RESUMO
STUDY QUESTION: What is the long-term reproductive health outcome of patients who have undergone testicular sampling for fertility preservation (FP) before and during the pubertal transition period? SUMMARY ANSWER: In long-term follow-up after testicular sampling for FP, hormonal data showed that 33% of patients had primary seminiferous tubule insufficiency (high FSH) while semen analyses showed 52% of patients having a severe reduction in total sperm counts or complete absence of ejaculated sperm. WHAT IS KNOWN ALREADY: During childhood and adolescence, both treatments for cancer and benign haematological diseases that require a bone marrow transplantation, can be detrimental to spermatogenesis by depleting the spermatogonial stem cell population. A testicular biopsy prior to chemotherapy or radiotherapy, even though still an experimental procedure, is now recommended for FP by European and USA oncofertility societies if performed within an institutional research setting. While short-term follow-up studies showed little to no post-operative complications and a normal testicular development after 1 year, data regarding the long-term follow-up of boys who have undergone this procedure are still lacking. STUDY DESIGN, SIZE, DURATION: This is a longitudinal retrospective cohort study that reports on the long-term follow-up of pre- and peri-pubertal boys who have undergone a testicular biopsy for FP between May 2005 and May 2020. All the patients included in this study were referred to our programme by haematologists-oncologists who are part of a regional multi-centric collaborative care pathway. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 151 boys referred to our FP programme, 139 parents/legal guardians accepted that their child undergo a testicular biopsy. Patient characteristics (i.e. age at biopsy, urogenital history, pubertal status at diagnosis), indications (disease type and dosage of gonadotoxic treatments), operative and post-operative data (biopsy volume, surgical complications), anatomopathological analyses (presence/absence of spermatogonia, Johnsen score) and reproductive data (semen analyses, FSH, LH, testosterone levels) were collected from the institutions' FP database and medical records or from the 'Brussels Health Network'. Cumulative alkylating agent treatment was quantified using the cyclophosphamide equivalent dose (CED). Patients who were 14 years or older at the time of the follow-up and in whom the testicular tissue was shown to contain spermatogonia were included in the reproductive outcome analysis. Comparison of the sperm count findings (absence/presence of spermatozoa) and FSH levels (high (≥10 IU/l)/normal) between patients who were either pre- (Tanner 1) or peri-pubertal (Tanner >1) at the time of the biopsy was done using the Mann-Whitney U or Fisher's tests. A multiple logistic regression was used to study the relationship between the hormone reproductive outcome (high versus normal FSH), as a proxy marker for fertility, and both the pubertal status (Tanner 1 versus Tanner >1) and Johnsen score at the time of the biopsy, while adjusting for CED. MAIN RESULTS AND THE ROLE OF CHANCE: A testicular biopsy was performed in 139 patients either before (129/139) or after (10/139) the start of a gonadotoxic treatment. Post-operative complications occurred in 2.1% (3/139). At the time of the procedure, 88% (122/139) of patients were pre-pubertal and 12% (17/139) were peri-pubertal. The presence of spermatogonia was documented in 92% (128/139) of cases. Follow-up data were available for 114 patients after excluding 23 deceased and two patients lost to follow-up. A paediatric endocrinologist's follow-up including clinical examination and data on reproductive hormones was available for 57 patients (age ≥14) and 19 (33%) of these were found to have high FSH levels (20 ± 8.8 IU/l). There were 37 patients who had returned to the reproductive specialist's consultation for post-treatment fertility counselling and results on semen analysis were available in 27 of these cases; 14/27 (52%) had severely impaired semen parameters including 8 who were azoospermic. Among patients who received an alkylating agent-based treatment (n = 42), a peri-pubertal status (Tanner >1) at the time of diagnosis/biopsy was found to be associated with a higher risk of having primary testicular failure (defined by an FSH ≥ 10 IU/l) after treatment completion with an OR of 6.4 (95% CI 1.22-33.9; P = 0.03). Of all the patients, 2.6% had already fulfilled their wish to build a family or were actively seeking parenthood. LIMITATIONS, REASONS FOR CAUTION: Although this is the largest cohort with follow-up data providing proxy markers of the reproductive potential of boys in whom a testicular biopsy for FP was performed before puberty or during the pubertal transition period, the amount of data provided is limited, and originating from a single programme. Further data collection to confirm the observations in other settings is therefore awaited. WIDER IMPLICATIONS OF THE FINDINGS: Testicular sampling for FP should be offered to boys at risk of losing their fertility (and is recommended for those at high risk) as part of ethically approved research programmes. Long-term follow-up data on increasing numbers of boys who have undergone an FP procedure will help improve patient care in the future as patient-specific factors (e.g. urogenital history, age at gonadotoxic therapy) appear to influence their reproductive potential after gonadotoxic therapies. STUDY FUNDING/COMPETING INTEREST(S): FNRS-Télévie, the Salus Sanguinis Foundation and the Belgian Foundation against Cancer supported the studies required to launch the FP programme. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Preservação da Fertilidade , Adolescente , Biópsia , Criança , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , TestículoRESUMO
Multicenter studies are widely used to meet accrual targets in clinical trials. Clinical data monitoring is required to ensure the quality and validity of the data gathered across centers. One approach to this end is central statistical monitoring, which aims at detecting atypical patterns in the data by means of statistical methods. In this context, we consider the simple case of a continuous variable, and we propose a detection procedure based on a linear mixed-effects model to detect location differences between each center and all other centers. We describe the performance of the procedure as a function of contamination rate and signal-to-noise ratio. We investigate the effect of center size and variance structure and illustrate the use of the procedure using data from two multicenter clinical trials.
