[Chronic prostatitis/chronic pelvic pain syndrome]. / Chronische Prostatitis/chronisches Beckenschmerzsyndrom.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is defined as chronic pain or discomfort in the pelvic region for at least 3 of the past 6 months. It is variably associated with lower urinary tract symptoms, psychosocial consequences, and sexual dysfunction. Specific test systems or biomarkers for a definitive diagnosis are still not available. The purposes of the basic diagnostic assessment are to determine the individual spectrum of symptoms and to rule out differential diagnoses of pelvic pain. Patient-reported outcome measures (PROMs) like the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) are valuable instruments for the initial diagnostic assessment and to evaluate treatment response. Classification systems like UPOINTS (urinary, psychosocial, organ specific, infection, neurologic/systemic, tenderness of skeletal muscles, sexual dysfunction) are valuable tools to determine the individual spectrum of symptoms, to guide the adapted diagnostic assessment, and to identify relevant targets for a multimodal and tailored treatment. Close urological monitoring of CP/CPPS patients is usually necessary, especially to minimize the unwarranted use of antibiotics in the case of undulating complaints.

[Urinary diversion for acute epididymitis : Transurethral or suprapubic catheter?] / Harnableitung bei akuter Epididymitis : Transurethraler oder suprapubischer Katheter?

Acute infective epididymitis is the most common cause for scrotal pain in adults. The severe course of the disease requires immediate antimicrobial management, comprised antibiotic treatment and supportive measures. Patients with chronic indwelling catheters and developing epididymitis show a more severe clinical course compared to patients without a catheter. Although it is common clinical practice to place a catheter for the treatment of a systemic infectious condition of the genitourinary tract, there is only limited evidence of support due to the absence of clinical trials.

Linguistic validation and cognitive assessment of the French version of the Acute Cystitis Symptom Score questionnaire.

INTRODUCTION: The Acute Cystitis Symptom Score (ACSS) questionnaire first developed in Russian and Uzbek languages and now available in many other languages can be used for clinical diagnostics and patient-reported outcome (PRO) in female patients with acute uncomplicated cystitis (AUC). The aim of the current study was the linguistic validation and cognitive assessment of the French version of the ACSS questionnaire according to internationally accepted guidelines. METHODS: After two forward translations from Russian into the French language and backward translation into Russian and Uzbek, the two original languages, the scientific committee (SC) performed a slightly adapted French version, which finally was cognitively assessed by female subjects with different ages and educational levels and medical professionals, such as nurses, physicians, and pharmacists. RESULTS: All comments of the female subjects and professionals were discussed within the SC and after slight, but necessary adaptations, the SC agreed on the final study version of the French ACSS. CONCLUSION: Now, the linguistically validated and cognitively assessed French version of the ACSS can be used for clinical studies and practice.

[Complicated urinary tract infections]. / Komplizierte Harnwegsinfektionen.

Urinary tract infections (UTIs) are among the most common bacterial infections in Germany, both in outpatient and inpatient settings. The clinical spectrum is heterogeneous and ranges from benign, often self-limiting, uncomplicated infections to complicated urinary tract infections (cUTIs) with life-threatening courses. Complicated urinary tract infections have a higher risk of chronicity, recurrence and/or progression than uncomplicated infections and may be associated with severe disease progression. Stratification of patients with urinary tract infections is, therefore, of utmost importance. Host factors rather than pathogen attributes determine the pathophysiology and therapy of complicated urinary tract infections and pyelonephritis. Complicated UTIs and pyelonephritis are also associated with high rates of antimicrobial resistance in the causative pathogens, so they should be given particular emphasis.

[Chronic prostatitis/chronic pelvic pain syndrome]. / Chronische Prostatitis/chronisches Beckenschmerzsyndrom.

Chronic prostatitis (CP, or chronic pelvic pain syndrome, CPPS) is defined as chronic pain or discomfort in the pelvic region for at least 3 of the past 6 months, often accompanied by lower urinary tract symptoms, psychosocial impairments and sexual dysfunction. Currently, no biomarkers or clinical test procedures for a definitive diagnosis are available. The main objectives for the diagnostic assessment are to exclude differential diagnoses of pelvic pain and to determine the individual symptom profile of the patient. The UPOINTS classification identifies the individual clinical profile of the patient, provides guidance for the necessary diagnostic steps and is the foundation for a tailored multimodal, symptom-oriented and personalized treatment concept. Regular follow-up controls are needed to monitor the treatment response with the option to modify if necessary.

