ABSTRACT
Interstitial 14q32 deletions involving IGH gene are infrequent events in chronic lymphocytic leukemia (CLL), affecting less than 5% of patients. To date, little is known about their clinical impact and molecular underpinnings, and its mutational landscape is currently unknown. In this work, a total of 871 CLLs were tested for the IGH break-apart probe, and 54 (6.2%) had a 300 kb deletion of 3'IGH (del-3'IGH CLLs), which contributed to a shorter time to first treatment (TFT). The mutational analysis by next-generation sequencing of 317 untreated CLLs (54 del-3'IGH and 263 as the control group) showed high mutational frequencies of NOTCH1 (30%), ATM (20%), genes involved in the RAS signaling pathway (BRAF, KRAS, NRAS, and MAP2K1) (15%), and TRAF3 (13%) within del-3'IGH CLLs. Notably, the incidence of TRAF3 mutations was significantly higher in del-3'IGH CLLs than in the control group (p < .001). Copy number analysis also revealed that TRAF3 loss was highly enriched in CLLs with 14q deletion (p < .001), indicating a complete biallelic inactivation of this gene through deletion and mutation. Interestingly, the presence of mutations in the aforementioned genes negatively refined the prognosis of del-3'IGH CLLs in terms of overall survival (NOTCH1, ATM, and RAS signaling pathway genes) and TFT (TRAF3). Furthermore, TRAF3 biallelic inactivation constituted an independent risk factor for TFT in the entire CLL cohort. Altogether, our work demonstrates the distinct genetic landscape of del-3'IGH CLL with multiple molecular pathways affected, characterized by a TRAF3 biallelic inactivation that contributes to a marked poor outcome in this subgroup of patients.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Genes, Immunoglobulin Heavy Chain , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Mutation , Prognosis , TNF Receptor-Associated Factor 3/geneticsABSTRACT
BACKGROUND: Covid-19 pandemic has particularly affected older people living in Long-term Care settings in terms of infection and mortality. METHODS: We carried out a cross-sectional analysis within a cohort of Long-term care nursing home residents between March first and June thirty, 2020, who were ≥ 65 years old and on whom at least one PCR test was performed. Socio-demographic, comorbidities, and clinical data were recorded. Facility size and community incidence of SARS-CoV-2 were also considered. The outcomes of interest were infection (PCR positive) and death. RESULTS: A total of 8021 residents were included from 168 facilities. Mean age was 86.4 years (SD = 7.4). Women represented 74.1%. SARS-CoV-2 infection was detected in 27.7% of participants, and the overall case fatality rate was 11.3% (24.9% among those with a positive PCR test). Epidemiological factors related to risk of infection were larger facility size (pooled aOR 1.73; P < .001), higher community incidence (pooled aOR 1.67, P = .04), leading to a higher risk than the clinical factor of low level of functional dependence (aOR 1.22, P = .03). Epidemiological risk factors associated with mortality were male gender (aOR 1.75; P < .001), age (pooled aOR 1.16; P < .001), and higher community incidence (pooled aOR 1.19, P = < 0.001) whereas clinical factors were low level of functional dependence (aOR 2.42, P < .001), Complex Chronic Condition (aOR 1.29, P < .001) and dementia (aOR 1.33, P <0.001). There was evidence of clustering for facility and health area when considering the risk of infection and mortality (P < .001). CONCLUSIONS: Our results suggest a complex interplay between structural and individual factors regarding Covid-19 infection and its impact on mortality in nursing-home residents.
Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Long-Term Care , Male , Nursing Homes , Pandemics , Risk FactorsABSTRACT
Myelodysplastic syndromes (MDS) are hematological disorders at high risk of progression to secondary acute myeloid leukemia (sAML). However, the mutational dynamics and clonal evolution underlying disease progression are poorly understood at present. To elucidate the mutational dynamics of pathways and genes occurring during the evolution to sAML, next generation sequencing was performed on 84 serially paired samples of MDS patients who developed sAML (discovery cohort) and 14 paired samples from MDS patients who did not progress to sAML during follow-up (control cohort). Results were validated in an independent series of 388 MDS patients (validation cohort). We used an integrative analysis to identify how mutations, alone or in combination, contribute to leukemic transformation. The study showed that MDS progression to sAML is characterized by greater genomic instability and the presence of several types of mutational dynamics, highlighting increasing (STAG2) and newly-acquired (NRAS and FLT3) mutations. Moreover, we observed cooperation between genes involved in the cohesin and Ras pathways in 15-20% of MDS patients who evolved to sAML, as well as a high proportion of newly acquired or increasing mutations in the chromatin-modifier genes in MDS patients receiving a disease-modifying therapy before their progression to sAML.
