A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer.

Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9-10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.

Adnexal torsion recurrence-is the adnexal twist degree a risk factor? A retrospective cohort study.

OBJECTIVE: To evaluate whether the adnexal twist degree is related to torsion recurrence and whether there is a dose-dependent correlation. DESIGN: A retrospective cohort study. SETTING: Single tertiary medical centre. POPULATION: The study includes non-pregnant patients operated, for the first time, for adnexal torsion, between 2011 and 2018. METHODS: Information regarding the degree of adnexal twist was collected from surgical reports. Recurrence was identified using a computerised database and ascertained via telephone with a response rate of 87.2% (253/290). MAIN OUTCOME MEASURES: Adnexal torsion recurrence rate. RESULTS: A total of 182 women who had undergone laparoscopic detorsion met the inclusion criteria. Twenty-two had torsion recurrence (12.1%). Adnexal twist degree in the primary event was associated with a higher recurrence risk: 4.3% of women with twist degree ≤360 (n = 3/70), 14.5% of women with twist degree of 361-720 (n = 9/62) and 20% of women with twist degree >720 (n = 10/50) (P = 0.03). The median twist degree was 540 (interquartile range [IQR] 360-855) and 720 (IQR 675-1080) degrees in the control and study groups, respectively (P = 0.005). Additional possibly associated factors for recurrence were evaluated. Age emerged as a possible risk factor, with a median age of 19 years in the recurrence group (IQR 14-27 years) versus 28.5 (IQR 19-36 years) in the non-recurrence group (P < 0.01). Logistic regression analysis revealed that together with age, adnexal twist degree remained significantly associated with torsion recurrence (odds ratio [OR] 1.98, 95% CI 1.09-3.61; P = 0.02). CONCLUSION: Adnexal twist degree was found to be positively associated with the risk of torsion recurrence. TWEETABLE ABSTRACT: Adnexal twist degree was found to be positively associated with the risk of torsion recurrence.

A thematic literature review of innovative strategies to prepare nursing students for aged-care.

BACKGROUND: The exponential rise in people living longer but requiring residential care is adding pressure to already overstretched aged care nurses. Consequently, a person-centred care culture in residential care remains aspirational, rather than a reality. For nursing students in Australia and elsewhere, clinical placements in aged care facilities are under-utilised due to negative perceptions about the likelihood for learning. Creative strategies to engage students to safely challenge ageist thinking and to inspire enthusiasm for learning in this context are needed. OBJECTIVES: The purpose of this thematic review of the literature is to better understand challenges related to learning in aged care settings and identify innovative strategies to enhance nursing student learning experiences in residential aged care placements. REVIEW METHODS: A literature review was undertaken in 2019 using CINAHL, PUBMED, Elsevier, Medline, ProQuest and Google Scholar. The search was limited to papers that were peer reviewed, in English, and published between 2001 and the date of review (mid-2019) in order to situate the review in the new millennium. RESULTS: 47 articles and books were included in the review that introduce solutions and innovative strategies that could be used to improve students' attitudes to learning in aged care and from older people. The literature review was categorized into three main themes, including: barriers to working with older people; the need for pedagogical change to foster empathy; and innovative strategies to address barriers. CONCLUSION: These themes are useful to consider in designing engaging learning and teaching for nursing students to be effective in working in aged care.

The cost of intraoperative adverse events in abdominal and pelvic surgery: A systematic review.

BACKGROUND: The assessment of intra-operative adverse events (iAEs) is a vastly under researched area with the potential to provide new methods on how to improve patient outcomes and hospital costs. Our objective was to determine the relationship between iAEs and total hospital costs in abdominal and pelvic surgery. DATA SOURCES: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Embase, MEDLINE and EBM Reviews online databases were searched to identify all studies that reported iAE rates and total hospital costs. We then analyzed the costing approach used in each article using the Drummond tool and evaluated articles quality using the GRADE method. CONCLUSIONS: In total, 1709 unique references were identified through our literature search. After review, 23 were included. All studies that reported iAE rates and cost as the primary outcome found that iAEs significantly increased total hospital costs. We identified a relationship between iAEs and increased hospital costs. Future studies need to be performed to further evaluate the relationship between iAEs and cost as current studies are of low quality.

Systematic review to establish absolute standards for technical performance in surgery.

BACKGROUND: Standard setting allows educators to create benchmarks that distinguish between those who pass and those who fail an assessment. It can also be used to create standards in clinical and simulated procedural skill. The objective of this review was to perform a systematic review of the literature using absolute standard-setting methodology to create benchmarks in technical performance. METHODS: A systematic review was conducted by searching MEDLINE, Embase, PsycINFO and the Cochrane Database of Systematic Reviews. Abstracts of retrieved studies were reviewed and those meeting the inclusion criteria were selected for full-text review. The quality of evidence presented in the included studies was assessed using the Medical Education Research Study Quality Instrument (MERSQI), where a score of 14 or more of 18 indicates high-quality evidence. RESULTS: Of 1809 studies identified, 37 used standard-setting methodology for assessment of procedural skill. Of these, 24 used participant-centred and 13 employed item-centred methods. Thirty studies took place in a simulated environment, and seven in a clinical setting. The included studies assessed residents (26 of 37), fellows (6 of 37) and staff physicians (17 of 37). Seventeen articles achieved a MERSQI score of 14 or more of 18, whereas 20 did not meet this mark. CONCLUSION: Absolute standard-setting methodologies can be used to establish cut-offs for procedural skill assessments.

