Long-term use of prescription opioids for non-cancer pain and mortality: a population-based, propensity-weighted cohort study.

OBJECTIVE: The objective of this study was to identify factors associated with long-term opioid use and to assess the association between long-term use and death. STUDY DESIGN: Retrospective cohort study combining several population-wide databases and covering a population of five million inhabitants, including all adults who were initiated on opioid treatment from 2014 to 2018 for non-cancer pain. METHODS: We used logistic regression models to identify factors associated with chronic opioid use and carried out survival analyses using multivariable Cox regression modelling for all-cause mortality during follow-up using inverse probability of treatment weighting (IPTW) and propensity scores based on the probability of using opioids chronically. RESULTS: Among 760,006 patients, 82,423 (10.85%) used opioids for 90 days or more after initiation. Initial therapy characteristics associated with higher risk for long-term use were initiating with long- and short-acting opioids (when compared to tramadol, odds ratio [OR]: 2.63, 95% confidence interval [CI]: 2.57, 2.69 and OR: 1.60, 95%CI: 1.46, 1.76, respectively), using higher daily doses (when compared to 50 morphine milligramme equivalent [MME] or less, prescribing 50 to 89 daily MME, OR: 1.76, 95%CI: 1.65, 1.87; 90 to 119 daily MME, OR: 2.44, 95%CI: 1.99, 3.01; and more than 120 daily MME, OR: 1.77, 95%CI: 1.64, 1.91), and overlapping with gabapentinoids (OR: 2.26, 95%CI: 2.20, 2.32), benzodiazepines (OR: 1.32, 95%CI: 1.30, 1.35), and antipsychotics (OR: 1.21, 95%CI: 1.16, 1.26). After IPTW, chronic opioid use was associated with higher risk of all-cause mortality when compared to short-term use (Hazard Ratio (HR): 1.37, 95%CI: 1.32, 1.42). Sensitivity analyses provided similar results. CONCLUSION: These findings may help healthcare managers to identify and address patients at higher risk of long-term use and riskier prescription patterns.

Dyslipidemia alters sperm maturation and capacitation in LXR-null mice.

Lipid metabolism disorders (dyslipidemia) are causes of male infertility, but little is known about their impact on male gametes when considering post-testicular maturation events, given that studies concentrate most often on endocrine dysfunctions and testicular consequences. In this study, three-month-old wild-type (wt) and Liver-X-Receptors knock out (Lxrα;ß-/- ) males were fed four weeks with a control or a lipid-enriched diet containing 1.25% cholesterol (high cholesterol diet (HCD)). The HCD triggered a dyslipidemia leading to sperm post-testicular alterations and infertility. Sperm lipids were analyzed by LC-MS and those from Lxrα;ß-/- males fed the HCD showed higher chol/PL and PC/PE ratios compared to wt-HCD (P < 0.05) and lower oxysterol contents compared to wt (P < 0.05) or Lxrα;ß-/- (P < 0.05). These modifications impaired membrane-associated events triggering the tyrosine phosphorylation normally occurring during the capacitation process, as shown by phosphotyrosine Western blots. Using flow cytometry, we showed that a smaller subpopulation of spermatozoa from Lxrα;ß-/- -HCD males could raise their membrane fluidity during capacitation (P < 0.05 vs wt or wt-HCD) as well as their intracellular calcium concentration (P < 0.05 vs Lxrα;ß-/- and P < 0.001 vs wt). The accumulation of the major sperm calcium efflux pump (PMCA4) was decreased in Lxrα;ß-/- males fed the HCD (P < 0.05 vs Lxrα;ß-/- and P < 0.001 vs wt). This study is the first showing an impact of dyslipidemia on post-testicular sperm maturation with consequences on the capacitation signaling cascade. It may lead to the identification of fertility prognostic markers in this pathophysiological situation, which could help clinicians to better understand male infertilities which are thus far classified as idiopathic.

Cellular changes in the hamster testicular interstitium with ageing and after exposure to short photoperiod.

