Transradial Prostatic Artery Embolization as a Salvage Procedure in a Patient With Severe Deformities and Refractory Hematuria of Prostatic Origin.

Benign prostatic hyperplasia is a common condition causing urinary symptoms in older men. It can sometimes lead to hematuria of prostatic origin, due to increased vascularity of the enlarged gland. If this type of hematuria is severe and refractory to conservative measures, it can be life-threatening. Prostatic artery embolization (PAE) serves as a minimally invasive alternative to traditional surgical interventions, particularly in patients with comorbidities and contraindications to surgery. We present a case of a 79-year-old male with refractory hematuria of prostatic origin (RHPO), multiple comorbidities, and significant deformities of the left upper and both lower limbs. The patient was treated with PAE via the right radial artery, a less common approach in interventional radiology. The procedure was successful and led to a complete resolution of hematuria, with no complications. This report highlights the importance of adapting treatment for complex patients and shows that PAE can be safe and effective in such cases.

Psychological and sexological assessment of patients with chronic prostatitis.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by a multiform clinical presentation requiring a differentiated treatment based on different phenotypes including the psychosocial and sexual domains. The aim of this study was assessing the complex correlations between somatic, psychological, and sexual symptoms of CP/CPPS patients. MATERIALS AND METHODS: We performed a cross-sectional study on patients attending a Prostatitis Clinic. Patients were administered the following questionnaires: National Institutes of Health- Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF), Premature Ejaculation Diagnostic Tool (PEDT), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Oxford Happiness Questionnaire (OHQ), and Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A). RESULTS: Linear regression analyses show highly significant correlations between scores of the NIH-CPSI and the scores of the GAD-7, PHQ-9 and OHQ psychometric questionnaires. IPSS scores correlate significantly with the psychometric scores only when a non-parametric analysis is performed. IIEF and PEDT sexual function scores did not correlate with any of the psychometric tests. NIH-CPSI scores correlate positively with most of the TEMPS-A profiles but the hyperthymic profile correlated negatively with the total and QoL NIH-CPSI and with PEDT scores. CONCLUSIONS: Scores measuring anxiety, depression, and psychological well-being in patients with CP/CPPS are strictly correlated with prostatitis-like symptoms although they are poorly correlated with symptoms of prostatism, as measured by IPSS, and not correlated with scores of sexual dysfunctions, as measured by IIEF and PEDT. A hyperthymic temperament may increase resilience against the disease.

Ki-67 is necessary during DNA replication for fork protection and genome stability.

BACKGROUND: The proliferation antigen Ki-67 has been widely used in clinical settings for cancer staging for many years, but investigations on its biological functions have lagged. Recently, Ki-67 has been shown to regulate both the composition of the chromosome periphery and chromosome behaviour in mitosis as well as to play a role in heterochromatin organisation and gene transcription. However, how the different roles for Ki-67 across the cell cycle are regulated and coordinated remain poorly understood. The progress towards understanding Ki-67 function have been limited by the tools available to deplete the protein, coupled to its abundance and fluctuation during the cell cycle. RESULTS: Here, we use a doxycycline-inducible E3 ligase together with an auxin-inducible degron tag to achieve a rapid, acute and homogeneous degradation of Ki-67 in HCT116 cells. This system, coupled with APEX2 proteomics and phospho-proteomics approaches, allows us to show that Ki-67 plays a role during DNA replication. In its absence, DNA replication is severely delayed, the replication machinery is unloaded, causing DNA damage that is not sensed by the canonical pathways and dependent on HUWE1 ligase. This leads to defects in replication and sister chromatids cohesion, but it also triggers an interferon response mediated by the cGAS/STING pathway in all the cell lines tested. CONCLUSIONS: We unveil a new function of Ki-67 in DNA replication and genome maintenance that is independent of its previously known role in mitosis and gene regulation.

Cell Cycle-Specific Protein Phosphatase 1 (PP1) Substrates Identification Using Genetically Modified Cell Lines.