Subject(s)
Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Neoplasms, Second Primary , Cell Cycle Proteins , Chromosomal Proteins, Non-Histone , Humans , Leukemia, Myeloid, Acute/genetics , Mutation , Myelodysplastic Syndromes/genetics , CohesinsABSTRACT
SF3B1 is a highly mutated gene in myelodysplastic syndrome (MDS) patients, related to a specific subtype and parameters of good prognosis in MDS without excess blasts. More than 40% of MDS patients carry at least two myeloid-related gene mutations but little is known about the impact of concurrent mutations on the outcome of MDS patients. In applying next-generation sequencing (NGS) with a 117 myeloid gene custom panel, we analyzed the co-occurrence of SF3B1 with other mutations to reveal their clinical, biological, and prognostic implications in very low/low- and intermediate-risk MDS patients. Mutations in addition to those of SF3B1 were present in 80.4% of patients (median of 2 additional mutations/patient, range 0-5). The most frequently mutated genes were as follows: TET2 (39.2%), DNMT3A (25.5%), SRSF2 (10.8%), CDH23 (5.9%), and ASXL1, CUX1, and KMT2D (4.9% each). The presence of at least two mutations concomitant with that of SF3B1 had an adverse impact on survival compared with those with the SF3B1 mutation and fewer than two additional mutations (median of 54 vs. 87 months, respectively: p = 0.007). The co-occurrence of SF3B1 mutations with specific genes is also linked to a dismal prognosis: SRSF2 mutations were associated with shorter overall survival (OS) than SRSF2wt (median, 27 vs. 75 months, respectively; p = 0.001), concomitant IDH2 mutations (median OS, 11 [mut] vs. 75 [wt] months; p = 0.001), BCOR mutations (median OS, 11 [mut] vs. 71 [wt] months; p = 0.036), and NUP98 and STAG2 mutations (median OS, 27 and 11 vs. 71 months, respectively; p = 0.008 and p = 0.002). Mutations in CHIP genes (TET2, DNMT3A) did not significantly affect the clinical features or outcome. Our results suggest that a more comprehensive NGS study in low-risk MDS SF3B1mut patients is essential for a better prognostic evaluation.
Subject(s)
Myelodysplastic Syndromes/genetics , Phosphoproteins/genetics , RNA Splicing Factors/genetics , Adult , Aged , Aged, 80 and over , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Methyltransferase 3A , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Dioxygenases , Female , Humans , Male , Middle Aged , Mutation , Myelodysplastic Syndromes/diagnosis , Prognosis , Proto-Oncogene Proteins/geneticsABSTRACT
Chromosome 14q32 rearrangements/translocations involving the immunoglobulin heavy chain (IGH) are rarely detected in chronic lymphocytic leukemia (CLL). The prognostic significance of the IGH translocation is controversial and its mutational profile remains unknown. Here, we present for the first time a comprehensive next-generation sequencing (NGS) analysis of 46 CLL patients with IGH rearrangement (IGHR-CLLs) and we demonstrate that IGHR-CLLs have a distinct mutational profile with recurrent mutations in NOTCH1, IGLL5, POT1, BCL2, FBXW7, ZMYM3, MGA, BRAF and HIST1H1E genes. Interestingly, BCL2 and FBXW7 mutations were significantly associated with this subgroup and almost half of BCL2, IGLL5 and HISTH1E mutations reported were previously identified in non-Hodgkin lymphomas. Notably, IGH/BCL2 rearrangements were associated with a lower mutation frequency and carried BCL2 and IGLL5 mutations, while the other IGHR-CLLs had mutations in genes related to poor prognosis (NOTCH1, SF3B1 and TP53) and shorter time to first treatment (TFT). Moreover, IGHR-CLLs patients showed a shorter TFT than CLL patients carrying 13q-, normal fluorescence in situ hybridization (FISH) and +12 CLL, being this prognosis particularly poor when NOTCH1, SF3B1, TP53, BIRC3 and BRAF were also mutated. The presence of these mutations not only was an independent risk factor within IGHR-CLLs, but also refined the prognosis of low-risk cytogenetic patients (13q-/normal FISH). Hence, our study demonstrates that IGHR-CLLs have a distinct mutational profile from the majority of CLLs and highlights the relevance of incorporating NGS and the status of IGH by FISH analysis to refine the risk-stratification CLL model.