Assuntos
Viés , Modelos Lineares , Estudos Multicêntricos como Assunto/métodos , Razão Sinal-Ruído , Biometria/métodos , Simulação por Computador , Humanos , Reprodutibilidade dos TestesRESUMO
AIM: To compare current practice of cuff size selection for noninvasive blood pressure measurement in a single-centre, tertiary-level neonatal intensive care unit (visual assessment of bladder width/limb length closest to 2/3) with common recommendations for appropriate cuff selection. METHODS: Visual assessment of the appropriate cuff size ('2/3 rule') for upper arm, forearm and calf in 103 neonates (309 cuff selections) was compared with the following recommendations: (i) Method A - guidelines of the cuff manufacturer, (ii) Method B - cuff width/limb circumference ratio 0.44-0.60 and (iii) Method C - cuff width/limb length ratio closest to 0.66. RESULTS: The upper arm cuff size was correctly chosen in 84% of cases (Method A), 43% (Method B) and 56% (Method C). The forearm cuff size was correctly chosen in 94% of cases (Method A), 68% (Method B) and 54% (Method C). The calf cuff size was correctly chosen in 96% of cases (Method A), 72% (Method B) and 63% (Method C). CONCLUSION: The accuracy of selecting cuff size by visual assessment is low. Further research on accurate cuff selection for neonates, including at the forearm and calf, is warranted.
Assuntos
Terapia Intensiva Neonatal/métodos , Esfigmomanômetros , Braço/anatomia & histologia , Determinação da Pressão Arterial/instrumentação , Determinação da Pressão Arterial/normas , Humanos , Recém-Nascido , Terapia Intensiva Neonatal/normas , Guias de Prática Clínica como Assunto , Esfigmomanômetros/normasRESUMO
We report conversion efficiencies of experimental single and dual light guide luminescent solar concentrators. We have built several 5 cm × 5 cm and 10× cm × 10 cm luminescent solar concentrator (LSC) demonstrators consisting of c-Si photovoltaic cells attached to luminescent light guides of Lumogen F Red 305 dye and perylene perinone dye. The highest overall efficiency obtained was 4.2% on a 5 cm × 5 cm stacked dual light guide using both luminescent materials. To our knowledge, this is the highest reported experimentally determined efficiency for c-Si photovoltaic-based LSCs. Furthermore, we also produced a 5 cm × 5 cm LSC specimen based on an inorganic phosphor layer with an overall efficiency of 2.5%.