The identification of protein phosphatase 1 (PP1) holoenzyme substrates has proven to be a challenging task. PP1 can form different holoenzyme complexes with a variety of regulatory subunits, and many of those are cell cycle regulated. Although several methods have been used to identify PP1 substrates, their cell cycle specificity is still an unmet need. Here, we present a new strategy to investigate PP1 substrates throughout the cell cycle using clustered regularly interspersed short palindromic repeats (CRISPR)-Cas9 genome editing and generate cell lines with endogenously tagged PP1 regulatory subunit (regulatory interactor of protein phosphatase one, RIPPO). RIPPOs are tagged with the auxin-inducible degron (AID) or ascorbate peroxidase 2 (APEX2) modules, and PP1 substrate identification is conducted by SILAC proteomic-based approaches. Proteins in close proximity to RIPPOs are first identified through mass spectrometry (MS) analyses using the APEX2 system; then a list of differentially phosphorylated proteins upon RIPPOs rapid degradation (achieved via the AID system) is compiled via SILAC phospho-mass spectrometry. The "in silico" overlap between the two proteomes will be enriched for PP1 putative substrates. Several methods including fluorescence resonance energy transfer (FRET), proximity ligation assays (PLA), and in vitro assays can be used as substrate validations approaches.

Treatment of urge incontinence in postmenopausal women: A systematic review.

BACKGROUND: Urinary incontinence and other urinary symptoms tend to be frequent at menopause because of hormonal modifications and aging. Urinary symptoms are associated with the genitourinary syndrome of menopause which is characterized by physical changes of the vulva, vagina and lower urinary tract. The treatment strategies for postmenopausal urinary incontinence are various and may include estrogens, anticholinergics, and pelvic floor muscle training. A comparison of these treatments is difficult due to the heterogeneity of adopted protocols. We systematically reviewed the evidence from randomized controlled trials (RCTs) focusing on treatment of postmenopausal women with urge incontinence. METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE databases for randomized controlled trials (RCTs) reporting results of treatments for postmenopausal urinary urge incontinence. Odds ratios for improvement of urinary incontinence were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 248 records retrieved, 35 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared with placebo, systemic estrogens were associated with decreased odds of improving urinary incontinence in postmenopausal women (OR = 0.74, 95% CI: 0.61-0.91, 7 series, 17132 participants, Z = 2.89, P = 0.004, I2 = 72%). In most studies, no significant improvement in urinary symptoms was observed in patients treated with local estrogens, although they showed to be helpful in improving vaginal symptoms. Vitamin D, phytoestrogens and estrogen modulators were not effective in improving symptoms of incontinence and other symptoms of genitourinary menopause syndrome or yielded contradictory results. A randomized controlled trial demonstrated that oxybutynin was significantly better than placebo at improving postmenopausal urgency and urge incontinence. The combination of anticholinergics with local estrogens has not been shown to be more effective than anticholinergics alone in improving urinary incontinence symptoms in postmenopausal women. Physical therapy showed an overall positive outcome on postmenopausal urinary incontinence symptoms, although such evidence should be further validated in the frame of quality RCTs. CONCLUSIONS: The evidence for effective treatment of postmenopausal urinary incontinence is still lacking. Welldesigned large studies having subjective and objective improvement primary endpoints in postmenopausal urinary incontinence are needed. At present, a combination of different treatments tailored to the characteristics of the individual patient can be suggested.

Angiographic Imaging of Prostatic Artery Origin in a Greek Population and Correlation With Technical and Clinical Aspects of Prostatic Artery Embolization.