The aim of this study was to evaluate the cellular changes that occur in the hamster testicular interstitium in two very different physiological situations involving testicular involution: ageing and exposure to a short photoperiod. The animals were divided into an 'age group' with three subgroups - young, adult and old animals - and a 'regressed group' with animals subjected to a short photoperiod. The testicular interstitium was characterised by light and electron microscopy. Interstitial cells were studied histochemically with regard to their proliferation, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end labelling (TUNEL+) and testosterone synthetic activity. We identified two types of Leydig cell: Type A cells showed a normal morphology, while Type B cells appeared necrotic. With ageing, pericyte proliferation decreased but there was no variation in the index of TUNEL-positive Leydig cells. In the regressed group, pericyte proliferation was greater and TUNEL-positive cells were not observed in the interstitium. The testicular interstitium suffered few ultrastructural changes during ageing and necrotic Leydig cells were observed. In contrast, an ultrastructural involution of Leydig cells with no necrosis was observed in the regressed group. In conclusion, the testicular interstitium of Mesocricetus auratus showed different cellular changes in the two groups (age and regressed), probably due to the irreversible nature of ageing and the reversible character of changes induced by short photoperiod.

Telocyte Behaviour During Inflammation, Repair and Tumour Stroma Formation.

In this chapter, we outline the role of human CD34+ stromal cells/telocytes (CD34+ SC/TCs) as progenitor cells during repair. The in vivo activation phenomena of CD34+ SC/TCs in this process include increased size; separation from the neighbouring structures (mainly of the vascular walls); association with inflammatory cells, predominantly macrophages; development of the organelles of synthesis (rough endoplasmic reticulum and Golgi apparatus); cell proliferation with presence of mitosis and high proliferative index (transit-amplifying cells); and fibroblastic and myofibroblastic differentiation. A procedure to study these tissue-resident cells, comparison of their behaviour in vivo and in vitro and different behaviour depending on location, time, type of injury (including tumour stroma) and greater or lesser proximity to the injury are also considered.

Mediterranean diet and childhood asthma.

BACKGROUND: The incidence of bronchial hyperreactivity has increased to one-third of the population in developed countries, which requires the adoption of preventive and therapeutic measures. The objective of the present study was to assess the effects of a traditional Mediterranean diet on patients diagnosed with childhood asthma and determine if there is a beneficial effect from this dietary intervention. METHODS: Prospective before-after comparison study of 50 girls and 54 boys aged 1-5 years, who were enrolled in the 1-year programme "Learning to Eat from the Mediterranean", designed to promote the adoption of a traditional Mediterranean diet. We studied the clinical and therapeutic variables and anthropometric measurements. RESULTS: All studied symptomatic indicators (number and intensity of asthmatic attack, infections and hospital admissions) showed a positive and statistically significant evolution of bronchial hyperreactivity from the first weeks of the intervention onwards. Throughout the treatment, 32.2% of patients remained free of crisis, 35.3% of the patients only had one attack throughout the year and 24.9% had two episodes, compared to 4.73 episodes on average in the previous year. The use of inhaled corticosteroids markedly decreased from 3.92 ± 1.61 to 1.11 ± 1.09 times per patient per year (P<0.001) and that of inhaled bronchodilators decreased from 4.14 ± 1.61 to 1.12 ± 1.40 (P<0.001). As a result, the families involved in the programme reported a high level of satisfaction. CONCLUSIONS: The adoption of a traditional Mediterranean diet could contribute significantly to the improvement of patients diagnosed with childhood asthma.

Changes in Testicular Interstitial Connective Tissue of Hamsters (Mesocricetus auratus) During Ageing and After Exposure to Short Photoperiod.

