette mortalité

[Gastrointestinal hemorrhage caused by esophageal varix rupture]. / Hemorragies digestives par rupture de varices oesophagiennes.

UNLABELLED: The aim of this study was to analyze digestive hemorrhage by oesophageal varicose vein bleeding, were pharmacological and endoscopic treatments suitable are not available. PATIENTS: This prospective study related to 50 patients admitted for oesophageal varicose vein bleeding in the service of hepato-gastro-enterology of the hospital Gabriel Touré (MALI), from June 2003 to December 2005. METHODS: The patients underwent clinical examination and upper digestive endoscopy to appreciate oesophageal varicose vein and marks of bleeding. Some biological examinations (haemoglobin, hematocrit, prothrombin time) were carried out in emergency to appreciate systemic repercussion of the haemorrhage. RESULTS: Our results showed that by oesophageal varicose vein bleeding represented 2.5% of the hospitalizations during the period of study.The average age of the patients was 37 years with, a sex ratio of 6.1% in favour of men. Antecedent of jaundice was frequently found (54%). The main cause of the varicose vein was cirrhosis. Mortality was 48%. The prognosis was not significantly improved by blood transfusion. CONCLUSION: At the end of this study, the stress must be laid on the HBV prevention because HBV is the main cause of chronic liver diseases.

[Gastritis associated with duodeno-gastric reflux]. / Gastrite chronique et reflux duodeno-gastrique.

Our main objective was to study gastritis associated to duodeno-gastric reflux. It is about a longitudinal study case/witness, paired according to the sex and the age. It was unrolled from February 2005 to January 2006 in the digestive diseases department of the hospital Gabriél Touré, and endoscopic centers of Promenade des Angevins, and clinique Farako. The patients profited from an upper digestive endoscopy to appreciate endoscopic aspect of gastritis associated to bile in the stomach mucus lake. The gastric biopsies were systematic. This study included 50 patients having gastritis associated to bile in gastric mucus lake compared to 50 patients having gastritis associated to clearly gastric mucus lake. The sex-ratio was 1.26 in favour of men. The average age of the patients was of 41.30 +/- 15.43 years. On the symptomatic hand, fetid breath was significantly met in duodeno-gastric reflux (p = 0.013). Potash consumption in the "tô" (millet cake) was significantly reported in gastritis associated to bile in gastric mucus lake (p = 0.042). The endoscopic aspects were comparable. Histological aspects of nonatrophic chronic gastritis were significantly mint in witnesses as well into the antrum as into the fundus (p = 0.0001 and p = 0.00023). The reactional gastritis aspect was the prerogative of duodenogastric reflux (p ranging between 10(-6) and 3.10 (-6). Helicobacter pylori infection was found comparable in the two groups (p = 0.297). Dysplasia although rare was found only in gastritis associated to duodeno-gastric reflux. Gastritis associated to bile in gastric mucus does not se,nm to have specific clinical, endoscopic and histological presentation. However the presence of dysplasia must have an attentive monitoring.

[Evaluation of hospitalizations in the gastroenterology service of Gabriel Toure Hospital, Mali]. / Evaluation des hospitalisations dans un service de medecine: cas du service d'hepato-gastro-enterologie de l'hôpital Gabriel Toure Bamako (Mali).

The goal of this study was to appreciate principal affections and mortality and in gastroenterology service of Gabriel Touré Hospital. It is about a survey longitudinal that has permit to analyze patients who have been care. During study, 766 patients were unregistered. Mean age of patient was 45.17 years and a sex ratio (M/F) = 1.10. The rate of reference was 13.85%. The morbidity was dominated by HIV infection (29.90%) followed by Hepato-cellular Carcinoma (7.83%) and cirrhosis (4.05%). Mortality (18.41%) was dominated by the VIH infection, HCC and Cirrhosis. The precocious recourse to cares, the improvement of work conditions, the sensitization, the infectious illness prevention is factors that will permit a reduction of morbidity and hospital mortality.

[Epidemiologic aspects of human immunodeficiency virus and hepatitis virus infections]. / Aspects epidemiologiques de la co-infection par le virus de l'immunodeficience humaine et les virus des hepatites.

In order to determinate the prevalence of hepatitis B virus and hepatitis C virus among patients infected by the HIV, We realized a transverse survey case--control in hepato-gastro-enterological ward and serology unity of National Institute of Research in Public health (INRSP). Our sample was constituted with 100 patients HIV positive compared to 100 controls HIV negative. The viral markers research has been made by methods immuno-enzymatiqueses of ELISA 3rd generation. Tests permitted to get the following results: Hepatitis B surface antigen (HBs Ag) was positive among 21% with patients HIV positive versus 23% among control (p = 0,732); Antibody to hepatitis C virus (anti-HCV ab) was present among 23% with patients HIV positive versus 0% among control (p <0,05). Female was predominant among co-infections patient, but without statistic link (p = 0,9 and p = 0,45); The co-infection HBV- HCV was significatively linked to age beyond 40 years (p = 0,0005). Co-infections with HIV infection and hepatitis virus are not rare and deserve to be investigated.

[ORL manifestations observed in AIDS. Apropos of 65 cases]. / Manifestations orl observées au cours du SIDA. A propos de 65 observations.