RESUMO
AIM: This study aims to determine which anthropometric (body mass index (BMI), waist-hip-ratio (WHR) and waist-to-height ratio (WHtR)) and radiological (visceral fat area (VFA) measured by CT scan) measurements of adiposity correlated better with postoperative outcome of colorectal cancer (CRC) surgery. We also assessed which of these measurements best predicted overall survival (OS) and disease-free survival (DFS). METHODS: Data from 90 consecutive Caucasian CRC patients who underwent surgery for colorectal cancer between 2010 and 2011 with a median follow-up of 53.25 months were analysed. The correlations of different adiposity measurements and postoperative outcomes were determined using logistic regression models and multivariate analyses. RESULTS: Higher WHtR (p = 0.007) and VFA (p = 0.01) significantly increased the risk of overall morbidity, especially of Clavien-Dindo III or IV. The WHtR correlated best with VFA (p <0.0001), which is considered the gold standard for measuring visceral fat, whereas BMI (p = 0.15) was not a good predictor of postoperative morbidity. Multivariate analyses showed consistently significant results for postoperative complications for VFA in combination with all of the other variables analysed and for WHtR, confirming that VFA and WHtR were reliable independent prognostic factors of morbidity. VFA had a significant effect on OS (p = 0.012) but did not correlate with DFS (p = 0.51). CONCLUSIONS: Both VFA and WHtR independently provided predictive data for potential postoperative complications after CRC surgery. In case CT scan was used for diagnostic purposes, VFA should be used in routine clinical practice.
Assuntos
Gordura Abdominal/diagnóstico por imagem , Tecido Adiposo/diagnóstico por imagem , Cirurgia Colorretal/mortalidade , Mortalidade Hospitalar , Complicações Pós-Operatórias/mortalidade , Tomografia Computadorizada por Raios X/métodos , Tecido Adiposo/anatomia & histologia , Índice de Massa Corporal , Superfície Corporal , Humanos , Complicações Intraoperatórias/mortalidade , Masculino , Morbidade , Obesidade , Fatores de Risco , Razão Cintura-Estatura , Relação Cintura-QuadrilRESUMO
BACKGROUND: It is controversial whether pediatric liver transplantation (OLT) should only be performed in a high-volume pediatric or in mixed adult/pediatric centers. We reviewed pediatric OLT results in an originally adult OLT center. METHODS/RESULTS: Our adult OLT program was initiated in 1989, currently transplanting approximately 55 livers/year. A pediatric OLT program was launched in 1999. Pre- and posttransplant follow-up is multidisciplinary. In the study period, 26 OLT were performed in 25 patients (6% of all OLT; n = 430). The mean age was 8 years (range: 1 month to 18 years). Mean weight was 22 kg (4 to 80 kg). The indications were: acute liver failure in one (4%); chronic liver failure in 25 (96%)-10 metabolic, six biliary atresia, five polycystic/liver fibrosis, four other, and one retransplant. Nine (35%) received partial graft; 5 (19%) multivisceral grafts (liver-kidney, liver-bowel) and 12 (46%), conventional OLT. In all small-weight children, microsurgery was used. Immunosuppression included calcineurin inhibitors (cyclosporine/tacrolimus), azathioprine/mycophenolate mofetil, low-dose steroid, and anti-interleukin-2 receptor in 14. Early hepatic artery thrombosis (HAT), portal vein thrombosis, and primary nonfunction were not encountered. One retransplantation (4%) was done at 4 years posttransplantation for late HAT. Three biliary complications (11%) were encountered at 2 weeks, 4 months, and 2 years. Percentage of early acute and chronic rejections were 7.7% and 0%. Three deaths occurred due to mycotic aneurysm at 2 weeks; Cytomegalovirus at 4 months; pulmonary infection at 2 years. Twenty-two of 25 patients (88%) are well at last follow-up (up to 8 years). CONCLUSION: Despite representing a small percentage of overall OLT activity pediatric OLT were performed with excellent results in a center with sufficient OLT volume and ad hoc surgical, pediatric, and intensive care team expertise.
Assuntos
Transplante de Fígado/estatística & dados numéricos , Complicações Pós-Operatórias/classificação , Adulto , Criança , Doenças da Vesícula Biliar/epidemiologia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/patologia , Artéria Hepática , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Análise de Sobrevida , Sobreviventes , Trombose/epidemiologia , Doenças Vasculares/epidemiologia , Listas de EsperaRESUMO
Until 1998, intestinal transplantation (SBT) had not been performed in our region of Flanders, Belgium. Potential SBT activity was not known and selection criteria had not been validated. A multidisciplinary SBT program was launched in 1998. We analyzed requests for SBT and outcomes in these patients whether with or without SBT. Listing for SBT was only considered for patients with irreversible short bowel syndrome who had developed life-threatening complications of total parenteral nutrition, but whose general condition was still thought compatible with surgery and immunosuppression. During the study period 1998 to 2004, one third of the requests for SBT (10/31) were deemed suitable. SBT in this group was lifesaving (100% survival) when performed in time. Mortality in this group without SBT was high (67%). Two thirds of the patients (21/31) did not fulfill the SBT inclusion criteria, either because they were "too moribund" to tolerate transplantation or because they were "too well". This preliminary study emphasized the importance of (1) early referral of potential SBT candidates, (2) adherence to strict criteria for listing patients for SBT, and (3) referral of intestinal donors to procurement organizations.