The testicular interstitium of Syrian hamster (Mesocricetus auratus) was studied during ageing and in testicular regression after exposure to a short photoperiod, in relation to the interstitial cells and their connective tissue. This tissue was assessed histochemically using Masson's trichrome technique and the expression of Heat Shock Protein 47 (HSP-47) and collagen IV (α5) was assessed in Leydig cells. Finally, an ultrastructural analysis of some cells of the testicular interstitium was made. Leydig cells were positive for HSP-47 and collagen IV (α5). Ageing did not change the parameters studied while the short photoperiod altered the synthetic activity of Leydig cells. The positivity index of these cells for HSP-47 was significantly higher in the regressed testis, but was lower for collagen IV (α5). During ageing no change were observed. Ultrastructural Leydig cells showed a discontinuous basal lamina that did not change during ageing. The basal lamina was not identified in Leydig cells regressed by exposure to a short photoperiod. In conclusion; the intertubular connective tissue suffers little change with age. By contrast, in the testis regressed after exposure to a short photoperiod the studied parameters related to the intertubular connective tissue were altered. These changes are probably related with the low synthetic activity of regressed Leydig cell.

Lectin histochemistry as a tool to identify apoptotic cells in the seminiferous epithelium of Syrian hamster (Mesocricetus auratus) subjected to short photoperiod.

Lectins have been widely used to study the pattern of cellular glycoconjugates in numerous species. In the process of cellular apoptosis, it has been observed that changes occur in the membrane sugar sequences of these apoptotic cells. The aim of our work was to identify which lectins, out of an extensive battery of the same (PNA, SBA, HPA, LTA, Con-A, UEA-I, WGA, DBA, MAA, GNA, AAA, SNA), show affinity for germinal cells in apoptosis, at what stage of cell death they do so and in which germinal cell types they can be detected. For this, we studied testis sections during testicular regression in Syrian hamster (Mesocricetus auratus) subjected to short photoperiod. Several lectins showed an affinity for the glycoconjugate residues of germ cells in apoptosis: Gal ß1,3-GalNAcα1, α-d-mannose, N-acetylgalactosamine and l-fucose. Furthermore, lectin specificity was observed for some specific germinal cells and in certain stages of apoptosis. It was also observed that one of these lectins (PNA) showed affinity for Sertoli cells undergoing apoptosis. Therefore, we conclude that the use of lectin histochemistry could be a very useful tool for studying apoptosis in the seminiferous epithelium because of the specificity shown towards germinal cells in pathological or experimentally induced epithelial depletion models.

[Coronary revascularization during cardiopulmonary resuscitation. The bridge code]. / Revascularización coronaria durante la resucitación cardiopulmonar. Código puente.

Cardiac arrest is one of the major current challenges, due to both its high incidence and mortality and the fact that it leads to severe brain dysfunction in over half of the survivors. The so-called coronary origin Bridge Code is presented, based on the international resuscitation recommendations (2005, 2010). In accordance with a series of strict predictive criteria, this code makes it possible to: (1) select refractory CPR patients with a high or very high presumption of underlying coronary cause; (2) evacuate the patient using mechanical chest compressors [LucasTM, Autopulse®], maintaining coronary and brain perfusion pressures; (3) allow coronary revascularization access during resuscitation maneuvering (PTCA during ongoing CPR); (4) induce early hypothermia; and (5) facilitate post-cardiac arrest intensive care. In the case of treatment failure, the quality of hemodynamic support makes it possible to establish a second bridge to non-heart beating organ donation.

[Early invasive strategy in non-ST-segment elevation acute coronary syndrome. The paradox continues]. / Uso de la estrategia invasiva precoz en el síndrome coronario agudo sin elevación de ST. La paradoja continúa.