Subject(s)
Gene Regulatory Networks , Immunoglobulin Heavy Chains/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Mutation , Translocation, Genetic , Adult , Aged , Aged, 80 and over , Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, Pair 14/genetics , Female , Genetic Predisposition to Disease , High-Throughput Nucleotide Sequencing/methods , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Prognosis , Sequence Analysis, DNAABSTRACT
Indeterminate dendritic cell tumor (IDCT) is a rare disease composed of so-called indeterminate cells, a dendritic cell subset displaying histological and some ultrastructural and immunophenotypic features of Langerhans cells, but lacking Birbeck granules. We report a case of cutaneous IDCT occurring in a patient with chronic myelomonocytic leukemia (CMML) successfully treated with UV-A phototherapy. Next-generation sequencing studies of the CMML demonstrated mutations in TET2, ASXL1, and ZRS2 genes, also detected in the IDCT, demonstrating a clonal relationship between both tumors and confirming IDCT as a specific subtype in the spectrum of CMML-related cutaneous lesions.
Subject(s)
Langerhans Cells/pathology , Leukemia, Myelomonocytic, Chronic/pathology , Skin Neoplasms/pathology , Aged, 80 and over , Humans , Leukemia, Myelomonocytic, Chronic/therapy , Male , PhototherapyABSTRACT
BACKGROUND: The purpose of our study was to analyse the usefulness of Choi criteria versus RECIST in patients with pancreatic neuroendocrine tumours (PanNETs) treated with sunitinib. METHOD: A multicentre, prospective study was conducted in 10 Spanish centres. Computed tomographies, at least every 6 months, were centrally evaluated until tumour progression. RESULTS: One hundred and seven patients were included. Median progression-free survival (PFS) by RECIST and Choi were 11.42 (95% confidence interval [CI], 9.7-15.9) and 15.8 months (95% CI, 13.9-25.7). PFS by Choi (Kendall's τ = 0.72) exhibited greater correlation with overall survival (OS) than PFS by RECIST (Kendall's τ = 0.43). RECIST incorrectly estimated prognosis in 49.6%. Partial response rate increased from 12.8% to 47.4% with Choi criteria. Twenty-four percent of patients with progressive disease according to Choi had stable disease as per RECIST, overestimating treatment effect. Choi criteria predicted PFS/OS. Changes in attenuation occurred early and accounted for 21% of the variations in tumour volume. Attenuation and tumour growth rate (TGR) were associated with improved survival. CONCLUSION: Choi criteria were able to capture sunitinib's activity in a clinically significant manner better than RECIST; their implementation in standard clinical practice shall be strongly considered in PanNET patients treated with this drug.
Subject(s)
Antineoplastic Agents/therapeutic use , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/drug therapy , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/drug therapy , Sunitinib/therapeutic use , Adult , Aged , Aged, 80 and over , Confidence Intervals , Female , Humans , Male , Middle Aged , Neuroendocrine Tumors/mortality , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Progression-Free Survival , Proportional Hazards Models , Prospective Studies , Response Evaluation Criteria in Solid Tumors , Tomography, X-Ray Computed , Tumor Burden , Young AdultABSTRACT
Diagnosis of inherited bleeding disorders (IBDs) remains challenging, especially in the case of inherited platelet disorders, due to the heterogeneity of the clinical and laboratory phenotype, the limited specificity of platelet function tests, and the large number of potential culprit genes. Unraveling the underlying molecular defect provides the definitive diagnosis of IBDs, facilitating prognosis and clinical care, which are especially important for severe clinical syndromes and those that may be associated with an increased risk of malignancy. Until recently, Sanger sequencing of candidate genes has been the only method of molecular diagnosis, but this approach is time-consuming and costly and requires phenotype-based identification of any obvious candidate gene(s). Nowadays, high-throughput sequencing (HTS) allows the simultaneous and rapid investigation of multiple genes at a manageable cost. This HTS technology that includes targeted sequencing of prespecified genes, whole-exome sequencing, or whole-genome sequencing, is revolutionizing the genetic diagnosis of human diseases. Through its extensive implementation in research and clinical practice, HTS is rapidly improving the molecular characterization of IBDs. However, despite the availability of this powerful approach, many patients still do not receive a diagnosis. As IBDs are complex and rare diseases, development of more advanced laboratory assays, improvements in bioinformatic pipelines, and the formation of multidisciplinary teams are encouraged to advance our understanding of IBDs.
