Hirocidins, Cytotoxic Metabolites from Streptomyces hiroshimensis, Induce Mitochondrion-mediated Apoptosis.

Recent advances in whole genome sequencing have revealed an immense microbial potential for the production of therapeutic small molecules, even from well-known producers. To access this potential, we subjected prominent antimicrobial producers to alternative antiproliferative assays using persistent cancer cell lines. Described herein is our discovery of hirocidins, novel secondary metabolites from Streptomyces hiroshimensis with antiproliferative activities against colon and persistent breast cancer cells. Hirocidin A is an unusual nine-membered carbocyclic maleimide and hirocidins B and C are relatives with an unprecedented, bridged azamacrocyclic backbone. Mode of action studies show that hirocidins trigger mitochondrion-dependent apoptosis by inducing expression of the key apoptotic effector caspase-9. The discovery of new cytotoxins contributes to scaffold diversification in anticancer drug discovery and the reported modes of action and concise total synthetic route for variant A set the stage for unraveling specific targets and biochemical interactions of the hirocidins.

Genome mining for new enediyne antibiotics.

Enediyne antibiotics epitomize nature's chemical creativity. They contain intricate molecular architectures that are coupled with potent biological activities involving double-stranded DNA scission. The recent explosion in microbial genome sequences has revealed a large reservoir of novel enediynes. However, while hundreds of enediyne biosynthetic gene clusters (BGCs) can be detected, less than two dozen natural products have been characterized to date as many clusters remain silent or sparingly expressed under standard laboratory growth conditions. This review focuses on four distinct strategies, which have recently enabled discoveries of novel enediynes: phenotypic screening from rare sources, biosynthetic manipulation, genomic signature-based PCR screening, and DNA-cleavage assays coupled with activation of silent BGCs via high-throughput elicitor screening. With an abundance of enediyne BGCs and emerging approaches for accessing them, new enediyne natural products and further insights into their biogenesis are imminent.

N-Cα Bond Cleavage Catalyzed by a Multinuclear Iron Oxygenase from a Divergent Methanobactin-like RiPP Gene Cluster.

DUF692 multinuclear iron oxygenases (MNIOs) are an emerging family of tailoring enzymes involved in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs). Three members, MbnB, TglH, and ChrH, have been characterized to date and shown to catalyze unusual and complex transformations. Using a co-occurrence-based bioinformatic search strategy, we recently generated a sequence similarity network of MNIO-RiPP operons that encode one or more MNIOs adjacent to a transporter. The network revealed >1000 unique gene clusters, evidence of an unexplored biosynthetic landscape. Herein, we assess an MNIO-RiPP cluster from this network that is encoded in Proteobacteria and Actinobacteria. The cluster, which we have termed mov (for methanobactin-like operon in Vibrio), encodes a 23-residue precursor peptide, two MNIOs, a RiPP recognition element, and a transporter. Using both in vivo and in vitro methods, we show that one MNIO, homologous to MbnB, installs an oxazolone-thioamide at a Thr-Cys dyad in the precursor. Subsequently, the second MNIO catalyzes N-Cα bond cleavage of the penultimate Asn to generate a C-terminally amidated peptide. This transformation expands the reaction scope of the enzyme family, marks the first example of an MNIO-catalyzed modification that does not involve Cys, and sets the stage for future exploration of other MNIO-RiPPs.

Maternity Leave Satisfaction Among Physicians Compared with Nonphysician Professionals.