[Guideline-based treatment of urinary tract infections]. / Leitliniengerechte Therapie von Harnwegsinfektionen.

BACKGROUND: Urinary tract infections (UTIs) are among the most common infections. Especially complicated UTIs have a broad bacterial spectrum, sometimes having high antibiotic resistance rates. The clinical course might be very different and can range from spontaneous cure to fulminant sepsis. OBJECTIVES: Which initial therapy is adequate for which UTI entity and what are the corresponding guidelines recommendations? MATERIALS AND METHODS: This is a review of the current S3 guideline urinary tract infection, the guideline parenteral initial therapy of bacterial infections from the Paul Ehrlich Society, the guideline urological infections from the European Association of Urology (EAU) and the guideline on recurrent uncomplicated UTI in women from the American Urological Association (AUA). RESULTS: Adequate antibiotic therapy is based on the stratification into complicated and uncomplicated, as well as upper and lower infections, and on specific risk factors (e.g., urinary tract catheter) that can be classified according to the ORENUC criteria. Based on this classification, the choice for an empirical antibiotic therapy is made. The spectrum of pathogens should therefore be limited in order to use antibiotics with a narrow spectrum of activity and little collateral damage if possible, thus, preventing both the development of resistance and complications. CONCLUSIONS: Adequate empirical antibiotic therapy and prophylaxis in line with guidelines is based on the clinical classification and risk factors.

[Barriers to guideline adherence : Identification of barriers to guideline adherence using a survey on the AWMF S3 guideline epidemiology, diagnosis, treatment, and management of uncomplicated bacterial, community-acquired urinary tract infections in adult patients]. / Barrieren der Leitlinienadhärenz : Identifizierung von Barrieren der Leitlinienadhärenz am Beispiel einer Umfrage zur AWMF-S3-Leitlinie Epidemiologie, Diagnostik, Therapie und Management unkomplizierter bakterieller ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten.

BACKGROUND: Several studies have shown that nonadherence to guidelines is pretty common in the treatment of urinary tract infections (UTI). However, no urological study has raised the question, what are barriers or reasons for this nonadherence, yet. OBJECTIVES: Consequently, we performed a survey among German urologists with the primary endpoint identification of barriers for nonadherence to German guidelines on UTI. MATERIALS AND METHODS: A 19-item questionnaire was developed and transferred to the online portal "Survey Monkey®" (Private Equity, San Mateo, CA, USA) and tested for usability by our study group. The link for the survey was sent twice to the members of the German Society of Urology (DGU). RESULTS: Overall, 307 questionnaires were completed. The mean age of the study population was 46.7 years (standard deviation 11.5). The majority (34.9%) followed guidelines in 80% of the cases. Main reasons for nonadherence on the physicians' side were 23.4% personal experience and lacking practicality of UTI guidelines on the individual complex patient. On the open questions urologists mostly stated (11.7%) that the main reason on the physician side for nonadherence is ignorance. Therefore they, in open questions, suggest to promote guidelines more in meetings and more designed practically with shortcuts and simple layout. Patient-associated factors mentioned were mostly in 26.7%. Furthermore, German urologists stated that guidelines should also have a patient section, where the main recommendations are explained in plain language. CONCLUSION: We performed the first survey on identifying barriers for nonadherence to guidelines in urology. Despite some limitations, our results are very important for the further design of guidelines. This has the potential to improve guideline adherence.

[Current diagnosis and treatment of sexually transmitted infections]. / Aktuelle Diagnostik und Therapie der sexuell übertragbaren Infektionen.