Subject(s)
Blood Platelet Disorders/genetics , Hemorrhagic Disorders/genetics , High-Throughput Nucleotide Sequencing/methods , HumansABSTRACT
We report on the site-selective synthesis of PCBM-like [70]fullerene site-isomers, where the elusive ß-site-isomers are, for the first time, the major product in a (cyclo)addition chemical reaction involving [70]fullerene. The reaction involves an straightforward cyclopropanation of [70]fullerene from sulfonium salts, affording a mixture of α and ß site-isomers in good yields. Amazingly, the preference for the α- or ß-site-isomer can be efficiently controlled by means of the solvent polarity! DFT theoretical calculations (DMF and toluene) nicely predict that, although the formation of the α-adduct is, as expected, thermodynamically favored, the selectivity of the process is determined by the energy difference of the respective transition states. Furthermore, the employ of α or/and ß site-isomers, as pure materials or as a mixture of them, used as templating agent, has been evaluated in perovskite solar cells. The positive influence of the [70]fullerenes by passivating the voids/pin-holes and/or deep slits, is reflected in highly efficient and stable bulk heterojunction perovskite solar cells, whose performance (around 20 %) is slightly but consistently depending on the isomeric fullerene composition. These experimental findings pave the way to investigate a new reactivity on C70 and to explore the properties of the less-known ß-derivatives.
ABSTRACT
A full-scale biotrickling filter (BTF) treating acetone air emissions of wood-coating activities showed difficulties to achieve outlet concentrations lower than 125 mg C m-3, especially for high inlet concentrations and oscillating emissions. To solve this problem, a laboratory investigation on acetone removal was carried out simulating typical industrial conditions: discontinuous and variable inlet concentrations and intermittent spraying. The results were evaluated in terms of removal efficiency and outlet gas emission pattern. Industrial emissions and operational protocols were simulated: inlet load up to 70 g C m-3 h-1 during 2 cycles of 4 h per day and intermittent trickling of 15 min per hour. The outlet gas stream of the pollutant was affected by intermittent spraying, causing a fugitive emission of pollutant. Complete removal efficiency was obtained during non-spraying. Average removal efficiencies higher than 85% were obtained, showing the feasibility of BTF to treat acetone. The outlet gas stream showed a clear dependence on the pH of the trickling liquid, decreasing the removal at pH < 5.5. Thus, a proper control of alkalinity, with regular NaHCO3 addition, was required for successful operation. The laboratory findings were fruitfully transferred to the industry, and the removal of acetone by full-scale BTF was improved.
Subject(s)
Acetone/isolation & purification , Air Filters , Filtration , Vehicle Emissions , Air Pollutants/isolation & purification , Bioreactors , Equipment Design , Filtration/instrumentation , Filtration/methods , Laboratories , Technology Transfer , Vehicle Emissions/prevention & control , Volatile Organic Compounds/isolation & purificationABSTRACT
The synthesis and characterization of a covalent all-fullerene C60 -Lu3 N@Ih -C80 electron donor-acceptor conjugate has been realized by sequential 1,3-dipolar cycloaddition reactions of azomethine ylides on Lu3 N@Ih -C80 and C60 . To the best of our knowledge, this is the first time that two fullerenes behaving as both electron donor (Lu3 N@Ih -C80 ) and acceptor (C60 ) are forming an electroactive dumbbell. DFT calculations reveal up to 16 diastereomeric pairs, that is, 8 with syn and 8 with anti orientation, with the anti-RSSS isomer being the most stable. Spectroelectrochemical absorption and femtosecond transient absorption experiments support the notion that a C60 â - -Lu3 N@Ih -C80 â + charge-separated state is formed. Spin conversion from the charge-separated singlet state C60 â - -Lu3 N@Ih -C80 â + into the corresponding triplet state is facilitated by the heavy-atom effect stemming from the Lu3 N-cluster, which, in turn, slows down the charge recombination by one order of magnitude.
ABSTRACT
In this work, the Bingel-Hirsch addition of diethylbromomalonate to all non-equivalent bonds of Sc3N@D3h -C78 was studied using density functional theory calculations. The regioselectivities observed computationally allowed the proposal of a set of rules, the predictive aromaticity criteria (PAC), to identify the most reactive bonds of a given endohedral metallofullerene based on a simple evaluation of the cage structure. The predictions based on the PAC are fully confirmed by both the computational and experimental exploration of the Bingel-Hirsch reaction of Sc3N@D5h -C80, thus indicating that these rules are rather general and applicable to other isolated pentagon rule endohedral metallofullerenes.