Objective: The objective of this study was to compare maternity leave satisfaction between physicians and nonphysicians. Currently, paid maternal leave is not guaranteed in the United States, resulting in palpable dissatisfaction among parents. Previous studies have shown associations between length of paid leave and career satisfaction and maternal happiness. Materials and Methods: A Qualtrics® electronic survey was distributed to female professionals through email and social media from April 2019 to March 2020. Inclusion criterion was ≥1 child by birth or adoption, or active pregnancy. Continuous and categorical data were analyzed using two-sample t-test and chi-square, respectively. Results: Of 808 respondents, 77% were physicians. Mean age at birth/adoption of first child was higher in physicians versus nonphysicians (32.1 years vs. 29.7 years; p < 0.001). Physicians took shorter maternity leave than nonphysicians (10.9 weeks vs. 12.0 weeks, p = 0.017) with half of that time paid by employers (5.4 weeks vs. 5.9 weeks, p = 0.2). Dissatisfaction was high among physicians (85.1%) and nonphysicians (92.4%) that correlates with maternity leave compensation dissatisfaction (49% vs. 71.3%, p < 0.001). Thirty-four percent of physicians versus 41% of nonphysicians stated that their health was negatively impacted by maternity leave length. Physicians and nonphysicians reported similar incidences of depression, and breastfeeding, delivery, and other postpartum complications. When queried, 38.8% of physicians and 57% of nonphysicians said they would desire >16 weeks of paid maternity leave (p < 0.001). Conclusions: In conclusion, dissatisfaction among professional women on maternity leave duration and compensation is high in the United States. Given health implications for both mother and child, this should invite further discussion and changes.

Targeted Discovery of Cryptic Enediyne Natural Products via FRET-Coupled High-Throughput Elicitor Screening.

Enediyne antibiotics are a striking family of DNA-cleaving natural products with high degrees of cytotoxicity and structural complexity. Microbial genome sequences, which have recently accumulated, point to an untapped trove of "cryptic" enediynes. Most of the cognate biosynthetic gene clusters (BGCs) are sparingly expressed under standard growth conditions, making it difficult to characterize their products. Herein, we report a fluorescence-based DNA cleavage assay coupled with high-throughput elicitor screening for the rapid, targeted discovery of cryptic enediyne metabolites. We applied the approach to Streptomyces clavuligerus, which harbors two such BGCs with unknown products, identified steroids as effective elicitors, and characterized 10 cryptic enediyne-derived natural products, termed clavulynes A-J with unusual carbonate and terminal olefin functionalities, with one of these congeners matching the recently reported jejucarboside. Our results contribute to the growing repertoire of enediynes and provide a blueprint for identifying additional ones in the future.

Targeted Discovery of Cryptic Metabolites with Antiproliferative Activity.

Microorganisms have provided a rich source of therapeutically valuable natural products. Recent advances in whole genome sequencing and bioinformatics have revealed immense untapped potential for new natural products in the form of silent or "cryptic" biosynthetic genes. We herein conducted high-throughput elicitor screening (HiTES) in conjunction with cytotoxicity assays against selected cancer cell lines with the goal of uncovering otherwise undetectable cryptic metabolites with antiproliferative activity. Application to Streptomyces clavuligerus facilitated identification of clavamates A and B, two bioactive metabolites with unusual structural features, as well as facile activation of a gene cluster coding for tunicamycin, which exhibited strong growth-inhibitory activity. The elicitor we identified was pleiotropic, additionally leading to the discovery of a modified, bicyclic pentapeptide natural product. Our results highlight the utility of this approach in identifying new molecules with antiproliferative activity from even overexploited microbial strains.

Momomycin, an Antiproliferative Cryptic Metabolite from the Oxytetracycline Producer Streptomyces rimosus.

Natural products provide an important source of pharmaceuticals and chemical tools. Traditionally, assessment of unexplored microbial phyla has led to new natural products. However, with every new microbe, the number of orphan biosynthetic gene clusters (BGC) grows. As such, the more difficult proposition is finding new molecules from well-studied strains. Herein, we targeted Streptomyces rimosus, the widely-used oxytetracycline producer, for the discovery of new natural products. Using MALDI-MS-guided high-throughput elicitor screening (HiTES), we mapped the global secondary metabolome of S. rimosus and structurally characterized products of three cryptic BGCs, including momomycin, an unusual cyclic peptide natural product with backbone modifications and several non-canonical amino acids. We elucidated important aspects of its biosynthesis and evaluated its bioactivity. Our studies showcase HiTES as an effective approach for unearthing new chemical matter from "drained" strains.

Structural Elucidation of Cryptic Algaecides in Marine Algal-Bacterial Symbioses by NMR Spectroscopy and MicroED.