Background This study aimed, first, to angiographically investigate and analyze prostatic artery (PA) origin in a Greek male population with benign prostatic hyperplasia (BPH) treated with prostatic artery embolization (PAE) and, second, to correlate prostatic arterial anatomy with technical and clinical aspects of PAE. Methodology This was a retrospective study of BPH patients who underwent PAE in a single tertiary center in Greece from June 2019 to July 2022. For the first part of the study, PA was imaged with computed tomography angiography (CTA) before PAE and with digital subtraction angiography (DSA) during PAE in all patients. A widely accepted system for the classification of PA origin was applied. Type I, a common origin of PA and superior vesical artery (SVA) from the anterior division of internal iliac artery (IIA). Type II, PA originating from the anterior division of IIA, separate from, and inferior to SVA. Type III, the origin of PA from the obturator artery. Type IV, the origin of PA from the internal pudendal artery. Type V, rarer origins of PA. For the second part of the study, a subgroup of patients from the first part (treated with the same PAE protocol and free of vascular pathology that could have interfered with the technical success of PAE) was selected. In this subgroup, differences in PA origin were correlated with technical aspects (feasibility of catheterization of PA, fluoroscopy time (FT), dose area product (DAP)) and clinical outcomes of PAE. Results After the exclusion of four patients, 159 patients were included in the first part of the study. From a total of 355 PAs, 110 (31%) were compatible with type I, 58 (16.3%) type II, 45 (12.7%) type III, 110 (31%) type IV, and 32 (9%) type V. PA origin from an accessory internal pudendal artery was the most common among the rare origins of type V. Regarding the second part of the study (a subgroup of 101 patients selected to facilitate comparisons between the different types of PA origin), type I was associated with significantly more incidences of failed or difficult catheterization of the PA compared to all other types combined (27/64 vs. 18/138, p < 0.001). Types III, IV, and V showed a relatively low degree of technical difficulty. Patients with type I PA origin of at least one pelvic side (subgroup (I), n = 48) had significantly longer FT and DAP compared to the rest (subgroup (O), n = 53). Clinical success rates of PAE were slightly lower for the subgroup (I), although the difference was not statistically significant (75.8% vs. 83.8% at 18 months post-PAE, p = 0.137). No major complications were observed. Conclusions This is the first study of PA origin in Greece. It was demonstrated that types I and IV of PA origin were the most common and had the same prevalence. Type I showed significantly higher technical difficulty compared to the others, but had no significant impact on the clinical outcomes of PAE.

Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis.

Although SGLT2 inhibitors have been initially employed in the treatment of type 2 diabetes, their clinical use was later extended to the treatment of other conditions such as heart failure, chronic kidney disease and obesity. In patients with type 2 diabetes, the administration of SGLT2 inhibitors has been associated with an increased incidence of urogenital infections, which may be linked to high glucose levels in the urine. The rate of urogenital side effects may be different in non-diabetic patients. The aim of this study was to review the risk of urogenital infections in non-diabetic patients taking SGLT2 inhibitors. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE for randomized controlled trials (RCTs) reporting urogenital adverse effects in non-diabetic patients treated with SGLT2 inhibitors. Odds ratios for urogenital infections were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 387 citations retrieved, 12 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared to placebo, SGLT2 inhibitors were associated with increased odds of genital infections (OR 3.01, 95% CI: 1.93- 4.68, 9 series, 7326 participants, Z = 5.74, p < 0.0001, I2 = 0%) as well as urinary tract infections (OR 1.33, 95% CI: 1.13-1.57, 9 series, 7326 participants, Z = 4.05, p < 0.0001, I2 = 0%). When four trials investigating the effects of SGLT2 inhibitors in populations including both diabetic and non-diabetic patients were considered, administration of SGLT2 inhibitors in diabetic patients was associated with significantly higher odds of genital infections but not urinary tract infections compared to patients without type 2 diabetes. In patients taking placebo, the odds for urinary tract infections were significantly increased in diabetic patients compared to non-diabetic patients. CONCLUSIONS: The risk of genital infections is increased also in non-diabetic patients taking SGLT2 inhibitors although at a lesser extent that in diabetics. A careful assessment of the local anatomical conditions and of the history of previous urogenital infections is desirable to select those patients who need more intense follow-up, possibly combined with prophylactic measures of infections during treatment with SGLT2 inhibitors.

Chronic prostatitis and related psychological problems. Which came first: The chicken or the egg? A systematic review.