Assuntos
Intestino Delgado/transplante , Adulto , Criança , Europa (Continente) , Humanos , Nutrição Parenteral Total , Seleção de Pacientes , Transplante Homólogo/fisiologia , Resultado do TratamentoRESUMO
Mutations in an N-terminal 70-amino acid domain of bacteriophage Mu's repressor cause temperature-sensitive DNA-binding activity. Surprisingly, amber mutations can conditionally correct the heat-sensitive defect in three mutant forms of the repressor gene, cts25 (D43-G), cts62 (R47-Q) and cts71 (M28-I), and in the appropriate bacterial host produce a heat-stable Sts phenotype (for survival of temperature shifts). Sts repressor mutants are heat sensitive when in supE or supF hosts and heat resistant when in Sup degrees hosts. Mutants with an Sts phenotype have amber mutations at one of three codons, Q179, Q187, or Q190. The Sts phenotype relates to the repressor size: in Sup degrees hosts sts repressors are shorter by seven, 10, or 18 amino acids compared to repressors in supE or supF hosts. The truncated form of the sts62-1 repressor, which lacks 18 residues (Q179-V196), binds Mu operator DNA more stably at 42 degrees in vitro compared to its full-length counterpart (cts62 repressor). In addition to influencing temperature sensitivity, the C-terminus appears to control the susceptibility to in vivo Clp proteolysis by influencing the multimeric structure of repressor.
Assuntos
Adenosina Trifosfatases , Bacteriófago mu/genética , Regulação Viral da Expressão Gênica , Proteínas Repressoras/genética , Proteínas Virais/genética , Sequência de Aminoácidos , Bacteriófago mu/química , Bacteriófago mu/metabolismo , Sequência de Bases , DNA Viral , Endopeptidase Clp , Deleção de Genes , Dados de Sequência Molecular , Proteínas Repressoras/metabolismo , Serina Endopeptidases/metabolismo , Sensação Térmica , Proteínas Virais/metabolismo , Proteínas Virais Reguladoras e AcessóriasRESUMO
In bacteria lysogenic for bacteriophage Mu, the phage repressor binds to a tripartite operator region, O1,O2,O3, to repress the lytic promoter pE, located in O2, and negatively autoregulate its own synthesis at the pCM promoter located in O3. We isolated and characterized operator mutations which lead to derepression of pE. Their location in the first and third repressor-consensus-binding sequences in O2 confirms the importance of these sites for repressor/operator interactions.
Assuntos
Bacteriófago mu/genética , Regiões Operadoras Genéticas/genética , Mutação Puntual/genética , Sequência de Bases , Clonagem Molecular , Sequência Consenso , DNA Viral/metabolismo , Regulação Viral da Expressão Gênica , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Repressoras/metabolismo , Deleção de SequênciaRESUMO
Among 19 cases of arthritis of the basal joint of the thumb, 12 were operated according to the technique of Swanson, and 7 by simple trapezectomy. Similar results were observed with both techniques.
Assuntos
Ossos do Carpo/cirurgia , Osteoartrite/cirurgia , Idoso , Ossos do Carpo/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Radiografia , Procedimentos Cirúrgicos Operatórios/métodosRESUMO
The presence of a cardiac assist device in a liver transplantation candidate should not be considered to be an absolute contraindication to transplantation. In this first case report of liver transplantation in a patient with an intraabdominally located left ventricular assist device, we have described the surgical aspects and discussed the timing of the liver transplantation and the removal of the left ventricular assist device.
Assuntos
Cardiomiopatia Dilatada/terapia , Coração Auxiliar , Hepatopatias/cirurgia , Transplante de Fígado , Função Ventricular Esquerda , Adolescente , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/fisiopatologia , Remoção de Dispositivo , Humanos , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Masculino , Acidemia Propiônica/complicações , Desenho de Prótese , Fatores de Tempo , Resultado do TratamentoAssuntos
Artroplastia/efeitos adversos , Fixação Interna de Fraturas/efeitos adversos , Fixação Intramedular de Fraturas/efeitos adversos , Articulação do Quadril/cirurgia , Prótese Articular/efeitos adversos , Adulto , Idoso , Pinos Ortopédicos , Placas Ósseas , Parafusos Ósseos , Feminino , Fraturas do Fêmur/cirurgia , Fixação de Fratura/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-OperatóriasRESUMO
Using internal deletions in the Mu genome, we have mapped the gene coding for Mu modification in the beta segment of Mu DNA.