Microbial secondary metabolite discovery is often conducted in pure monocultures. In a natural setting, however, where metabolites are constantly exchanged, biosynthetic precursors are likely provided by symbionts or hosts. In the current work, we report eight novel and architecturally unusual secondary metabolites synthesized by the bacterial symbiont Phaeobacter inhibens from precursors that, in a native context, would be provided by their algal hosts. Three of these were produced at low titres and their structures were determined de novo using the emerging microcrystal electron diffraction method. Some of the new metabolites exhibited potent algaecidal activity suggesting that the bacterial symbiont can convert algal precursors, tryptophan and sinapic acid, into complex cytotoxins. Our results have important implications for the parasitic phase of algal-bacterial symbiotic interactions.

Robotic Surgery: Advancements and Inflection Points in the Field of Gynecology.

Robotics has become an essential part of the surgical armamentarium for a growing number of surgeons around the world. New companies seek to compete with established robotic systems that have dominated the market to date. Evolving robotic surgery platforms have introduced technologic and design advancements to optimize ergonomics, improve visualization, provide haptic feedback, and make systems smaller and cheaper. With the introduction of any new technology in the operating room, it is imperative that safeguards be in place to ensure its appropriate use. Current processes for granting of hospital robotic surgery privileges are inadequate and must be strengthened and standardized.

Surgical site infections in gynecology: the latest evidence for prevention and management.

PURPOSE OF REVIEW: Surgical site infection (SSI) remains one of the most common postoperative surgical complications. Prevention and appropriate treatment remain paramount. RECENT FINDINGS: Evidence-based recommendations include recognition and reduction of preoperative risks including hyperglycemia and smoking, treatment of preexisting infections, skin preparation with chlorhexidine gluconate, proper use of preoperative antibiotics, and implementation of prevention bundles. Consideration should be given to the use of dual antibiotic preoperative treatment with cephazolin and metronidazole for all hysterectomies. SUMMARY: Despite advancements, SSI in gynecologic surgery remains a major cause of perioperative morbidity and healthcare cost. Modifiable risk factors should be evaluated and patients optimized to the best extent possible prior to surgery. Preoperative risks include obesity, hyperglycemia, smoking, and untreated preexisting infections. Intraoperative risk-reducing strategies include appropriate perioperative antibiotics, correct topical preparation, maintaining normothermia, and minimizing blood loss. Additionally, early recognition and prompt treatment of SSI remain crucial.

A Systematic Review of Validity Evidence for the Fundamentals of Laparoscopic Surgery Examination in Gynecology.

OBJECTIVE: The Fundamentals in Laparoscopic Surgery (FLS) examination is designed to test laparoscopic surgery skills. Our aim for this systematic review was to examine validity evidence supporting or refuting the FLS examination specifically as a high-stakes summative assessment tool in gynecology. DATA SOURCES: The data sources were PubMed, MEDLINE, Embase, and Scopus. METHODS OF STUDY SELECTION: The study eligibility criterion was the subject of the FLS examination as an assessment tool in gynecology. We developed a data extraction tool and assigned articles for screening and extraction to all authors, who then abstracted data independently. Conflicts that arose during the extraction process were resolved by consensus. We organized validity evidence for the cognitive and manual skills portions on the basis of the categories of current validation standards. TABULATION, INTEGRATION, AND RESULTS: From 1971 citations identified, 9 studies were included, involving 319 participants. For the cognitive portion of the test, the results were mixed in 5 studies in relationships with the other variables category. For the manual portion of the test, most of the studies focused on the relationships with other variables evidence with mixed findings. The concerning findings in the manual skills portion included the lack of transferability of skills to the operating room, limited mixed evidence for improvement in operating room performance, and worse performance by obstetrics and gynecology surgeons compared with other specialties. We did not find supportive content-based, response process, or consequential evidence in either the cognitive or manual skills portion of the test. CONCLUSION: Validity evidence for the FLS examination was either mixed, as it pertained to relationships with other variables, or lacking in other important evidence categories. Further evidence is required to justify the use of the FLS examination scores as a high-stakes summative assessment.

