The impact of a nationwide hands-on workshop on the diagnostic rates and management of obstetrical anal sphincter Injuries in Israel.

AIM: The aim was to evaluate the influence of a half day, hands-on, workshop on the detection and repair of obstetric anal sphincter injuries (OASIs). METHOD: Starting in February 2011, hands-on workshops for the diagnosis and repair of OASIs were delivered by trained urogynaecologists in departments of tertiary medical centres in Israel. The structure of the hands-on workshop resembles the workshop organized at the International Urogynecological Association annual conferences. Participants included medical staff, midwives and surgical residents from each medical centre. We collected data regarding the rate of OASIs, 1 year before and 1 year following the workshop, in 11 medical centres. The study population was composed of parturients with the following inclusion criteria: singleton pregnancy, vertex presentation and vaginal delivery. Pre-viable preterm gestations (< 24 weeks), birth weight < 500 g, stillborn, and those with major congenital anomalies, multifoetal pregnancies, breech presentations and caesarean deliveries were excluded from the analysis. RESULTS: In the reviewed centres, 70 663 (49.3%) women delivered prior to the workshop (pre-workshop group) and 72 616 (50.7%) women delivered following the workshop (post-workshop group). Third- or fourth-degree perineal tears occurred in 248 women (0.35%) before the workshop, and in 328 (0.45%) following the workshop, a significant increase of 28.7% (P = 0.002). The increase in diagnosis was significant also in women with third-degree tears alone, 226 women (0.32%) before the workshop and 298 (0.41%) following the workshop, an increase of 28.3% (P = 0.005). CONCLUSION: The detection rate of OASIs has significantly increased following the hands-on workshop. The implementation of such programmes is crucial for increasing awareness and detection rates of OASI following vaginal deliveries.

Puerperal ventral epidural hematoma after epidural labor analgesia.

Serious complications in obstetric anesthesia are a rare occurrence. High neuraxial block, respiratory arrest in labor and delivery, and an unrecognized spinal catheter are among the most frequently reported serious complications. A serious complication occurs in approximately 1:3000 obstetric patients. Neuraxial hematoma after obstetric epidural analgesia or anesthesia is extremely rare. We present a case of a puerperal spinal epidural hematoma following epidural labor analgesia. The patient presented with foot drop, which resolved after conservative treatment. We reviewed the epidemiology, clinical manifestations and treatment options for this rare complication.

APOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL.

Oncogenic driver mutations are those that provide a proliferative or survival advantage to neoplastic cells, resulting in clonal selection. Although most cancer-causing mutations have been detected in the protein-coding regions of the cancer genome; driver mutations have recently also been discovered within noncoding genomic sequences. Thus, a current challenge is to gain precise understanding of how these unique genomic elements function in cancer pathogenesis, while clarifying mechanisms of gene regulation and identifying new targets for therapeutic intervention. Here we report a C-to-T single nucleotide transition that occurs as a somatic mutation in noncoding sequences 4 kb upstream of the transcriptional start site of the LMO1 oncogene in primary samples from patients with T-cell acute lymphoblastic leukaemia. This single nucleotide alteration conforms to an APOBEC-like cytidine deaminase mutational signature, and generates a new binding site for the MYB transcription factor, leading to the formation of an aberrant transcriptional enhancer complex that drives high levels of expression of the LMO1 oncogene. Since APOBEC-signature mutations are common in a broad spectrum of human cancers, we suggest that noncoding nucleotide transitions such as the one described here may activate potent oncogenic enhancers not only in T-lymphoid cells but in other cell lineages as well.

Compassion fatigue, burnout and compassion satisfaction in neonatologists in the US.