We realized a clinical study in 65 patients with acquired immunodeficiency syndrome, aged from 3 to 62 years old (mean, 34 years) (34 males and 31 females) interned or showed in consultations at the hospital Gabriel Touré in Bamako, Mali (departments of ENT diseases and of internal medicine), in order to analyse and to state precisely different otorhinolaryngologic manifestations in AIDS. Oropharyngeal candidiasis was the most prevalent otorhinolaryngologic manifestation (57 %). Other less common lesions were suppurative otitis media (29 %), atrophic pharyngitis (18,5 %), sinusitis (11 %), Kaposi's sarcoma (5 %) localized above all on the palate: they are however a frequent sign of infection by HIV. The manifestations merit a particular attention by otorhinolaryngologist because, although they have few influence on the general evolution of the disease, they appear as additional manifestations of infectious risks in AIDS patients.

Etude epidemiologique des affections oeso-gastro-duodenales au Mali au moyen de la fibroscopie digestive haute

L'objectif principal a ete d'evaluer au moyen de la fibroscopie digestive haute la frequence des affections oeso-gastro-duodenales au Mali. Sur 2864 examens pratiques; 1963 (68;54 pour cent) ont permis la decouverte de 2386 lesions (associations frequentes de differentes lesions). L'estomac a ete le plus frequemment touche (54;27 pour cent). Les gastrites ont domine la pathologie (46;19 pour cent). L'homme jeune de 21 a 40 ans a ete le plus affecte. Le symptome le plus frequent a ete l'epigastralgie. Il n'a ete constate aucune particularite quant a l'ncidence des anomalies constatees; selon la profession; la residence et l'ethnie

Impaired antibody levels to tetanus toxoid and pneumococcal polysaccharides in acute leukemias.

Antibody levels to the protein antigen tetanus toxoid (TTx) and the carbohydrate antigens pneumococcal capsular polysaccharides (PCP) were studied by enzyme immunoassay in 14 patients with acute lymphocytic leukemia (ALL) and 32 patients with acute non lymphocytic leukemia (ANLL) before and three weeks after initiation of chemotherapy. The antibody levels to TTx were significantly lower in ALL patients than in controls. This was associated with elevated levels of sCD8 (soluble CD8) in the serum of 12 out of the 14 ALL patients. Patients with ANLL had normal antibody levels before chemotherapy. After chemotherapy ANLL patients with septic complications had a reduced increase of antibody titers to TTx than patients without sepsis. The average antibody titers to PCP decreased in patients with sepsis, while they increased slightly in patients without sepsis. We conclude that in contrast to ANLL patients ALL patients have preexisting decreased antibody levels to thymus dependent protein antigens, while antibody levels to thymus independent carbohydrate antigens are normal in both types of leukemias.

The clinical relevance of IgG subclasses in acute leukemias: low serum IgG as a risk factor for early death due to infection in acute myelogenous leukemia.

In order to investigate the clinical significance of IgG subclass levels in adult patients treated for acute lymphocytic (ALL) or myelogenous leukemias (AML), patients were tested before and in regular intervals during and after chemotherapy. Ten patients treated for acute lymphocytic leukemia had normal total IgG and IgG subclass levels that decreased under chemotherapy. This decrease was not associated with septic complications. In contrast, total IgG and subclass levels increased in most patients with acute myelogenous leukemia during chemotherapy and bone marrow aplasia. Those patients with newly diagnosed AML and low total serum IgG before treatment with intensive remission induction chemotherapy had, however, an increased risk of early death due to septic complications.

European experience with ifosfamide in lymphomas.

In malignant lymphomas, ifosfamide-containing regimens were at first used mainly in second-line therapy and response-adapted protocols. Currently, in combination with other drugs, ifosfamide is being used in several phase-III trials. As salvage therapy in non-Hodgkin's lymphoma (NHL), IMV-Bleo (ifosfamide, methotrexate, etoposide, bleomycin) produced a complete remission (CR) rate of 41% and seemed to be particularly effective in patients with suboptimal response to first-line treatment. IBEP (ifosfamide, bleomycin, etoposide, procarbazine), in combination with procarbazine and bleomycin was an effective non-cross-resistant alternative in CHOP (cyclophosphamide, hydroxydauomycin/doxorubicin, vincristine, prednisone)-refractory NHL. In a trial of response-oriented therapy in high-grade malignant lymphoma patients, the investigators concluded that consolidation therapy was necessary even in patients with rapid response to CHOP. Patients with NHL resistant to or relapsing from conventional chemotherapy or with MOPP-ABVD (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, decarbazine)-resistant Hodgkin's disease (HD) were treated with BMV-VIP [bleomycin, plus high-dose methylprednisolone plus ifosfamide, etoposide, plus methylprednisolone]. In high-grade malignant NHL, patients received three cycles of COP-BLAM (cyclophosphamide, vincristine, procarbazine, prednisone, bleomycin, doxorubicin). Those who achieved CR received two more cycles of COP-BLAM and IMV (ifosfamide, methotrexate, etoposide) as consolidation therapy. Patients in partial remission (PR) or with less of a response to COP-BLAM were switched to IMV. After reaching CR, patients received two additional cycles as consolidation therapy. After the second restaging, patients were randomized to observation v additional radiotherapy. Of 191 patients, 148 have passed first restaging with 51% in CR; 85 went through the second restaging with 61% in CR. Of 32 patients who only reached PR after the first restaging, 15 (47%) achieved CR with IMV. For primary treatment of HD, the German Hodgkin Study Group added a third non-cross-resistant regimen, IMEP (ifosfamide, methotrexate, etoposide, prednisone), to supplement COPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABV in the primary treatment of HD. In a pilot study, 87% of 63 evaluable patients reached CR. The current phase-III protocol is comparing COPP/ABVD with fast alternating cycles of COPP/ABV/IMEP.