BACKGROUND: In recent years, there has been an increasing incidence of sexually transmitted infections (STI), which in turn play a major role in urological clinical routine. OBJECTIVES: Which STIs are relevant in urological clinical routine? What kind of recommendations for diagnosis and treatment exist? MATERIALS AND METHODS: Review of evidence-based recommendations from the literature, current guidelines of the European Association of Urology and the Robert-Koch-Institute. RESULTS: STIs can be differentiated into those that cause genital, anal, perianal or oral ulcers from STIs that cause urethritis, cervicitis, or urethral or vaginal discharge. Asymptomatic courses are frequently observed. For diagnosis predominantly amplification methods are recommended. The local resistance situation should be considered. Special attention is paid to the worldwide increasing resistance of gonococci. The sexual partner should also be treated. In addition, diagnosis and therapy of other STIs should be made due to the high rate of co-infection. CONCLUSIONS: Due to the increasing incidence of STIs, the recognition and evidence-based treatment of these infections is essential to avoid ascending infections, long-term consequences, and further transmissions. It is important to assure the infectious material before initiating therapy to be able to switch from the initially initiated calculated therapy (also considering the local resistance situation) to a test-appropriate therapy.

[Urogenital tuberculosis and schistosomiasis (bilharzia) : Urological challenges in displaced persons]. / Urogenitaltuberkulose und Schistosomiasis (Bilharziose) : Urologische Herausforderungen durch Flucht und Vertreibung.

We are observing the largest worldwide wave of migration ever. Displaced persons usually do not have access to general health care and are faced with a lack of hygienic conditions and infection control while fleeing, which leads to an accumulation of "exotic" infectious diseases. The number of patients with tuberculosis (TB) had declined for many years in Germany; however, increasing numbers of cases have recently been observed. For urologists, of course, the manifestations of urogenital TB (UGTB) are of particular interest. Therefore, the basics regarding diagnosis and therapy of UGTB are discussed in this article and explained using case studies. The second important "exotic" infectious disease that urologists are increasingly facing is schistosomiasis. The larvae (found mostly in stagnant water) penetrate through intact human skin, mature and migrate into the liver, from where they immigrate into the venous capillaries of the intestine, the small pelvis, the bladder wall and the distal ureter, and there cause chronic inflammation. All urologists should be familiar with the diagnosis, therapy and prophylaxis of urogenital schistosomiasis and the oncogenesis of schistosomiasis-associated bladder carcinoma.

[Prudent use of antimicrobial prophylaxis : Prevention of increasing antibiotic resistance]. / Sinnvolle Antibiotikaprophylaxe in der Urologie : Vermeidung von zunehmender Resistenzentwicklung.

BACKGROUND: The use of peri-operative antimicrobial prophylaxis during urological procedures to prevent postoperative complications is very common. OBJECTIVES: What kind of recommendations for reasonable use of peri-operative antimicrobial prophylaxis during urological procedures to prevent increasing antibiotic resistance and postoperative complications exist? METHODS: Review of evidence-based recommendations from literature and current Guidelines of the EAU. RESULTS: For urological procedures there are evidenced-based recommendations for using antimicrobial prophylaxis, although the evidence is not always sufficiently high. For endourological procedures it is recommended to use Cephalosporines group 2 (or 3), Aminopenicillin/Beta-lactamase inhibitor or Cotrimoxazole. For transrectal core biopsy of the prostate, depending on the risk, Fluoroquinolones, Cotrimoxazole or targeted prophylaxis are recommended. For laparoscopic or open procedures, partly optional, Cephalosporines group 2 (or 3), Aminopenicillin/Beta-lactamase inhibitor or Cotrimoxazole and for a cystectomy with opening of the intestinal tract Cephalosporines group 2 or an Aminopenicillin/Beta-lactamase inhibitor, together with Metronidazole are recommended. CONCLUSIONS: Using prudent peri-operative antimicrobial prophylaxis patient surgical risk factors as well as the expected spectrum of pathogens and the local resistance profile should be considered. Perioperative antibiotic prophylaxis on the one hand aims at preventing postoperative infections, and on the other hand plays an important role in the total antibiotic consumption. It is therefore a pivotal aspect of "Antimicrobial Stewardship" strategies in the health-care system.

[Epidemiology, diagnostics, therapy, prevention and management of uncomplicated bacterial outpatient acquired urinary tract infections in adult patients : Update 2017 of the interdisciplinary AWMF S3 guideline]. / Epidemiologie, Diagnostik, Therapie, Prävention und Management unkomplizierter, bakterieller, ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten : Aktualisierung 2017 der interdisziplinären AWMF S3­Leitlinie.