OBJECTIVE: Compassion fatigue (CF) is distress experienced by caregivers from ongoing contact with patients who are suffering. Burnout (BO) is occupational stress directly related to dissonance between job demands and available resources. Compassion satisfaction (CS) is professional fulfillment experienced through helping others. CF in physicians is not well studied. Neonatologists may be at particular risk for CF by virtue of recurrent exposure to distress in patients and their families. The objectives of this study were to determine the prevalence of CF, BO and CS, and to identify potential predictors for these phenomena in neonatologists. STUDY DESIGN: A modified Compassion Fatigue and Satisfaction Self-Test and a questionnaire of professional details and personal characteristics were distributed electronically to neonatologists nationally. Multivariable logistic and linear regression models for CF, BO and CS as a function of potential predictors were constructed. RESULTS: The survey response rate was 47%. The prevalence of CF, BO and CS was 15.7, 20.8 and 21.9%, respectively. Female gender, emotional depletion, distress from 'a clinical situation', 'co-workers', 'personal health issues' and 'not talking about distressing issues' were each significant determinants of CF. Emotional depletion, distress from the 'physical work environment' and 'co-workers', and 'not talking about distressing issues' were significant determinants of BO. Self-identification as Hispanic; 'not currently feeling distressed'; talking about distressing issues; and utilization of pediatric palliative care services were significant determinants of higher CS. CONCLUSIONS: CF and BO may impact emotional well-being and professional performance of neonatologists. Enhancement of CS is a potential target for intervention.

The role of local estrogen therapy in the management of pelvic floor disorders.

Pelvic floor disorders are common and bothersome problems that include a variety of conditions. These conditions greatly affect the performance of daily activities and social function such as work, traveling, physical exercise, sleep and sexual function. Aging is a well-known factor affecting the pelvic floor and lower urinary tract anatomy and function. It is clear that the pelvic organs and their surrounding muscular and connective tissue support are estrogen-responsive. Treatment of pelvic floor disorders requires significant health-care resources and their impact is likely to increase in the near future. This literature review aims to provide an overview of both research and clinical aspects of the pathophysiology of urogenital estrogen deficiency and the role of local estrogen therapy as part of the management strategy of different pelvic floor disorders. The safety and risk concerns regarding the use of local estrogen therapy are addressed as well.

The spectrum of onset of acute kidney injury in premature infants less than 30 weeks gestation.

OBJECTIVE: To determine risk factors for acute kidney injury (AKI) in preterm infants as a function of time of onset. STUDY DESIGN: In this 5 1/2-year, single-center, retrospective study, incidence and timing of AKI was determined using modified Acute Kidney Injury Network criteria. Characteristics of newborns with and without AKI were compared by chi square and t-tests. Logistic regression was used to examine risk factors for AKI as a function of time of onset and potential confounders. RESULT: AKI occurred in 30.3% of 357 neonates; 72.2% was stage 1. Gestational ages (GA), initial Cr, maternal magnesium and volume resuscitation were associated with early AKI (days 0 to 1). Volume resuscitation, umbilical arterial line and receipt of non-steroidal anti-inflammatory drug (NSAID) for patent ductus arteriosus were associated with intermediate AKI (days 2 to 5). GA, steroids for early hypotension, necrotizing enterocolitis and sepsis were associated with late AKI (⩾day 6). CONCLUSION: Stage 1 AKI is a common morbidity in our population. Risk factors for AKI in our population differed with time of onset.

The origin of endodontic Enterococcus faecalis explored by comparison of virulence factor patterns and antibiotic resistance to that of isolates from stool samples, blood cultures and food.