Placement of mid-urethral mesh slings at the time of vaginal prolapse repair does not affect post-operative sexual function or orgasm.

INTRODUCTION AND HYPOTHESIS: Because of the relationship between the clitoral neurovascular supply and the urethra, the dissection for placement of mid-urethral slings (MUS) may negatively impact orgasmic function. We aimed to analyze the role of MUS in orgasmic and overall sexual function in patients undergoing prolapse surgery. METHODS: A single institution retrospective review was performed on 157 patients undergoing prolapse surgery with and without MUS from 2008 to 2014. Pelvic Organ Prolapse Incontinence Sexual Questionnaires (PISQ-12) scores at baseline, 6, and 12 months post-operatively were compared. The difference in overall mean post-operative PISQ-12 scores at 6 and 12 months in those undergoing POP with or without MUS placement was assessed using Wilcoxon rank tests. RESULTS: Of 157 women who underwent prolapse surgery, 81 (52%) had concomitant MUS. Mean baseline PISQ-12 scores were 32 in both groups (p = 0.98). Post-operative PISQ-12 scores between the two groups did not differ at 6 (p = 0.96) or 12 months (p = 0.65). Within the MUS group, mean overall PISQ-12 scores improved at 6 (p = 0.05) and 12 months (p < 0.01). Mean overall PISQ-12 scores did not improve in patients who did not have slings placed at 6 (p = 0.10) or 12 months (p = 0.15). Orgasm frequency and intensity did not differ between the two groups at 6 (p = 0.39, p = 0.91, respectively) or 12 months (p = 0.11, p = 0.44, respectively). CONCLUSION: MUS at the time of prolapse repair did not affect orgasmic or overall sexual function. PISQ-12 scores improved after prolapse surgery with concomitant MUS placement. Our findings may help counsel patients regarding the risk of MUS placement affecting sexual function.

Symptom and Quality of Life Improvements After Pelvic Floor Physical Therapy in a Clinical Population of Women With Pelvic Pain and Other Symptoms.

OBJECTIVES: This study aimed to evaluate changes in validated symptom scores at intake and discharge in women undergoing pelvic floor physical therapy (PFPT) for pain and other pelvic floor symptoms. METHODS: Consecutive women starting PFPT during 1 year were reviewed. History, demographics, and Pelvic Floor Distress Inventory Questionnaire - Short Form 20 (PFDI) total and domain scores (Pelvic Organ Prolapse Distress Inventory-6, Urogenital Distress Inventory-6, Colorectal-Anal Distress Inventory-8), Pelvic Floor Impact Questionnaire (PFIQ-7), and pain levels on a numeric rating scale (NRS) were collected at intake and discharge. Data were analyzed with descriptive statistics and sign tests. RESULTS: Of 474 women, mean age was 50.3 ± 16.7 years (range, 18-87 years) and the most common indication for PFPT was pelvic pain (208/474; 43.9%). In women with complete data, pretreatment to posttreatment median scores improved on the PFDI (77.3 vs 41.8; P < 0.0001), Urogenital Distress Inventory (37.5 vs 16.0; P < 0.0001), and PFIQ (58.0 vs 19.0; P < 0.0001), and the minimal clinically important difference was met for the PFDI, PFIQ, and Colorectal-Anal Distress Inventory. Women with primarily pelvic pain (n = 208) achieved significant improvements in PFDI, PFIQ, and NRS scores (P < 0.0001 for all) as well as the minimal clinically important difference for these measures. Pain patients with a history of pelvic surgery (n = 50) also had significant improvements in PFIQ and NRS but not PFDI scores. CONCLUSIONS: Most women referred to PFPT demonstrated symptom improvements as measured by validated instruments.

Small Fiber Polyneuropathy in Hunner Lesion and Non-Hunner Lesion Interstitial Cystitis/Bladder Pain Syndrome.