OBJECTIVE: Observational studies have reported a paradoxical inverse relationship between the use of an early invasive strategy (EIS) and the risk of events in patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS). The study objectives are: 1) to examine the association between baseline risk in patients with NSTE ACS and the use of EIS; and 2) to identify some of the factors independently associated to the use of EIS. DESIGN: Retrospective cohort study. SETTING: Intensive care units participating in the SEMICYUC ARIAM Registry. PATIENTS: Consecutive patients admitted with a diagnosis of NSTE-ACS within 48 hours of evolution between the months of April-July 2010. INTERVENTIONS: None. MAIN OUTCOMES: Coronary angiography with or without angioplasty within 72 hours, risk stratification using the GRACE scale. RESULTS: We analyzed 543 patients with NSTE-ACS, of which 194 were of low risk, 170 intermediate risk and 179 high risk. The EIS was used in 62.4% of the patients at low risk, in 60.2% of those with intermediate risk, and in 49.7% of those at high risk (p for tendency 0.0144). The EIS was used preferentially in patients with low severity and comorbidity. In the logistic regression model, EIS was independently associated to the availability of a catheterization laboratory (OR 2.22 [CI 95% 1.55 to 3.19]), the presence of ST changes on ECG (OR 1.80 [1.23 to 2.64]), or the existence of a low risk of bleeding (OR 0.76 [0.66 to 0.88)]. Conversely, EIS was less prevalent in patients with diabetes (OR 0.60 [0.41 to 0.88]) or tachycardia upon admission (OR 0.54 [0 36 to 0.82]). CONCLUSIONS: In 2010 there remained a lesser relative use of EIS in patients at high risk, due in part to an increased risk of bleeding in these patients.

[Summary of the consensus document: "Clinical practice guide for the management of low cardiac output syndrome in the postoperative period of heart surgery"]. / Resumen del documento de consenso «Guías de práctica clínica para el manejo del síndrome de bajo gasto cardiaco en el postoperatorio de cirugía cardiaca¼

Low cardiac output syndrome is a potential complication in cardiac surgery patients and is associated with increased morbidity and mortality. This guide provides recommendations for the management of these patients, immediately after surgery and following admission to the ICU. The recommendations are grouped into different sections, addressing from the most basic concepts such as definition of the disorder to the different sections of basic and advanced monitoring, and culminating with the complex management of this syndrome. We propose an algorithm for initial management, as well as two others for ventricular failure (predominantly left or right). Most of the recommendations are based on expert consensus, due to the lack of randomized trials of adequate design and sample size in patients of this kind. The quality of evidence and strength of the recommendations were based on the GRADE methodology. The guide is presented as a list of recommendations (with the level of evidence for each recommendation) for each question on the selected topic. For each question, justification of the recommendations is then provided.

[Clinical practice guide for the management of low cardiac output syndrome in the postoperative period of heart surgery]. / Guías de práctica clínica para el manejo del síndrome de bajo gasto cardíaco en el postoperatorio de cirugía cardíaca.

The low cardiac output syndrome is a potential complication in cardiac surgery patients and associated with increased morbidity and mortality. This guide is to provide recommendations for the management of these patients, immediately after surgery, admitted to the ICU. The recommendations are grouped into different sections, trying to answer from the most basic concepts such as the definition to the different sections of basic and advanced monitoring and ending with the complex management of this syndrome. We propose an algorithm for initial management, as well as two other for ventricular failure (predominantly left or right). Most of the recommendations are based on expert consensus because of the lack of randomized trials of adequate design and sample size in this group of patients. The quality of evidence and strength of the recommendations were made following the GRADE methodology. The guide is presented as a list of recommendations (and level of evidence for each recommendation) for each question on the selected topic. Then for each question, we proceed to the justification of the recommendations.

[Tako-tsubo syndrome. Transient left ventricular dyskinesia. Presentation of our casuistics]. / Síndrome de tako-tsubo. Discinesia transitoria del ventrículo izquierdo. Presentación de nuestra casuística.

This syndrome was described in 1990. It is characterized by chest pain that simulates an acute coronary syndrome (ACS), with alterations in the ECG, but with normal coronary arteries. We present 16 patients admitted in our ICU, who met the criteria of transient left ventricular dysfunction syndrome (TLVDS). All but 1 patient were women, with age in general higher than 55 years. Chest pain was detected in the 75% of them. A total of 43% had emotional stress as 56% had an elevation of the ST segment, essentially anterolateral. The increase of the biomarkers was slight-to-moderate, with the exception of one patient in whom it was especially high. All of them had undergone a coronary arteriogram and ventriculography, and either septal or anterolateral dyskinesia had been detected, with normal ejection fraction. In 75% of the cases the dyskinesia had disappeared between 4 days to 6 weeks.