BACKGROUND: Update of the 2010 published evidence-based S3 guideline on epidemiology, diagnostics, therapy and management of uncomplicated, bacterial, outpatient-acquired urinary tract infections in adult patients. The guideline contains current evidence for the rational use of antimicrobial substances, avoidance of inappropriate use of certain antibiotic classes and development of resistance. METHODOLOGY: The update was created under the leadership of the German Association of Urology (DGU). A systematic literature search was conducted for the period 01 January 2008 to 31 December 2015. International guidelines have also been taken into account. Evidence level and risk of bias were used for quality review. RESULTS: Updated information on bacterial susceptibility, success, collateral damage and safety of first- and second-line antibiotics was given. For the treatment of uncomplicated cystitis the first line antibiotics are fosfomycin trometamol, nitrofurantoin, nitroxoline, pivmecillinam, trimethoprim (with consideration of the local resistance rates). Fluoroquinolones and cephalosporins should not be used as first choice antibiotics. In the case of uncomplicated pyelonephritis of mild to moderate forms, preferably cefpodoxime, ceftibuten, ciprofloxacin or levofloxacin should be used as oral antibiotics. CONCLUSION: The updated German S3 guideline provides comprehensive evidence- and consensus-based recommendations on epidemiology, diagnostics, therapy, prevention and management of uncomplicated bacterial outpatient acquired urinary tract infections in adult patients. Antibiotic stewardship aspects have significantly influenced the therapeutic recommendations. A broad implementation in all clinical practice settings is necessary to ensure a foresighted antibiotic policy and thus t improve clinical care.

[Testosterone therapy]. / Testosterontherapie.

Hormone replacement therapy with testosterone has become well-established over the course of time. The initial substantial concerns with respect to complications and potential adverse events, particularly in older patients, were proven to be unfounded over time. Testosterone therapy has therefore gradually become a regular treatment modality in urological practice. It has also been shown to represent a valuable tool as supportive treatment for patients with erectile dysfunction and hypogonadism. A variety of testosterone preparations are available for treatment. Recent pharmaceutical developments have greatly improved the practicability and ease of administration for patients. Several guidelines have been developed that provide clearly formulated standards and instructions for indications, contraindications, application, risk factors and monitoring of testosterone therapy. Adverse events affecting the cardiovascular system and especially diseases of the prostate gland are of great importance, thus making the urologist the primary partner in the treatment of patients with testosterone deficiency.

[Urosepsis. Update on diagnosis and treatment]. / Urosepsis. Aktuelles zu Diagnostik und Therapie.

BACKGROUND: Sepsis is an acute systemic response to the presence of bacteria and bacterial components in the macroorganism, and urosepsis is defined as sepsis caused by an infection in the urogenital tract. The urogenital tract is considered to be responsible for about 30 % of the cases of septic processes, whereby obstructive uropathy is causative in about 80 % of these cases. Sepsis manifests as an initially predominant proinflammatory response by widespread release of inflammatory mediators as a result of activation of cells responsive to infectious components such as bacterial toxins, which is then accompanied by a counter-regulatory anti-inflammatory response. DIAGNOSIS AND THERAPY: Prior to antibiotic therapy, blood and urine cultures are recommended, while procalcitonin and lactate can be considered diagnostically relevant biomarkers. Furthermore, early imaging to localize the level of obstruction and infectious focus should be carried out. Treatment is divided into causal therapy (antimicrobial therapy and infectious source), supportive therapy (fluids and oxygen administration), and adjunctive therapy (sepsis-specific therapy).

[Urinary tract infections in the elderly]. / Harnwegsinfektionen im Alter.

Urinary tract infections (UTIs) and asymptomatic bacteriuria are frequent in elderly patients. Distinguishing UTI from asymptomatic bacteriuria in older adults, particularly those living in long-term care facilities, might be a challenge for physicians due to the presence of confounding factors, such as an overactive bladder, prostate enlargement, and an indwelling bladder catheter. The absence of standards in the definition and treatment of UTI in the elderly frequently leads to overtreatment. Consequently, antibiotic selection pressure increases and as a result multidrug-resistant organisms might arise. On the other hand, insufficient treatment can result in prolonged and complicated courses of infections or increased morbidity. This review covers the definition, prevalence, diagnosis and management of UTI in older adults.