INTRODUCTION/AIM: A spectrum of psychological problems is commonly found in CP/CPPS patients, though it is not yet clear whether, a priori, psychological dysfunctions are the cause of these pain syndromes, or whether these pain conditions are themselves causing psychological disturbances. In this article we present the current perspective on the impact of psychological problems in chronic prostatitis syndromes and we discuss the implications thereof from a clinical perspective. MATERIALS AND METHODS: A database and a manual search were conducted in the MEDLINE database of the National Library of Medicine, EMBASE, and other libraries using the key words "prostatitis syndromes", "chronic bacterial prostatitis", "chronic pelvic pain", in various combinations with the terms "psychological issues", "depression" "anxiety", "stress", "unhappiness", "cognitive status" and "personality". Two independent reviewers performed data extraction. We included clinical studies with available information on chronic prostatitis and related psychological conditions. We considered full-text written papers. We excluded reviews and case reports. In order to reduce the risk of bias we analyzed only studies including patients with confirmed CBP or CP/CPPS. Bibliographic information in the selected publications was checked for relevant records not included in the initial search. RESULTS: Database search allowed us to retrieve 638 studies to which we added to 16 additional studies retrieved by hand-searching. After screening, 34 relevant papers were identified for thorough review. Most studies included patients with chronic pelvic pain and prostatitis-like symptoms, whereas a smaller number of studies included patients with methodologically con- firmed CP/CPPS including studies with a microbiologically confirmed diagnosis of CBP. The psychosocial factors examined in the selected studies include pain, catastrophizing, stress, personality factors and social aspects. Comorbid psychiatric disorders evidenced in the studies included depression, anxiety and trauma-related disorders, somatization disorders, and substance abuse. Some studies investigated the association of pain with each individual psychological disturbance, while others examined the impact of pain in association with the overall quality of life. Sample size, study design and diagnostic measures varied among studies. CONCLUSIONS: Despite limitations and variations in sample size, study design and diagnostic measures in all included studies, a relation between chronic prostatitis and psychological problems is a consistent finding. The existing evidence does not permit to definitely conclude whether psychological problems are a risk factor for CP/CPPS or whether they represent an array of symptoms that are associated with the exacerbation of this disease.

Percutaneous thrombin injection under contrast-enhanced ultrasound guidance to control active extravasation not associated with pseudoaneurysm.

The technique of percutaneous thrombin injection (PTI) under contrast-enhanced ultrasound (CEUS) guidance for control of acute hemorrhage-active extravasation not associated with pseudoaneurysm is demonstrated in three cases: 1) Massive spontaneous retroperitoneal hematoma in a patient with multiple comorbidities. Contrast-enhanced computed tomography (CT) showed extensive active extravasation, which was only partially controlled by transarterial embolization. CEUS was performed in the angiography suite. Contrary to unenhanced US and colour Doppler US (CDUS), CEUS confirmed persistent extravasation; CEUS-guided PTI was performed immediately thereafter. 2) Large rectus sheath hematoma in a patient on anticoagulant therapy. Contrast-enhanced CT and unenhanced US/CD could not definitely diagnose extravasation. CEUS clearly showed extravasation and was used for guidance of PTI. 3) Chest wall hematoma complicating central venous catheter placement in a patient with coronavirus on anticoagulant therapy. CDUS was inconclusive. CEUS was performed at the bedside, clearly showed active extravasation, and was used for guidance of PTI. In all three cases, post-PTI CEUS confirmed the absence of residual enhancement of the hematomas, and the hemodynamic status of the patients improved. PTI appears to be effective in selected cases of hematomas associated with active extravasation. In this context, CEUS may be the most suitable modality for guidance and for an immediate evaluation of the treatment effect.

CCDC86 is a novel Ki-67-interacting protein important for cell division.