AIM: To elucidate the origin of Enterococcus faecalis isolated from secondary root canal infections and the possibility for a foodborne transmission by comparing them to strains recovered from food, blood and stool regarding putative virulence factors and antibiotic susceptibility profiles, where strains from common origin were hypothesized to harbour similar characteristics. METHODOLOGY: A total of 108 E. faecalis strains recovered in the county of Stockholm, Sweden, were screened using PCR for putative virulence factors esp, cylA, gelE/gelatinase-negative phenotype (ef1841/fsrC), efaA, ace and asa1. The minimum inhibitory concentration (MIC) for ampicillin, piperacillin-tazobactam, imipenem, gentamicin, vancomycin, ciprofloxacin and linezolid was determined using the agar dilution method. RESULTS: Next to strains from blood, the food isolates presented the highest average number of virulence determinants and were frequently enriched with asa1 coding for aggregation substance. None of the endodontic strains carried cylA, and the gelatinase-negative phenotype caused by a deletion dominated the group. Altogether, the most prevalent genes were gelE, efaA and ace, and a combination of them was equally present in approximately 80% of the strains from food, stool and root canals in comparison with 43.3% of the blood isolates. High-level resistance to ciprofloxacin and gentamicin was observed in 30% of the blood isolates, whereas the isolates from other origins, with single exceptions, were susceptible to all tested antibiotics. CONCLUSIONS: Evidence for a foodborne transmission, explaining the high reported prevalence of E. faecalis in root filled teeth, could not be determined based on the similarities in virulence factor patterns and antibiotic susceptibility. The only linkage between isolates from food and root canals consisted of a shared common combination of the genes gelE, efaA and ace. The high occurrence of putative virulence traits in food isolates questions the safety of E. faecalis in food products.

Long term subjective cure rate, urinary tract symptoms and dyspareunia following mesh augmented anterior vaginal wall prolapse repair.

INTRODUCTION: The aim of this study was to assess patient-centered long term outcomes following anterior vaginal repair with mesh. METHODS: In January 2015, we identified 124 women who underwent anterior pelvic floor repair with mesh between January 2006 and February 2009. Patient records were reviewed and demographic, clinical, intra-operative and post-operative follow-up data retrieved. Telephone interviews were conducted to access information on clinical outcomes. Associations between baseline characteristics and long term symptoms were assessed by multivariable logistic regression models. RESULTS: Seventy-nine women were reached and consented to participate. Patients were interviewed 79-104 months after surgery. Their mean age at the time of surgery was 62.48 ± 9.53 years; all had stage III cystocele with a mean POP Q point Ba of 5.32 ± 1.47. Twenty-four (30%) had a previous hysterectomy and 26 (33%) had a previous pelvic organ prolapse or stress urinary incontinence operation. At telephone interviews, recurrence of prolapse symptoms was reported by 11 (13.9%) patients, mostly in the posterior compartment. Only 6 needed a corrective procedure. One patient had her mesh removed due to dyspareunia. Eleven (13.9%) reported lower urinary tract symptoms other than prolapse, as follows: stress urinary incontinence (1), overactive bladder (8) and dyspareunia (2). CONCLUSION: Long term rates of recurrent prolapse, dyspareunia and lower urinary tract symptoms were low for patients who underwent anterior vaginal wall mesh augmentation surgery for symptomatic cystoceles.

Analysis of effects of MCB3681, the antibacterially active substance of prodrug MCB3837, on human resident microflora as proof of principle.

The water-soluble prodrug MCB3837 is rapidly converted to MCB3681, active against Gram-positive bacterial species, after intravenous infusion. The aim of this study was to prove the principle that MCB3681 is efficacious in vivo by demonstrating its effect on the resident microflora or colonizers of the human skin, nose, oropharynx and intestine. MCB3837 was infused at a daily dose of 6 mg/kg for 5 days. MCB3681 was active against clostridia, bifidobacteria, lactobacilli, enterococci and Staphylococcus aureus, thus proving the principle that MCB3681 is antibacterially efficacious in vivo without affecting the Gram-negative microflora.

Relationship of maternal creatinine to first neonatal creatinine in infants <30 weeks gestation.