ABSTRACT
In this work, we briefly report some attempts to control regioisomeric bisadditions on Sc3N@Ih-C80 and Lu3N@Ih-C80 using the tether-controlled multifunctionalization method. We then describe the use of independent (nontethered) bis-1,3-dipolar cycloaddition reactions and the characterization of 5 new bisadducts, 3 for Sc3N@C80 and 2 for Lu3N@C80, which have never been reported before. Unexpectedly and remarkably, 4 of these compounds exhibit relatively high symmetry and 2 of these bisadducts are the first examples of intrinsically chiral endohedral compounds, due to the addition pattern, not to the presence of chiral centers on the addends. Since an analysis of the statistically possible number of bisadduct isomers on an Ih-C80 cage has not been reported, we present it here.
ABSTRACT
The regioselective synthesis of easily isolable pure bismethano derivatives of C60 and C70 with high steric congestion is described using 1,3-dibenzoylpropane bis-p-toluenesulfonyl hydrazone as the addend precursor. When the addition occurs at two [6,6] ring junctions within the same hexagon, bisadducts with mirror symmetry are obtained for both C60 and C70. When the addition occurs at two [5,6] ring junctions in C60, a symmetrical adduct is formed, which readily undergoes photo-oxygenation and ring opening to yield a fullerene with a hole in the cage. In this work, we also propose a simple and general system to name all of the possible [6,6] bisadduct isomers on C70.
Subject(s)
Fullerenes/chemistry , Isomerism , Models, Molecular , Molecular StructureABSTRACT
Fullerenes are among the most studied molecules during the last three decades, and therefore, a huge number of chemical reactions have been tested on these new carbon allotropes. However, the aim of most of the reactions carried out on fullerenes has been to afford chemically modified fullerenes that are soluble in organic solvents or even water in the search for different mechanical, optical, or electronic properties. Therefore, although a lot of effort has been devoted to the chemical functionalization of these molecular allotropes of carbon, important aspects in the chemistry of fullerenes have not been properly addressed. In particular, the synthesis of chiral fullerenes at will in an efficient manner using asymmetric catalysis has not been previously addressed in fullerene science. Thus, despite the fact that the chirality of fullerenes has always been considered a fundamental issue, the lack of a general stereoselective synthetic methodology has restricted the use of enantiopure fullerene derivatives, which have usually been obtained only after highly expensive HPLC isolation on specific chiral columns or prepared from a pool of chiral starting materials. In this Account, we describe the first stereodivergent catalytic enantioselective syntheses in fullerene science, which have allowed the highly efficient synthesis of enantiomerically pure derivatives with total control of the stereochemical result using metallic catalysts and/or organocatalysts under very mild conditions. Density functional theory calculations strongly support the experimental findings for the assignment of the absolute configuration of the new stereocenters, which has also been ascertained by application of the sector rule and single-crystal X-ray diffraction. The use of the curved double bond of fullerene cages as a two-π-electron component in a variety of stereoselective cycloaddition reactions represents a challenging goal considering that, in contrast to most of the substituted olefins used in these reactions, pristine fullerene is a noncoordinating dipolarophile. The aforementioned features make the study of stereoselective 1,3-dipolar cycloadditions onto fullerenes a unique scenario to shed light onto important mechanistic aspects. On the other hand, the availability of achiral starting materials as well as the use of nonexpensive asymmetric catalysts should provide access to chiral fullerenes and their further application in a variety of different fields. In this regard, in addition to biomedical applications, chiral fullerenes are of interest in less-studied areas such as materials science, organic electronics, and nanoscience, where control of the order and morphology at the nanometer scale are critical issues for achieving better device efficiencies.
ABSTRACT
Four easily isolable regio- and stereoselective bis-adducts of C60 and C70 , as well as a new C70 -dumbbell derivative, have been synthesized by using two different bismalonate tethered moieties. The derivatives that possess relatively long-tethered moieties show highly symmetric addition patterns, as evidenced by spectroscopic measurements, whereas the derivatives possessing the shorter-tethered moiety exhibit interesting addition patterns on C60 and C70 .