The chromosome periphery is a network of proteins and RNAs that coats the outer surface of mitotic chromosomes. Despite the identification of new components, the functions of this complex compartment are poorly characterised. In this study, we identified a novel chromosome periphery-associated protein, CCDC86 (also known as cyclon). Using a combination of RNA interference, microscopy and biochemistry, we studied the functions of CCDC86 in mitosis. CCDC86 depletion resulted in partial disorganisation of the chromosome periphery with alterations in the localisation of Ki-67 (also known as MKI67) and nucleolin (NCL), and the formation of abnormal cytoplasmic aggregates. Furthermore, CCDC86-depleted cells displayed errors in chromosome alignment, altered spindle length and increased apoptosis. These results suggest that, within the chromosome periphery, different subcomplexes that include CCDC86, nucleolin and B23 (nucleophosmin or NPM1) are required for mitotic spindle regulation and correct kinetochore-microtubule attachments, thus contributing to chromosome segregation in mitosis. Moreover, we identified CCDC86 as a MYCN-regulated gene, the expression levels of which represent a powerful marker for prognostic outcomes in neuroblastoma.

Risk of urinary stone formation associated to proton pump inhibitors: A systematic review and metanalysis.

OBJECTIVE: Proton pump inhibitors are widely used as treatment of acid-related disorders. They are considered safe although their long-term use has been associated with some adverse effects including an increased propensity for urinary calculi formation. The aim of this study was to systematically review available data from studies evaluating the association of PPIs and nephrolithiasis. MATERIALS AND METHODS: We searched two electronic databases (PubMed and EMBASE) for cohort studies or case-control studies evaluating the relationship between treatment with proton pump inhibitors and the risk of stone formation published up to 31 October 2022. The overall association of PPIs and urinary calculi was analyzed using a random effects model (RevMan5). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: A total of 550 studies were retrieved; 7 were selected by title and abstract screening; after removal of duplicates, 4 records were evaluated by full-text examination. An additional study was retrieved by handsearching the references included in screened studies. In the unadjusted analysis, the odds of urinary calculi were greater in subjects taking PPIs compared to controls (unadjusted OR = 2.10, 95% CI 1.74-2.52, p < 0.00001). The pooled odds ratio of two case-control studies confirmed that use of PPIs increased the odds of urinary calculi compared with non-use (OR 2.44, 95% CI 2.29 to 2.61). Pooled analysis of three cohort studies evaluating incident nephrolithiasis showed an overall hazard ratio estimate of 1.34 (95% CI = 1.28-1.40). One study found lower urinary citrate and urinary magnesium levels in subjects exposed to PPIs. The Newcastle-Ottawa Quality Assessment Scale scores ranged between 6 and 8. CONCLUSIONS: PPIs showed an association with urinary calculi in patients included in the studies included in this review. If these data will be confirmed in adequately powered randomized trials, clinicians may consider limiting the long-term use of PPIs, to avoid unnecessary prolongation of treatment. Urinary magnesium and citrate should be evaluated in renal stone forming patients taking PPIs to supplement their intake when requested.

Efficacy of overactive neurogenic bladder treatment: A systematic review of randomized controlled trials.