OBJECTIVE: To examine the relationship between maternal and neonatal creatinine (Cr) in preterm infants in the context of antenatal and intrapartum maternal and neonatal factors. STUDY DESIGN: In this 5½-year, single-center, retrospective study, paired maternal and neonatal Cr were compared by t-test. Linear regression for correlated outcomes employing generalized estimating equations was used to examine neonatal Cr as a function of antenatal maternal Cr and potential confounders. RESULT: A total of 157 neonates of 124 mothers met study criteria. Neonatal Cr values in the first 24 h of life were significantly higher than antenatal maternal values. Linear regression modeling showed that maternal Cr, neonatal lactate, hypoxic-ischemic villous changes on placental pathology and multiple gestation were each significant determinants of the first neonatal Cr. CONCLUSION: No neonatal Cr was less than its paired maternal value. Maternal Cr, neonatal lactate, hypoxic-ischemic villous changes in the placenta and multiple gestation were each significantly associated with neonatal Cr.

Impact of renal function and protein intake on blood urea nitrogen in preterm infants in the first 3 weeks of life.

OBJECTIVE: To examine the relationship between blood urea nitrogen (BUN) during the first 3 weeks of life and protein intake and creatinine (Cr) and to quantify the effect of protein intake on postnatal growth in preterm infants. STUDY DESIGN: This is a 4-year, single-center, retrospective cohort study. We used multivariable linear regression models to examine the relationships between mean weekly BUN and protein intake adjusted for mean weekly Cr and potential confounders. We used additional regression models to examine the effect of protein intake on growth during this period. RESULT: Overall, 249 infants met study criteria. As protein intake increased over the first 3 weeks of life, both BUN and Cr decreased significantly. Linear regression models showed protein intake and Cr were each significantly associated with mean BUN for each study week. CONCLUSION: Protein intake and Cr were each significantly associated with BUN. Significant amelioration of growth failure was seen with higher protein intake.

Ovarian reserve and PGD treatment outcome in women with myotonic dystrophy.

Myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults. There are conflicting reports about its effect on female fertility. This study investigated ovarian reserve and IVF-preimplantation genetic diagnosis (PGD) outcome in women with DM1. A total of 21 women undergoing PGD for DM1 were compared with 21 age- and body mass index-matched women undergoing PGD for other diseases. Ovarian reserve markers, response to stimulation, embryo quality and clinical pregnancy and live birth rates were compared. Day-3 FSH concentration was higher, while anti-Müllerian hormone concentration and antral follicle count were lower in the DM1 group (median, range: 6.9 (1.8-11.3) versus 5.7 (1.5-10.7)IU/l; 0.9 (0.17-5.96) versus 2.68 (0.5-9.1)ng/ml; and 13 (0-63) versus 23 (8-40) follicles, respectively, all P < 0.05). Total FSH dose was higher (5200 versus 2250 IU, P = 0.004), while the numbers of oocytes retrieved (10 versus 16, P < 0.04) and metaphase-II oocytes (9 versus 12, P < 0.03) were lower in the DM1 group. The number of cycles with top-quality embryos and the clinical pregnancy rate were lower in the DM1 group. In conclusion, there is evidence of diminished ovarian reserve and less favourable IVF-PGD outcome in women with DM1. Myotonic Dystrophy (DM) is the most common form of muscular dystrophy in adults. There is evidence of subfertility in males affected with the disease but conflicting reports about the effect of the disease on female fertility. The aim of our study was to investigate ovarian reserve and IVF-PGD results in women with DM. Twenty-one women undergoing preimplantation genetic diagnosis (PGD) treatment for DM were compared to 21 age- and BMI matched women undergoing PGD treatment for other diseases. The two groups were compared for antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) levels (the best known markers of ovarian reserve and fertility potential), ovarian response, embryo quality and pregnancy and live birth rates. AFC and the AMH levels were statistically significant lower in the DM group. Total medication dose needed for ovarian stimulation was higher, the number of oocytes and mature oocytes retrieved, and the number of cycles with top quality embryos were lower in the DM group compared to the controls. In conclusion, there is evidence of diminished ovarian reserve, and less favorable IVF-PGD outcome in women with DM. Therefore, we recommend advising these women about the possibility of early decreasing ovarian function in order to prevent any delay in reproductive planning.

Is a value of over 200 mg/dL in the oral glucose tolerance test, a marker of severity in patients with gestational diabetes mellitus?