[Role of reactive oxygen species (ROS) on human spermatozoa and male infertility]. / Rôles des dérivés actifs de l'oxygène (DAO) sur les spermatozoïdes humains et infertilité masculine.

Pro- and antioxidant are balanced in the sperm environment. Reactive Oxygen Species (ROS) are essential to the acquisition of fertilizing ability and contribute to chromatin condensation, membrane remodeling and activation of intracellular signaling pathways, during epididymal maturation, capacitation, and acrosome reaction. However, endogenous and exogenous factors can upset that balance by stimulating ROS production and/or decreasing antioxidant defenses, a situation called oxidative stress. Oxidative stress is described as a major cause of male infertility. It induces membranes and nucleus alterations, resulting in loss of mobility and decline in sperm fertilizing ability. Those are risk factors for low fertility, abnormalities of preimplantation development, and miscarriages. Various methods exist for measuring the pro- and antioxidants status of sperm, yet are little used in routine for diagnostic purposes. Meanwhile, many studies have shown the beneficial effects of oral antioxidants supplementation, or addition to semen freezing medium, to prevent in vivo and limit in vitro the deleterious effects of ROS, respectively.

[Presence of parents in the emergency room during invasive procedures: do they prefer to be present?]. / Procedimientos invasivos en urgencias: ¿los familiares prefieren estar presentes?

INTRODUCTION: Parents are not usually present during procedures in the paediatric emergency room (ER), although an increasing number of them would like to. Our goal was to find out how parents felt about them being present in ER during procedures. MATERIAL AND METHODS: This is an observational study. Questionnaires were distributed among parents of patients in the ER during January and February 2007. Data included demographic questions as well as the opinion regarding their preference on being present during venipuncture, stitching, lumbar puncture or cardiopulmonary resuscitation. They were also asked about who should take the decision whether to allow the family to be present or not. RESULTS: A total of 98 questionnaires were analyzed. The median age of participants was 32 years-old, of which 84.5% would prefer to be present for venipuncture, 70.4% for stitching, 66.3% for lumbar puncture and 61.2% for cardiopulmonary resuscitation. Venipuncture was performed on 21% of the children, stitching on 4%, and lumbar puncture on 2%. There was no cardiopulmonary resuscitation. Parents considered that the decision about being present should be taken by the professional in 74% (venipuncture), 75% (stitching), 80% (lumbar puncture) and 81% (cardiopulmonary resuscitation). The mean age of the group that preferred to be present was lower (32 vs. 40 years; p = 0.039). CONCLUSIONS: Most parents surveyed preferred to be present during invasive procedures in ER. The more invasive the procedure is the higher reluctance from parents to be present. Most parents thought the decision should be taken by the health care professional, particularly when the procedure is more invasive.

Impairment of sperm maturation and capacitation due to diet-dependent cholesterol overload.

BACKGROUND: Lipid metabolic disorders (dyslipidemia) are constantly increasing in occidental societies and lead to the development of pathologies such as obesity, diabetes, and metabolic syndrome. It has been demonstrated that dyslipidemia can alter the reproductive function. Animal models have recently been used to show that the offspring of dyslipidemic males could also develop such pathologies and that the transgenerational transmission involved post-testicular sperm maturation. These data targeted the essential role of male gamete epididymal maturation and its importance for the health of the offspring. OBJECTIVES: This publication summarizes in the first place experimental data obtained using a mouse model of dyslipidemia-induced post-testicular infertility, knockout mice for the two isoforms of the 'Liver X Receptors' (Lxrα;ß-/- ), the major regulators of cholesterol homeostasis. The impact of a high cholesterol diet (HCD) on the protein YWHAZ (14-3-3 ζ or tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein Zeta) was also investigated in our model. MATERIALS AND METHODS: In our mouse model, when young fertile Lxrα;ß-/- males aged three months were fed four weeks with a HCD, they developed an epididymal phenotype leading to infertility. The level of sperm YWHAZ was evaluated by Western blot and its tyrosine phosphorylation state by immunoprecipitation followed by Western blot. RESULTS: Our data revealed that sperm lipid composition and structure were altered, leading to defects of the capacitation-associated signaling pathway. They also showed that both the level and the tyrosine phosphorylation state of YWHAZ were affected by the HCD in sperm cells from Lxrα;ß-/- males. DISCUSSION AND CONCLUSION: YWHAZ could be a new important regulator of capacitation-associated tyrosine phosphorylation and a marker of dyslipidemia-induced infertility.