BACKGROUND: Overactive bladder (OAB) symptoms of frequency, urgency and urge incontinence are frequently associated with known neurological diseases like multiple sclerosis (MS), spinal cord injury (SCI), Parkinson's disease (PD), stroke. OBJECTIVE: The aim of our study was to review the efficacy of pharmacological and non-pharmacological treatments for neurogenic overactive bladder. MATERIALS AND METHODS: We searched two electronic databases (PubMed and EMBASE) for randomized controlled trials focusing on pharmacological and non-pharmacological medical treatments for overactive bladder symptoms associated with neurological diseases published up to 30 April 2022. RESULTS: A total of 157 articles were retrieved; 94 were selected by title and abstract screening; after removal of 17 duplicates, 77 records were evaluated by full-text examination. Sixty-two studies were finally selected. The articles selected for review focused on the following interventions: anticholinergics (n = 9), mirabegron (n = 5), comparison of different drugs (n = 3), cannabinoids (n = 2), intravesical instillations (n = 3), botulinum toxin (n = 16), transcutaneous tibial nerve stimulation (TTNS) (n = 6), acupuncture (n = 2), transcutaneous electrical nerve stimulation TENS (n = 4), pelvic floor muscle training (PFMT) (n = 10), others (n = 2). Anticholinergics were more effective than placebo in decreasing the number of daily voids in patients with PD (mean difference [MD]- 1.16, 95 % CI - 1.80 to - 0.52, 2 trials, 86 patients, p < 0.004), but no significant difference from baseline was found for incontinence episodes and nocturia. Mirabegron was more effective than placebo in increasing the cystometric capacity in patients with MS (mean difference [MD] 89.89 mL, 95 % CI 29.76 to 150.01, 2 trials, 98 patients, p < 0.003) but no significant difference was observed for symptom scores and bladder diary parameters. TTNS was more effective than its sham-control in decreasing the number of nocturia episodes (MD -1.40, 95 % CI -2.39 to -0.42, 2 trials, 53 patients, p < 0.005) but no significant changes of OAB symptom scores were reported. PFMT was more effective than conservative advice in decreasing the ICIQ symptom score (MD, -1.12, 95 % CI -2.13 to -0.11, 2 trials, 91 patients, p = 0.03), although the number of incontinence episodes was not significantly different between groups. CONCLUSIONS: The results of the meta-analysis demonstrate a moderate efficacy of all considered treatments without proving the superiority of one therapy over the others. Combination treatment using different pharmacological and non-pharmacological therapies could achieve the best clinical efficacy due to the favorable combination of the different mechanisms of action. This could be associated with fewer side effects due to drug dosage reduction. These data are only provisional and should be considered with caution, due to the few studies included in metaanalysis and to the small number of patients.

A Retrospective, Single-Center Study of Technical-Procedural Factors Affecting Radiation Dose During Prostatic Artery Embolization.

Introduction This study aims to evaluate the effect of technical-procedural factors on radiation dose during prostatic artery embolization (PAE). Methods This was a single-center, retrospective study of 59 patients with benign prostatic hyperplasia (BPH) who underwent prostatic artery embolization from March 2020 to September 2021. Computed tomography angiography (CTA) was performed for vascular planning prior to PAE in all patients. The effect of the following techniques on the dose area product (DAP) of PAE was evaluated: application of low-dose protocol (LDP) for digital subtraction angiography (DSA), reduction of oblique projections by performing PAE of at least one pelvic side utilizing anteroposterior projections only (AP-PAE), utilization of "roadmap" technique instead of DSA for the delineation of pelvic arterial anatomy (RDMP-PAE), and cone-beam CT (CBCT). The impact of the patient's body mass index (BMI) on DAP was also calculated. The effective dose (ED) of PAE and pre-PAE CTA was calculated from DAP and from dose length products, respectively, using appropriate conversion factors. Results For the entire study population (n = 59), the mean DAP of PAE was 16,424.7 ± 8,019 µGy‧m2. On simple regression analysis, LDP, AP-PAE, and RDMP-PAE significantly contributed to DAP reduction during PAE (30% (p = 0.004), 26.7% (p = 0.013), and 31.2% (p = 0.004), respectively). On multiple regression, LDP and AP-PAE maintained their significant effect (p = 0.002 and p = 0.006, respectively). CBCT was associated with a not statistically significant increase in DAP (10.1%) (p = 0.555). The ED of CTA represented 21.2% ± 10.6% of the ED of PAE. Conclusion Of the four studied factors, LDP, AP-PAE, and RDMP-PAE proved to be relatively simple and widely available techniques that could limit radiation exposure of both the operators and the patients during PAE. The contribution of planning CTA to the overall radiation exposure of patients undergoing PAE appears to be not negligible.

Safety considerations with new antibacterial approaches for chronic bacterial prostatitis.