OBJECTIVE: To determine whether blood glucose values of over 200 mg/dL in the oral glucose tolerance test (OGTT) are associated with pregnancy complications and adverse perinatal outcomes in patients with gestational diabetes mellitus (GDM). METHODS: A retrospective cohort study was performed comparing patients with GDM A1 (diet controlled) that had at least one value of 200 mg/dL or higher in the OGTT, to those who did not. Patients were treated at the diabetes day care clinic of a tertiary medical center between the years 1999 and 2010. Data were available from the computerized perinatal databases. RESULTS: During the study period, 778 women with GDM were treated at the diabetes day care clinic. Of these, 162 had at least one test value of 200 mg/dL or greater. No significant differences regarding maternal and perinatal complications, such as polyhydramnios, macrosomia (birth-weight above 4 kg), shoulder dystocia, low Apgar scores at 5 min (<7) and cesarean section were noted between the groups. CONCLUSIONS: A value of 200 mg/dL or more in the OGTT is not an indicator of perinatal complications.

Antibiotic resistance patterns of Escherichia coli isolates from different aquatic environmental sources in León, Nicaragua.

Antibiotic-resistant bacteria have emerged due to the selective pressure of antimicrobial use in humans and animals. Water plays an important role in dissemination of these organisms among humans, animals and the environment. We studied the antibiotic resistance patterns among 493 Escherichia coli isolates from different aquatic environmental sources collected from October 2008 to May 2009 in León, Nicaragua. High levels of antibiotic resistance were found in E. coli isolates in hospital sewage water and in eight of 87 well-water samples. Among the resistant isolates from the hospital sewage, ampicillin, chloramphenicol, ciprofloxacin, nalidixic acid, trimethoprim-sulphamethoxazole was the most common multi-resistance profile. Among the resistant isolates from the wells, 19% were resistant to ampicillin, ceftazidime, ceftriaxone, cefotaxime, chloramphenicol, ciprofloxacin, gentamicin, nalidixic acid and trimethoprim-sulphamethoxazole. E. coli producing ESBL and harbouring bla(CTX-M) genes were detected in one of the hospital sewage samples and in 26% of the resistant isolates from the well-water samples. The bla(CTX-M-9) group was more prevalent in E. coli isolates from the hospital sewage samples and the bla(CTX-M-1) group was more prevalent in the well-water samples.

Antenatal antibiotic exposure in preterm infants with necrotizing enterocolitis.

OBJECTIVE: To determine whether an association exists between antenatal antibiotic exposure and incidence of necrotizing enterocolitis (NEC) in low birth weight infants. STUDY DESIGN: A retrospective case-control study was performed on all infants with a diagnosis of NEC born at our institition between 1988 and 2006. Medical histories of all infants with a diagnosis of NEC ≥Bell's stage IIA and matched controls without NEC were reviewed. Maternal and neonatal characteristics were compared using the Mantel-Haenszel chi-square procedure, and logistic regression models were constructed to account for confounding. RESULT: Clinical data for 97 matched pairs were analyzed. The adjusted odds ratio (OR) for antenatal exposure to ampicillin was significantly greater for infants who developed NEC (OR 2.3, 95% confidence interval 1.1, 4.8, P=0.003) than for control infants. CONCLUSION: Infants who developed NEC were more likely to have a history of in utero exposure to ampicillin in the immediate antepartum period than infants who did not develop NEC.

Comparative effects of the immediate and the extended release formulations of ciprofloxacin on normal human intestinal microflora.