OBJECTIVE: This study aimed to determine whether small fiber polyneuropathy (SFPN) diagnosis differs between Hunner lesion interstitial cystitis/bladder pain syndrome (HL IC/BPS) and non-Hunner lesion IC/BPS (NHL IC/BPS). METHODS: This was a pilot study of 20 women with IC/BPS. Results from baseline questionnaires, such as Genitourinary Pain Index, Interstitial Cystitis Symptom Index/Interstitial Cystitis Problem Index (ICSI/ICPI), Patient Health Questionnaire-2, were collected.Two punch biopsies were performed on each patient: distal leg and thigh. The samples were evaluated for intraepidermal nerve fiber density. One intraepidermal nerve fiber density less than the fifth percentile, regardless of site, indicated a positive SPFN diagnosis. RESULTS: Twenty patients were enrolled; 10 HL IC/BPS and 10 NHL IC/BPS. The HL IC/BPS group was found to be significantly older than the NHL IC/BPS group (63 vs 48 years, P = 0.007). No significant differences were found in employment or relationship statuses, or in levels of education or comorbidities between the 2 groups.Sixty percent (6/10) of patients had SFPN in the NHL IC/BPS group compared with 40% (4/10) in the HL IC/BPS group. No significant differences were seen in SFPN positivity (P = 0.3) or Genitourinary Pain Index, Patient Health Questionnaire-2, or Interstitial Cystitis Symptom Index/Interstitial Cystitis Problem Index scores between the NHL and HL IC/BPS groups. CONCLUSIONS: Similar to previously published studies, 60% of NHL IC/BPS patients in this cohort were positive for SFPN compared with only 40% of the HL IC/BPS patients. Larger studies may be needed to realize the full impact of SFPN in IC/BPS.

Where Have All the Emergencies Gone? The Impact of the COVID-19 Pandemic on Obstetric and Gynecologic Procedures and Consults at a New York City Hospital.

STUDY OBJECTIVE: The purpose of this study was to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on surgical volume and emergency department (ED) consults across obstetrics-gynecology (OB-GYN) services at a New York City hospital. DESIGN: Retrospective cohort study. SETTING: Tertiary care academic medical center in New York City. PATIENTS: Women undergoing OB-GYN ED consults or surgeries between February 1, 2020 and April 15, 2020. INTERVENTIONS: March 16 institutional moratorium on elective surgeries. MEASUREMENTS AND MAIN RESULTS: The volume and types of surgeries and ED consults were compared before and after the COVID-19 moratorium. During the pandemic, the average weekly volume of ED consults and gynecology (GYN) surgeries decreased, whereas obstetric (OB) surgeries remained stable. The proportions of OB-GYN ED consults, GYN surgeries, and OB surgeries relative to all ED consults, all surgeries, and all labor and delivery patients were 1.87%, 13.8%, 54.6% in the pre-COVID-19 time frame (February 1-March 15) vs 1.53%, 21.3%, 79.7% in the COVID-19 time frame (March 16-April 15), representing no significant difference in proportions of OB-GYN ED consults (p = .464) and GYN surgeries (p = .310) before and during COVID-19, with a proportionate increase in OB surgeries (p <.002). The distribution of GYN surgical case types changed significantly during the pandemic with higher proportions of emergent surgeries for ectopic pregnancies, miscarriages, and concern for cancer (p <.001). Alternatively, the OB surgery distribution of case types remained relatively constant. CONCLUSION: This study highlights how the pandemic has affected the ways that patients in OB-GYN access and receive care. Institutional policies suspending elective surgeries during the pandemic decreased GYN surgical volume and affected the types of cases performed. This decrease was not appreciated for OB surgical volume, reflecting the nonelective and time-sensitive nature of obstetric care. A decrease in ED consults was noted during the pandemic begging the question "Where have all the emergencies gone?" Although the moratorium on elective procedures was necessary, "elective" GYN surgeries remain medically indicated to address symptoms such as pain and bleeding and to prevent serious medical sequelae such as severe anemia requiring transfusion. As we continue to battle COVID-19, we must not lose sight of those patients whose care has been deferred.

Deprescribing long-term opioid therapy in patients with chronic pain.