INTRODUCTION: Chronic bacterial prostatitis (CBP) is a difficult-to-eradicate infection. Antibacterial therapy with currently licensed agents is hindered due to the increasing emergence of pathogen resistance worldwide and to frequent infection relapse. With limited treatment options, physicians are investigating new agents, which, however, may raise safety concerns. AREAS COVERED: Antibacterial agents currently licensed for CBP were not considered. Available reports about the safety and efficacy of antibacterial agents that have been clinically tested or tentatively used to treat CBP in single cases were evaluated. This review also focused on agents targeting Gram-positive pathogens, whose prevalence as causative agents of CBP is increasing. EXPERT OPINION: (i) Most antibacterial agents considered in this review have been administered off-label in the interest of patients, and their use requires particular caution. (ii) Reports describing the usage of many of the drugs reviewed here are still scant, and readers should be warned of the limited published evidence supporting therapy for CBP with these agents. (iii) As treatment must extend over several weeks, medium-term adverse events may occur and therapy should be individualized, taking into account the dosage and the potential toxicity of each specific antibiotic. Regarding dangerous drug-drug interactions, particular attention should be paid to the risk of ECG-QT-interval elongation.

Drug-induced gynecomastia: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: To review the evidence concerning treatment-related gynecomastia in patients taking spironolactone, antiandrogens, 5 alpha-reductase inhibitors, lipid-lowering and psychotropic drugs. MATERIAL AND METHODS: A search of Medline and EMBASE was performed up to 30 June 2021. We included randomized controlled trials comparing the effects of a drug belonging to these classes versus placebo or versus a drug of the same class. RESULTS: A total of 32 randomized controlled trials were included in the final review. There was an increased odds of gynecomastia in men receiving antiandrogens (OR = 17.38, 95% CI: 11.26 to 26.82; 6 trials, 9599 participants) and 5 alpha-reductase inhibitors compared to controls (OR = 1.77, 95% CI: 1.53 to 2.06; 7 series out of 6 trials, 34860 participants). The use of spironolactone in mixed gender populations was characterized by significantly higher odds of having gynecomastia compared to controls (OR = 8.39, 95% CI: 5.03 to 13.99; 14 trials, 3745 participants). No placebo-controlled trials focusing on the risk of gynecomastia in patients taking antipsychotic drugs was available, although there was a significant difference in the odds of having gynecomastia in a comparison between risperidone and quetiapine (OR = 4.32, 95% CI: 1.31 to 14.27; 3 trials, 343 participants). Limited evidence about the effects of statins on mammary glands was found. CONCLUSIONS: Antiandrogens and to a lesser extent 5 alphareductase inhibitors and spironolactone are associated with an increased risk of developing gynecomastia. Such effect can be explained by a modification of the testosterone to estradiol ratio. Gynecomastia (and galactorrhea) associated to the use of conventional and certain atypical antipsychotics can be related to high prolactin levels.

Chromosome clustering in mitosis by the nuclear protein Ki-67.

Ki-67 is highly expressed in proliferating cells, a characteristic that made the protein a very important proliferation marker widely used in the clinic. However, the molecular functions and properties of Ki-67 remained quite obscure for a long time. Only recently important discoveries have shed some light on its function and shown that Ki-67 has a major role in the formation of mitotic chromosome periphery compartment, it is associated with protein phosphatase one (PP1) and regulates chromatin function in interphase and mitosis. In this review, we discuss the role of Ki-67 during cell division. Specifically, we focus on the importance of Ki-67 in chromosome individualisation at mitotic entry (prometaphase) and its contribution to chromosome clustering and nuclear remodelling during mitotic exit.

Clinical Validation of the Greek Version of the Acute Cystitis Symptom Score (ACSS)-Part II.