Ciprofloxacin is a well-known fluoroquinolone, active in vitro against most Gram-negative and Gram-positive bacteria. The purpose of the present study was to evaluate the ecological effects of an orally administered extended-release formulation of ciprofloxacin in comparison with an immediate-release formulation of ciprofloxacin on the normal human intestinal microflora. Thirty-six healthy female subjects were included in the study. the extended-release formulation of ciprofloxacin was given as 500 mg once daily and the immediate-release formulation as 250 mg twice daily. The treatment period was 3 days. the microbiological investigation was blinded with respect to treatment. Mean fecal concentration in the volunteers receiving the extended-release formulation ciprofloxacin was 453 mg/kg and in the immediate-release formulation ciprofloxacin volunteers, the mean fecal concentration was 392 mg/kg. The numbers of Escherichia coli were significantly suppressed while the enterococci decreased moderately in both treatment groups. No toxigenic Clostridium difficile strains were found. No major differences were observed between the two studied formulations on the normal human intestinal microflora.

Antibiotic resistance patterns in gram-negative and gram-positive bacteria causing septicemia in newborns in León, Nicaragua: correlation with environmental samples.

The aim of this study was to identify the bacteria causing neonatal septicemia in a neonatal intensive care unit (NICU) in León, Nicaragua and its relation with bacteria isolated from the environment at the NICU. Our data showed that 74% (34/46) of the bacteria related to newborns with septicemia were Gram-negative and highly resistant to beta-lactams (>85%) and aminoglycosides (80%), leading to treatment failure in 10 neonates with fatal outcome. Although, the prevalence of Gram-positive bacteria (26%) was lower than Gram-negative bacteria, Staphylococcus epidermidis was related to the death of three newborns. No clonal similarity was found among Enterobacter cloacae , Escherichia coli and Serratia liquefaciens isolated from the neonates with septicemia and the NICU environment. However, in order to improve the outcome for neonates with septicemia, infection control practices and appropriate empirical therapy should be considered to reduce the high prevalence of extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria isolated from neonates with septicemia (80%) and from the NICU environment (34%).

Prostanoid DP receptor (PTGDR) variants in mothers with post-coital associated preterm births: preliminary observations.

OBJECTIVE: To describe prostanoid DP receptor (PTGDR) variants in women with preterm births who admitted to coital activity (CA) within 24 h of labor. STUDY DESIGN: To achieve >80% statistical power, a pilot case-control study compared 24 premature births from mothers with CA (Group 1), 30 mothers of premature infants who did not have CA (Group 2 non-coital activity) and 95 non-coital activity mothers with term births (Group 3 controls). Four functional PTDGR single nucleotide polymorphisms (SNPs) were evaluated: T-549C, C-441/T, T-197C and G+1044A. PHASE 2.0.2 and SAS 9.2 were used for analysis. RESULT: All SNPs were in Hardy-Weinberg equilibrium in controls. The C-441/T genotype frequency was significantly increased among Group 1 women relative to Group 2 and 3 women (odds ratio (OR): 30.1, 95% confidence interval (CI) 6.9-191 and 25.7 95%CI 25.7-not computible, respectively). Of the possible haplotypes among the groups, the TCTG haplotype (T-549C, C-441/T, T-197C and G+1044A) was significantly more frequent in Group 1 women compared with the control groups (OR 53.4, 95%CI 10.3-554.8). CONCLUSIONS: A differential genomic pattern of PTGDR polymorphisms was identified in a sub-set of mothers which was associated with an increased risk of post-coital preterm birth.

Distinct ribotypes and rates of antimicrobial drug resistance in Clostridium difficile from Shanghai and Stockholm.

Seventy-five clinical isolates of Clostridium difficile from Shanghai and 80 from Stockholm were investigated. The prevalence of toxin A-negative, toxin B-positive isolates of C. difficile among isolates from Shanghai (33.3%) was significantly higher than among isolates from Stockholm (0%). Both sets of isolates were fully susceptible to metronidazole and vancomycin. However, the MICs of fluoroquinolones, erythromycin-clindamycin, tetracycline, rifampin and fusidic acid were significantly higher for the Shanghai isolates than for the Stockholm isolates. Thirty-three PCR ribotypes were identified; a dominant clone, 017, accounted for 18.7% of Shanghai isolates, whereas clone 005 dominated among Stockholm isolates, accounting for 11.3%. Strains 027 and 078 were not detected. No outbreak occurred during the study period.