[Antibiotic resistance and their significance in urogenital infections: new aspects]. / Antibiotikaresistenz und deren Bedeutung bei urogenitalen Infektionen : Neue Aspekte.

Urinary tract infections (UTI) are among the most frequent bacterial infections and therefore make a significant contribution to the widespread use and extensive misuse of antibacterial drugs. The amount of antibiotics used directly correlates with the emergence of antibiotic resistance. The World Health Organization (WHO) has recently issued a fact sheet highlighting the worldwide increase in antibiotic resistance. The spectrum of urological diseases affected by antibiotic resistance ranges from benign uncomplicated cystitis to severe life-threatening urosepsis and from urethritis to multidrug resistant tuberculosis. The European Section of Infections in Urology (ESIU) performs an annual surveillance study to evaluate antibiotic resistance in urology which revealed excessively high resistance rates, similar to other surveillance studies. In the light of these developments the World Alliance against Antibiotic Resistance (WAAAR) has advocated a 10-point action plan to combat the rapid rise of worldwide antibiotic resistance.

[Urinary tract infections]. / Harnwegsinfektionen.

Urinary tract infections (UTI) are amongst the most frequent bacterial infections and therefore responsible for a great amount of antibiotic administration. UTI may present as benign, uncomplicated cystitis or severe, life-threatening urosepsis. Due to the heterogeneity of UTI the European Section of Infections in Urology (ESIU) has introduced a phenotypical classification, based upon the clinical presentation, the risk factors and the antibiotic susceptibility of the causative pathogens. Antibiotic treatment of the UTI varies accordingly. In uncomplicated cystitis antibiotics with low potential for collateral damage are recommended, which are mainly indicated for these infections. In uncomplicated pyelonephritis fluoroquinolones and 3rd generation cephalosporines are recommended. Antibiotic treatment regimens of complicated UTI depend very much on the antibiotic susceptibility according to regional resistance statistics. In urosepsis an early diagnosis and therapy is mandatory. In this regard a procalcitonin level > 0.25 µg/l has a good sensitivity and acceptable specificity in predicting bacteremia. Apart from the early antibiotic therapy successful decompression of the obstructed urinary tract is a predictor of survival. In children UTI are also amongst the most important bacterial infections, although symptoms are frequently not characteristic. The correct sampling of urine for microbiological investigations is critical. Due to the increasing fluoroquinolone resistance, infectious complications after transrectal prostate biopsy are becoming more frequent. Strategies to decrease complications encompass, amongst others, microbiological screening of the faecal flora for fluoroquinolone resistance, administration of alternative antibiotics for prophylaxis and alternative techniques for biopsy, such as perineal prostate biopsy.

[Biopsies of the kidney, prostate and urinary bladder]. / Biopsie der Prostata und Punktion der Niere und Blase.

BACKGROUND: Biopsies of the kidney, prostate and urinary bladder are amongst the most frequent interventions in urology. A correct indication, preparation and performance are important to achieve good results and low complication rates. OBJECTIVES: In this review complication management in biopsies of the kidney, prostate and urinary bladder are discussed. MATERIALS AND METHODS: A selective search of the literature, with emphasis on systematic reviews and larger cohort studies was performed. RESULTS: Complication rates are generally low. However, certain factors such as coagulation disorders, anatomical malformations, accompanying morbidities or antibiotic resistance may play a significant role and increase rates of complications. Especially complications such as hematuria and injury of contiguous organs are described in the literature. DISCUSSION: Biopsies of the kidney, prostate and urinary bladder can be performed with low complication rates if general and specific factors in the planning of the intervention and prevention of complications are considered.

[Auricular acupuncture in patients with detrusor overactivity: a pilot study]. / Ohrakupunktur bei Detrusorhyperaktivität : Eine Pilotstudie.