Of vessels and cells: the spatial organization of the epididymal immune system.

BACKGROUND: One third of infertility cases in couples worldwide has an exclusive male origin and immune disorders, essentially due to repetitive infections, are emerging an cause of male infertility. As the place of sperm maturation, epididymis must be preserved from excessive immune responses that may arise following infections of the male genital tract. At the same time, epididymis must set and maintain a tolerogenic environment in order not to destroy sperm cells that enter the tissue at puberty, long after the immune system has been taught to recognize self pathogens. The immune cells that populate the epididymis have raised growing interest over the last thirty years but they may be not sufficient to understand the immune balance existing in this organ, between immune response to pathogens and tolerance to spermatozoa. Indeed, immune cells are the most motile cells in the organism and need blood and lymphatic vessels to traffic between lymphoid organs and sites of infection to induce efficient responses. OBJECTIVES: To review the literature on the blood and lymphatic vessels, and on the immune cells present at steady state in the rodent epididymis (rat and mouse). MATERIALS AND METHODS: PubMed database was searched for studies reporting on the spatial organization of the rodent epididymal vasculature and immune cell types at steady state. This search was combined with recent findings from our team. RESULTS: At steady state, the rodent epididymis presents with dense blood and lymphatic networks, and a large panel of immune cells distributed across the interstitum and epithelium along the organ. CONCLUSIONS: The immune system of the rodent epididymis is highly organized. Exploring its functions, especially in an infectious context, is the essential coming step before any transposition to human.

Increase of germ cell nuclear factor expression in globozoospermic Gopc-/- knockout mice.

BACKGROUND: Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC) is a Golgi protein that plays a role in vesicular transport and intracellular protein trafficking and degradation. Mice deficient in GOPC protein have globozoospermia and are infertile. The germ cell nuclear factor (GCNF) is a member of the nuclear receptor superfamily which is expressed in male germ cells, from spermatocytes and spermatids, both in the nucleus and the acrosomal region. It is not known if its expression could be altered in Gopc-/- mice with defective acrosomes. OBJECTIVES: The aim of the present work was to analyze the distribution of GCNF protein in spermatids of Gopc-/- knockout mice. MATERIALS AND METHODS: We have analyzed the expression and distribution during spermatogenesis of GCNF and its deregulation in Gopc-/- mutant mice by RT-qPCR, Western blot, immunohistochemistry and immunogold. RESULTS: Germ cell nuclear factor was localized in the nucleus of all the cell types in the seminiferous tubules. Despite being a nuclear protein, it was also located in the acrosome and in the manchette of elongating spermatids. We have found that in the absence of GOPC, the expression of GCNF was increased in the nucleus of spermatocytes, mainly in leptotene, and in the nucleus and the manchette during the spermatid elongation. DISCUSSION AND CONCLUSION: Gopc-/- mice have defective acrosome and manchette. The manchette is involved in the transport of proteins through the cytoplasm and the nucleus. Considering that the GCNF protein is normally transported to the acrosome and the nucleus, it can be thought that transport deficiencies in Gopc-/- mice are responsible for the increased expression of this protein.

Identification of sperm antigens as a first step towards the generation of a contraceptive vaccine to decrease fossorial water vole Arvicola terrestris Scherman proliferations.