ABSTRACT
Novel chiral catalytic systems based on both organic compounds and metal salts have been developed for the enantioselective [3 + 2] cycloaddition of münchnones onto fullerenes and olefins. These two different approaches proved to be efficient and complementary in the synthesis of optically active pyrrolino[3,4:1,2][60]fullerenes with high levels of enantiomeric excess and moderate to good conversions. Further functionalization of the pyrrolinofullerene carboxylic acid derivatives has been carried out by esterification and amidation reactions.
Subject(s)
Fullerenes/chemistry , Metals/chemistry , Organic Chemicals/chemistry , Oxazoles/chemistry , Catalysis , Cycloaddition Reaction , Ligands , Maleimides/chemistry , Oxazolone/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
Despite numerous studies on hydrochar use, its application in water treatment for pathogen removal remains unexplored. In this study, we evaluated the efficiency of hydrochar produced from crop residue of maize for water treatment by determining breakthrough from sand columns supplemented with hydrochar. To enhance the adsorptive capacity, raw hydrochar was activated by 1 mol L KOH at room temperature. The experiments conducted in a 10-cm sand bed with 1.5% (w/w) activated and raw hydrochar supplements, not activated by KOH, showed 93 and 72% of removal efficiencies, respectively. Activation of KOH not only enhanced the removal but also increased the strength of the attachment: 96% of the retained in the column with activated hydrochar supplements was shown to be irreversibly attached, compared with only 65% for the raw hydrochar. Scanning electron microscopy/energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and zeta-potential analyses suggested that these improvements were mainly due to the development of a well-formed porous surface structure and less negative surface charges on the activated hydrochar.
ABSTRACT
OBJECTIVES: Urethral stenosis is a complex pathology that severely affects the quality of life of patients who suffer it. There are multiple therapeutic options, the main objective of which is to eliminate obstruction and improve symptoms, and consequently maintain or improve the quality of life of the patient. The objective of this article is to perform a systematic review of the literature with the aim to evaluate the results regarding the sexual sphere after urethral surgery. METHODS: We performed a bibliographic search in PubMed, identifying studies that analyzed the results in sexual function after various types of urethroplasties. Preference have been given to those articles evaluating sexual function both preoperative and postoperative, to determine the degree of involvement conditioned by surgery. Fourteen articles have been selected, including those making reference to sexual function (sexual desire, erectile and ejaculatory function). RESULTS: A total of 14 studies were selected to perform the analysis; they were divided into two groups depending of the perspective they have to evaluate results: Use of validated tests for data collection before and after surgery and a second group analyzing more qualitative features of the stenosis making the evaluation of results this way. Site of stenosis is not uniformly distributed in these articles, with predominance of those performing anterior urethra surgery. They have a comprehensive analysis of the various features that may affect directly or indirectly the result of the operation both in the short and long term. CONCLUSIONS: Most articles conclude that specific standardized tools are necessary for this type of pathology, with the aim of obtain results that are more adjusted to urethral surgery. Patient perception of the results of urethroplasty is a parameter that has gained great importance lately. Globally the results of postoperative sexual function are very satisfactory, mainly in young patients. It is important to globally analyze the results and surgical techniques currently in use with the aim to minimize deleterious effects on sexual function; moreover taking into account that the objective of surgery is to try to improve the patient's quality of life.
Subject(s)
Plastic Surgery Procedures/methods , Sexual Dysfunction, Physiological/etiology , Urethral Stricture/surgery , Urologic Surgical Procedures, Male/methods , Adult , Age Factors , Aged , Comorbidity , Ejaculation , Erectile Dysfunction/etiology , Erectile Dysfunction/therapy , Humans , Intraoperative Complications/etiology , Intraoperative Complications/therapy , Libido , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/therapy , Quality of Life , Plastic Surgery Procedures/adverse effects , Sexual Dysfunction, Physiological/therapy , Surgical Flaps , Treatment Outcome , Urologic Surgical Procedures, Male/adverse effectsABSTRACT
Testosterone Deficiency Syndrome is associated with age. Recent studies advocate for the safety of hormonal treatment with testosterone in patients with history of Prostate Cancer (PC) ,once disease-free survival is confirmed. A total of five publications describe 110 patients treated with testosterone replacement therapy, having a history of PC, who had undergone radical prostatectomy (RP). Only one patient had biochemical recurrence during replacement therapy. Testosterone replacement therapy must be indicated in selected patients with history of low risk localized prostate cancer treated satisfactorily who are symptomatic and have good oncological control. The testosterone levels to achieve should be the minimum effective to obtain a symptomatic response. Adequate information on the benefits and potential risks must be understood and accepted by the patient.