Assuntos
Bacteriófago mu/genética , Genes Virais , Adenosina/metabolismo , Mapeamento Cromossômico , DNA Viral/genética , FenótipoRESUMO
In vitro studies of bacteriophage Mu transposition have shown that the phage-encoded transposase and repressor bind the same sequences on the phage genome. We attempted to test that prediction in vivo and found that Mu repressor directly inhibits transposition. We also found that, in the absence of repressor, constitutive expression of Mu transposition functions pA and pB is lethal in Escherichia coli strains lysogenic for a mini-Mu and that this is the result of intensive replication of the mini-Mu. These findings have important consequences where such mini-Mus are used as genetic tools. We also tested whether in Erwinia chrysanthemi the effect of transposition functions on a resident mini-Mu was the same as in E. coli. We observed that expression of pA alone was lethal in E. chrysanthemi and that a large fraction of the survivors underwent precise excision of the mini-Mu.
Assuntos
Bacteriófago mu/genética , Genes Virais/genética , Lisogenia/genética , Nucleotidiltransferases/genética , Proteínas Repressoras/genética , Bacteriófago mu/enzimologia , Southern Blotting , Replicação do DNA/genética , DNA Viral/genética , Proteínas de Ligação a DNA/genética , Dickeya chrysanthemi/genética , Escherichia coli/genética , Expressão Gênica/fisiologia , Plasmídeos/genética , Transcrição Gênica/genética , Transposases , Proteínas Virais/genética , Replicação ViralRESUMO
A cartilaginous loose body of the radiocarpal joint was removed arthroscopically in a 45-year-old woman who complained of locking and snapping of her wrist. The diagnosis was made at arthroscopy and immediate relief was obtained.
Assuntos
Corpos Livres Articulares/diagnóstico por imagem , Articulação do Punho/diagnóstico por imagem , Artroscopia , Diagnóstico Diferencial , Feminino , Humanos , Corpos Livres Articulares/cirurgia , Pessoa de Meia-Idade , Radiografia , Articulação do Punho/cirurgiaRESUMO
The importance of proteases in gene regulation is well documented in both prokaryotic and eukaryotic systems. Here we describe the first example of genetic regulation controlled by the Escherichia coli Clp ATP-dependent serine protease. Virulent mutants of bacteriophage Mu, which carry a particular mutation in their repressor gene (vir mutation), successfully infect Mu lysogens and induce the resident Mu prophage. We show that the mutated repressors have an abnormally short half-life due to an increased susceptibility to Clp-dependent degradation. This susceptibility is communicated to the wild type repressor present in the same cell, which provides the Muvir phages with their trans-dominant phenotype. To our knowledge this is the first case where the instability of a mutant protein is shown to trigger the degradation of its wild type parent.
Assuntos
Bacteriófago mu/patogenicidade , Escherichia coli/enzimologia , Proteínas de Choque Térmico , Serina Endopeptidases/metabolismo , Proteases Dependentes de ATP , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , DNA Fúngico , Regulação Enzimológica da Expressão Gênica , Hidrólise , Dados de Sequência Molecular , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Proteínas Virais Reguladoras e Acessórias , Virulência/genéticaRESUMO
Growth of bacteriophage Mu was severely inhibited at elevated temperature in mutants defective in the heat shock genes dnaK, groEL, and groES and in the rpoH (htpR) regulatory mutant, but not in mutants defective in the heat shock genes dnaJ or grpE; growth of a mutant of Mu deficient in functions encoded in the accessory region of the Mu genome was inhibited in the latter two host mutants. Phage production in the dnaJ mutant was restored by growth in low-salt medium. The stage in Mu development primarily affected in all except the groE mutants was phage late transcription. In contrast, the groE mutants did not support growth of Mu at any temperature; neither Mu DNA replication nor transcription was inhibited in these strains, suggesting that groE is required for phage morphogenesis as observed with several other coliphages.