The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for the clinical diagnosis and patient-reported outcome (PRO) in women with acute uncomplicated cystitis (AC). The aim of the current study (part II) is the clinical validation of the Greek ACSS questionnaire. After linguistic validation according to internationally accepted guidelines and cognitive assessment (part I), the clinical validation was performed by using the Greek ACSS study version in 92 evaluable female participants including 53 patients with symptoms suspicious of AC and 39 controls. The clinical outcome using the ACSS questionnaire at different points in time after the start of treatment was demonstrated as well. The age (mean ± SD) of the 53 patients (44.7 ± 17.0 years) and 39 controls (49.3 ± 15.9 years) and their additional conditions at baseline visits, such as menstruation, premenstrual syndrome, pregnancy, menopause, diabetes mellitus, were comparable. There was, however, a significant difference (p < 0.001) between patients and controls at baseline visit regarding sum score of the ACSS domains, such as typical symptoms and quality of life. The clinical outcome of up to 7 days showed a fast reduction of the symptom scores and improvement of quality of life. The optimal thresholds for the patient-reported outcome of successful therapy could be established. The linguistically and clinically validated Greek ACSS questionnaire can now be used for clinical or epidemiological studies and also for patients' self-diagnosis of AC and as a PRO measure tool.

One, No One and One Hundred Thousand: Patterns of chronic prostatic inflammation and infection.

Chronic prostatic inflammation may be classified into three types that share similar symptoms and are distinguished on the basis of microbiological findings. In the present study, consecutive cases of chronic prostatic inflammation and infection were retrospectively reviewed in order to explore the clinical course and long-term outcomes. The cohort consisted of patients with symptoms of prostatitis who visited the Urology Clinic of the Tzaneion Hospital (Piraeus, Greece) between March 2009 and March 2019. The patients were subjected to the Meares and Stamey '4-glass' test and patients with febrile prostatitis were evaluated with a single mid-stream 'clean' urine sample culture. Bacterial identification was performed using the Vitek 2 Compact system and the sensitivity test with the disc and the Vitek 2 system. A total of 656 patients with prostatitis-like symptoms with 1,783 visits for investigation and follow-up were reviewed and patients were divided into two major groups. Group 1 consisted of 549 cases with a single set of chronic prostatitis (CP)-like symptoms assessed in up to three visits. National Institutes of Health (NIH) category II CP (NIH-II) was most frequently diagnosed in those patients (37,6%). At the follow-up, 125 patients were identified as having a type of CP different from that determined initially. Group 2 (107 cases) had recurring episodes of prostatitis-like symptoms assessed or confirmed over the course of 4-18 visits. Most patients (54.2%) were initially diagnosed with NIH-II followed by disease-free periods and recurrence/reinfection or by shifts to NHI-IIIB. In conclusion, CP remains a poorly understood n medical condition characterized by a variety of clinical manifestations and by transitions between different CP classes during its course.

Spectrum of Causative Pathogens and Resistance Rates to Antibacterial Agents in Bacterial Prostatitis.

OBJECTIVE: To evaluate spectrum and resistance rates to antibacterial agents in causative pathogens of bacterial prostatitis in patients from Southern Europe, the Middle East, and Africa. MATERIALS: 1027 isolates from cultures of urine or expressed prostatic secretion, post-massage urine or seminal fluid, or urethral samples were considered. RESULTS: Escherichia coli (32%) and Enterococcus spp. (21%) were the most common isolates. Other Gram-negative, Gram-positive, and atypical pathogens accounted for 22%, 20%, and 5%, respectively. Resistance was <15% for piperacillin/tazobactam and carbapenems (both Gram-negative and -positive pathogens); <5% for glycopeptides against Gram-positive; 7%, 14%, and 20% for aminoglycosides, fosfomycin, and macrolides against Gram-negative pathogens, respectively; 10% for amoxicillin/clavulanate against Gram-positive pathogens; <20% for cephalosporins and fluoroquinolones against to Gram-negative pathogens (higher against Gram-positive pathogens); none for macrolides against atypical pathogens, but 20% and 27% for fluoroquinolones and tetracyclines. In West Africa, the resistance rates were generally higher, although the highest rates for ampicillin, cephalosporins, and fluoroquinolones were observed in the Gulf area. Lower rates were observed in Southeastern Europe. CONCLUSIONS: Resistance to antibiotics is a health problem requiring local health authorities to combat this phenomenon. Knowledge of the spectrum of pathogens and antibiotic resistance rates is crucial to assess local guidelines for the treatment of prostatitis.