BACKGROUND: Patients suffering from overactive bladder/detrusor overactivity (OAB/DO) seem to benefit from body acupuncture. The study was carried out to test if auricular acupuncture (AAP), which is supposed to show an immediate effect, can also cause urodynamic changes. PATIENTS AND METHODS: The OAB/DO condition was verified by means of cystometry in 14 patients. These patients were subjected to bilateral AAP after cystometry, a second cystometry was performed 20-30 min later and data were analyzed using the Wilcoxon rank-sum test. RESULTS: None of the patients showed local or systemic complications but DO persisted in all patients and urge urinary incontinence (UUI) persisted in 85 % (11/13) of patients. Intravesical pressure decreased after AAP but without reaching statistical significance. In 22 % (2/9) of patients residual volume (RV) disappeared completely while 78 % (7/9) of patients showed significant reduction of RV. CONCLUSIONS: This study could not prove a significant influence of AAP on DO or UUI; therefore an immediate effect of AAP in patients suffering from OAB/DO seems to be unlikely. Further studies are necessary to evaluate the effect of repeated AAP sessions on urodynamic changes.

Perineal body repair in patients with third degree rectocele: a critical analysis of the tissue fixation system.

AIM: We describe the technique of tissue fixation system (TFS) perineal body repair in patients presenting with symptomatic third degree rectocele. METHOD: The single sling TFS perineal body repair is performed in three surgical steps: (i) dissection of the rectum off the vagina and laterally displaced perineal body; (ii) identification of the deep transverse perineii muscles beyond their insertion point behind the descending pubic ramus; (iii) elevation and approximation of the separated and laterally displaced perineal bodies by insertion, without tension, of non-stretch 7 mm polypropylene tape into the bodies of the deep transverse perineii muscles. RESULTS: From January 2007 to December 2009 we performed the TFS operation for 30 women, median age 61 (range 47-87) years, mean parity 2.6 (range 1-5), with third degree symptomatic low rectocele (median obstructive defaecation syndrome score 19; range 11-24). Median hospital stay was 24 (range 12-96) h. The median visual analogue scale for postoperative pain was 1 (range 1-7). Complications occurred in three cases (10%) and included a surfaced tape that was partly resected (repair maintained), a recurrence of the rectocele due to incorrect placement (failed repair) and a foreign body abscess requiring tape removal. At 12-month follow-up, 27 patients (90%) reported normal defaecation and the median obstructive defaecation syndrome score was significantly reduced to 4 (range 1-6; P < 0.001). CONCLUSION: The TFS perineal body repair is an effective, safe, minimally invasive treatment in women with symptomatic low rectocele.

Influence of infection on the distribution patterns of NIH-Chronic Prostatitis Symptom Index scores in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex condition for which the etiological determinants are still poorly defined. To better characterize the diagnostic and therapeutic profile of patients, an algorithm known as UPOINT was created, addressing six major phenotypic domains of CP/CPPS, specifically the urinary (U), psycho-social (P), organ-specific (O), infection (I), neurological/systemic (N) and muscular tenderness (T) domains. An additional sexual dysfunction domain may be included in the UPOINT(S) system. The impact of the infection domain on the severity of CP/CPPS symptoms is a controversial issue, due to the contradictory results of different trials. The aim of the present retrospective study was to further analyze the extent to which a positive infection domain of UPOINTS may modify the pattern of CP/CPPS symptom scores, assessed with the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). In a cohort of 935 patients that was divided on the basis of the presence or absence of prostatic infection, more severe clinical symptoms were shown by the patients with infection (median NIH total score: 24 versus 20 points in uninfected patients; P<0.001). Moreover, NIH-CPSI score distribution curves were shifted towards more severe symptoms in patients with a positive infection domain. Division of the patients into the six most prominent phenotypic clusters of UPOINTS revealed that the 'prostate infection-related sexual dysfunction' cluster, including the highest proportion of patients with evidence of infection (80%), scored the highest number of NIH-CPSI points among all the clusters. To assess the influence of the infection domain on the severity of patients' symptoms, all subjects with evidence of infection were withdrawn from the 'prostate infection-related sexual dysfunction' cluster. This modified cluster showed symptom scores significantly less severe than the original cluster, and the CPSI values became comparable to the scores of the five other clusters, which were virtually devoid of patients with evidence of infection. These results suggest that the presence of pathogens in the prostate gland may significantly affect the clinical presentation of patients affected by CP/CPPS, and that the infection domain may be a determinant of the severity of CP/CPPS symptoms in clusters of patients phenotyped with the UPOINTS system. This evidence may convey considerable therapeutic implications.