Proposed regulatory changes will limit the access to opioids by Australian patients with chronic pain, many of whom are under the care of consultant physicians. This review summarises points of consensus on opioid deprescribing that emerged from the interaction of an expert panel and the audience at a symposium on the topic held in Sydney in 2019. Each of these consensus points speaks to the need for an individualised, patient-centred approach. In other words, 'treat the patient, not the pill count'.

Comparing Surgical Experience and Skill Using a High-Fidelity, Total Laparoscopic Hysterectomy Model.

OBJECTIVE: To evaluate differences in standardized scores and surgical confidence in the completion of a standardized total laparoscopic hysterectomy and bilateral salpingo-oophorectomy (TLH-BSO) among obstetrician-gynecologists (ob-gyns) with different levels of training, and to assess a TLH-BSO model for validity. METHODS: We conducted a prospective cohort study of 68 participants within four categories of ob-gyns: 1) graduating or recently graduated residents (n=18), 2) minimally invasive gynecologic surgery graduating or recently graduated fellows (n=16), 3) specialists in general obstetrics and gynecology (n=15), and 4) fellowship-trained minimally invasive gynecologic surgery subspecialists (n=19) who completed a TLH-BSO simulation. Participants completed presimulation questionnaires assessing laparoscopic confidence. Participants performed a video-recorded TLH-BSO and contained specimen removal on a standardized 250-g biological model in a simulated operating room and completed a postsimulation questionnaire. RESULTS: Randomized videos were scored by blinded experts using the validated OSATS (Objective Structured Assessment of Technical Skills). The surgery was divided into five standardized segments: 1) adnexa, 2) dissection and pedicles, 3) colpotomy, 4) cuff closure, and 5) tissue extraction. Minimally invasive gynecologic surgery subspecialists averaging 8.9 years in practice scored highest in all categories (overall median score 91%, P<.001), followed by fellows (64%, P<.001), specialists in obstetrics and gynecology averaging 19.7 years in practice (63%, P<.001), and residents (56%, P<.001). Residents, fellows and specialists in obstetrics and gynecology were comparable overall. Fellows scored higher on cuff closure (63% vs 50%, P<.03) and tissue extraction (77% vs 60%, P<.009) compared with specialists in obstetrics and gynecology. Minimally invasive gynecologic surgery subspecialists were fastest overall and on each individual component. Residents were slowest in almost all categories. CONCLUSION: When performing a TLH-BSO of a standardized 250-g uterus on a simulation model, fellowship-trained minimally invasive gynecologic surgery subspecialists achieved higher OSATS in all areas and completed all components faster. Similar performances were noted between residents, fellows, and specialists in obstetrics and gynecology in practice an average of 19.7 years. FUNDING SOURCE: Support from Applied Medical, Medtronic, CooperSurgical, and Karl Storz in the form of in-kind equipment was obtained through unrestricted educational grants.

A Novel Approach to Managing Post Retropubic Vaginal Sling Pain.

OBJECTIVE: To describe a novel technique of using peripheral nerve neuromodulation (PNNM) for the treatment of refractory, mesh-induced chronic pelvic pain. Chronic pelvic pain associated with mesh can be a debilitating complication and there is currently no consensus on treatment. PNNM has been shown to be successful in the treatment of post-traumatic neuralgias but has yet to be studied in mesh complications. MATERIALS AND METHODS: We present a case of a 50-year-old woman who had unrelenting pelvic pain after retropubic sling placement. She failed multiple therapies including medications, mesh removal, pelvic floor physical therapy, pudendal neuromodulation, and pelvic floor onabotulinumtoxinA trigger point injections. RESULTS: The only treatment that provided temporary relief of this patient's pain was transvaginal trigger point injections along with a right pudendal nerve block using 40 mg triamcinolone and 0.5% ropivacaine. To help define if treatment at the site of her pain would provide relief, a series of blocks were done by advancing a needle retropubically to her area of pain and injecting triamcinolone and 0.5% ropivacaine. This injection, which corresponded to the previous tract of her retropubic sling, provided temporary, but profound, relief. PNNM was then done with placement of the electrode in the retropubic space at the site of her pain. This provided instantaneous relief of almost all of her pain symptoms. Twelve months postoperatively, the patient continued to have >90% improvement in her pain. CONCLUSION: Focused PNNM is a simple procedure and can provide symptomatic relief for refractory postvaginal mesh pain.