Immunocontraceptive strategies have proved to be efficient in controlling fertility of various mammalian species. In the present study we have made the first steps towards the identification of Arvicola terrestris sperm antigens that could be used as targets in the development of a contraceptive vaccine to limit the proliferations of this pest rodent. Rabbit-raised polyclonal antisera directed against complete A. terrestris spermatozoa were used to identify and characterize on 2D-gels coupled with a MALDI-TOF mass spectrometry analysis A. terrestris sperm proteins. Amongst the proteins pinpointed by this approach some were further investigated based on their tissue- and/or sperm-specific expression, and their relevance to fertility or sperm/egg interaction. In parallel, three proteins that have been already reported in the literature to be appropriate targets for the development of contraceptive vaccines in other mammalian species have also been looked for in A. terrestris. With the selected protein targets, a reverse-PCR approach using degenerate primers was employed to amplify corresponding A. terrestris cDNAs. After conceptual translation and sequence alignment, different proteins were studied to determine zones with sufficient sequence divergence and of antigenic/immunogenic nature that could be used in future assays to immunize animals.

Correction of chin ptosis.

Chin ptosis is described as a descent of the soft tissue from the symphyseal region to a position under the lower contour of the mandible. Given its multifactorial causes, treatment must be determined on a patient-by-patient basis. While augmentation of the submental crease is a versatile option for the correction of chin ptosis, this only corrects the soft tissue component. A technical modification to treat dynamic chin ptosis, associated with bone reduction in the mandibular symphysis, is presented here.

Morphofunctional basis of the different types of angiogenesis and formation of postnatal angiogenesis-related secondary structures.

We review the morpho-functional basis of the different types of angiogenesis and report our observations, including the formation of angiogenesis-related secondary structures. First of all, we consider the following issues: a) conceptual differences between angiogenesis and vasculogenesis, b) incidence of angiogenesis in pre- and postnatal life, c) regions of vascular tree with angiogenic capacity, d) cells (endothelial cells, pericytes, CD34+ adventitial stromal cells of the microvasculature and inflammatory cells) and extracellular matrix components involved in angiogenesis, e) events associated with angiogenesis, f) different types of angiogenesis, including sprouting and intussusceptive angiogenesis, and other angiogenic or vascularization forms arising from endothelial precursor cells (postnatal vasculogenesis), vasculogenesis mimicry, vessel co-option and piecemeal angiogenesis. Subsequently, we consider the specific morpho-functional characteristics of each type of angiogenesis. In sprouting angiogenesis, we grouped the events in three phases: a) activation phase, which includes vasodilation and increased permeability, EC, pericyte and CD34+ adventitial stromal cell activation, and recruitment and activation of inflammatory cells, b) sprouting phase, encompassing EC migration (concept and characteristics of endothelial tip cells, tip cell selection, lateral inhibition, localized filopodia formation, basal lamina degradation and extracellular changes facilitating EC migration), EC proliferation (concept of endothelial stalk cells), pericyte mobilization, proliferation, recruitment and changes in CD34+ adventitial stromal cells and inflammatory cells, tubulogenesis, formation of a new basal lamina, and vascular anastomosis with capillary loop formation, and c) vascular remodelling and stabilization phase (concept of phalanx cells). Subsequently, the concept, incidence, events and mechanisms are considered in the other forms of angiogenesis. Finally, we contribute the formation of postnatal angiogenesis-related secondary structures: a) intravascular structures through piecemeal angiogenesis, including intravascular papillae in vessel tumours and pseudotumours (intravascular papillary endothelial hyperplasia, vascular transformation of the sinus in lymph nodes, papillary intralymphatic angioendothelioma or Dabska tumour, retiform hemangioendothelioma, hemangiosarcoma and lymphangiosarcoma), vascular septa in hemorrhoidal veins and intravascular projections in some tumours; b) arterial intimal thickening; c) intravascular tumours and pseudotumours (e.g. intravenous pyogenic granulomas and intravascular myopericytoma); d) vascular glomeruloid proliferations; and e) pseudopalisading necrosis in glioblastoma multiform.