The clinical rate of antibiotic change following empiric treatment for suspected urinary tract infections.

PURPOSE: To determine the rate of antibiotic change in an outpatient setting following empiric treatment of culture proven UTI and to identify risk factors associated with change. METHODS: Patients with suspected UTI and urine culture were reviewed (January 2016-June 2016). Those with a positive culture were categorized by whether or not they were treated empirically. Empiric treatment was evaluated for associations with clinical-demographic data, symptoms and urinalysis (UA). Antibiotic change was evaluated with clinical-demographic data, urine culture, and resistance patterns. RESULTS: 916 urine cultures (636 patients) were included. 391 (43%) cultures were positive, and 164 (42%) were treated empirically. Clinical-demographic data did not differ between groups. Those treated empirically had more documented UTI symptoms (93 vs 58%, P < 0.001), and UA abnormalities including positive nitrites (51 vs 29%, P < 0.001), 3 + leukocyte esterase (27 vs 19%, P = 0.002) and 3 + blood (13 vs 4%, P = 0.005). Of those treated empirically, 42/164 (26%) required an antibiotic change, and this was associated with immunosuppression (12 vs 2%, P = 0.027) resistance to > 3 antibiotics (33 vs 20%, P = 0.039) and also resistance to fluoroquinolone (50 vs 30%, P = 0.016), monobactam (19 vs 7% P = 0.042) and TMP-SMX (52 vs 19%, P < 0.001). CONCLUSIONS: Almost one-quarter of patients treated empirically required antibiotic change. This was driven largely by bacterial resistance. New technologies allowing rapid bacterial identification and sensitivity may improve patient care.

Peyronie's Disease is common in poorly controlled diabetics but is not associated with the Metabolic Syndrome.

PURPOSE: The purpose of the study is to investigate if metabolic syndrome (MS) and other comorbidities are associated with Peyronie's disease (PD). METHODS: A total of 1833 patients retrospectively investigated and divided into two groups: Group A - PD patients (n = 319) and Group B - non-PD patients (n = 1303). The two groups were fully evaluated for diabetes mellitus (DM) with the glycated hemoglobin (HbA1c), hypertension (HTN), dyslipidemia (DL), obesity by measuring body mass index, total testosterone (T), penile vascular circulation measuring Peak systolic velocity (PSV) as indicator of arterial supply, end-diastolic velocity (EDV) as indicator of venous output, and finally, smoking. RESULTS: The presence of diabetes was significantly correlated with PD (P = 0.005). Patients with diabetes had a 7% higher incidence of PD. However, patients with the highest HbA1c level of >8.5 had an increased odds ratio of 1.6 (P = 0.025, confidence interval [CI] =1.061-2.459) of having PD. Increased age was significantly correlated with PD (P = 0.025). For each year of life, the likelihood of having PD increases by an odds ratio of 1.019, or 2% per year (P = 0.001, CI = 1.004-1.027). Unexpectedly, DL (P = 0.006) and smoking (P = 0.041) were associated with lower incidences of PD. Patients with DL or smoking had a 5%-7% lower incidence of PD with an odds ratio of 0.6 (P = 0.006, CI = 0.410-0.864). HTN (P = 0.621) and the total number of comorbidities (P = 0.436) were not correlated with PD. Mean serum T values were statistically (P = 0.43) but not clinically significant among patients with Peyronie's versus patients without Peyronie's (4.62 vs. 4.38 ng/ml). Neither low PSV (Fisher's exact test P = 0.912) nor abnormal EDV (Fisher's exact test P = 0.775) was correlated with the finding of PD. CONCLUSIONS: While MS was not associated with PD, diabetes, particularly poorly controlled diabetes, was associated with an increased rate. Further research into the interaction of PD and metabolic disease is warranted.