Severe intraabdominal bleeding caused by endometriotic lesions during the third trimester of pregnancy.

OBJECTIVE: Endometriosis is known to be associated with an increased risk for early pregnancy complications, including ectopic pregnancy and miscarriage. However, little has so far been reported on complications linked to severe endometriosis occurring during the third trimester of pregnancy. STUDY DESIGN: A retrospective review of 800 women attending the endometriosis clinic of the Sheba Medical Center during the years 2002-2006 was performed. Cases with severe endometriosis and associated complications during late pregnancy were identified. RESULTS: Three women were found who experienced significant intraabdominal bleeding in the third trimester of pregnancy attributed to a lesion resulting from severe endometriosis. The intraabdominal bleeding occurred between 26-29 weeks of gestation. In all cases the major presenting prenatal symptom was severe lower abdominal pain. The pain was not relieved by the administration of tocolytics or mild analgesics. Explorative laparotomy, performed in all 3 cases, revealed the presence of significant intraabdominal bleeding requiring immediate transfusion of blood products stemming from endometriotic lesions. Fetal complications occurred in all 3 cases. CONCLUSION: The symptoms of endometriosis are often relieved during pregnancy. Yet lesions caused by severe endometriosis can lead to significant intraabdominal bleeding during the third trimester of the pregnancy. Physicians must be aware that close antenatal follow-up and prompt intervention may be required in such cases.

Long-term intermittent compression increases arteriographic collaterals in a rabbit model of femoral artery occlusion.

OBJECTIVES: To assess the effects of intermittent limb compression on arterial collateral formation in a rabbit-model. DESIGN: Animal study. MATERIAL AND METHODS: New Zealand rabbits (n=11), aged 2-years, weight of at least 4.0 kg, underwent bilateral superficial femoral artery ligation. In ten of these, the experimental leg underwent 60 minutes of daily intermittent compression for a ten week period with 3 sec/90 mmHg pressure inflation and a cycle of 3 times per minute. The contra-lateral limbs were not treated. At the end of the ten-week period, high-resolution angiograms were obtained by barium infusion into the aorta. The angiograms were analyzed in a blinded manner and the number of collateral arteries larger than 100 microns, was counted. Following perfusion-fixation, histological specimens of transverse sections of the compressed semi-membranous muscle were examined. RESULTS: The compressed limbs demonstrated a significantly (8.1+/-.87 vs 6.0+/-.97; p<0.005) greater number of collateral vessels, ranging in size from 100-700 microns, as compared to the control sides. The mean size of collaterals in the compressed limbs was not significantly different (0.33+/-0.17 vs 0.31+/-0.16). Microscopic examination of the collaterals confirmed remodeling by a typical neo-intima consisting of 6-7 cell-layers. CONCLUSIONS: Intermittent limb compression increases the number of angiographical collateral arteries.

Quantitative analysis of organ tissue damage after septic shock.

The objective of this study was to quantify end-organ damage caused by bacteremic sepsis. Twelve adult swine were divided into two groups. The anesthesia control group (n = 6) received general anesthesia for 4 hours. The septic shock group (n = 6) received an infusion of Aeromonas hydrophila under general anesthesia for 4 hours. Swine were sacrificed at the end of the 4-hour procedure. Tissues from lungs, kidneys, livers, and hearts were stained with hematoxylin and eosin. Images of tissues were studied with digital image analysis. In lungs, cytoplasmic area (CA), nuclear area (NA), intra-alveolar hemorrhage (IAH), total airspace (TAS), and alveolar septum thickness (ST) were measured. Nuclear and cytoplasmic intensities (NI and CI) were measured in integrated optical density units (IOD). In kidneys, livers, and hearts, CA, CI, NA, and NI were measured similarly. Sinusoidal blood in the liver and vacuolization (VAC) in the kidney were also measured. In septic lungs, CI, NA, NI, ST, IAH, TAS, and ratios of NA/CA, NI/CI, and IAH/TAS were significantly increased compared with the control (P < 0.02). In septic kidneys, CI, NA, VAC, NA/CA, and NI/CI were significantly increased (P < 0.0005). In livers, CA, CI, and NI/CI were significantly increased (P < 0.005). In hearts, the ratios of NA/CA and NI/CI were statistically significant. End organs from septic swine, with exception of the heart, showed significantly higher levels of cellular damage. Digital image analysis provides an objective, precise, and accurate method of quantifying image characteristics. Automating these tasks is a high priority in the research and clinical community in providing a reproducible method for longitudinal analysis of various biological studies.

Transvaginal ultrasound and diagnostic hysteroscopy as a predictor of endometrial polyps: risk factors for premalignancy and malignancy.

The aim of this study is to assess accuracy of transvaginal ultrasound (TVUS) and diagnostic hysteroscopy in diagnosing endometrial polyps and to determine premalignancy and malignancy rates in asymptomatic women. The study was designed to retrospectively analyze 438 women who underwent operative hysteroscopy in a day-care unit when endometrial polyp was suspected after TVUS and diagnostic hysteroscopy. Multivariate logistic regression modeling showed effects of age, previous breast cancer with tamoxifen treatment, and menopause with or without bleeding on pathologic results. The results indicate that positive predictive value of TVUS with diagnostic hysteroscopy was 79.9%. Premalignancy or malignancy occurred in 3.2% and was significantly related to menopause with abnormal bleeding (P < 0.001), which carried a 20-fold higher risk of pathology than any other group. Age was also a risk factor. It was concluded that TVUS with diagnostic hysteroscopy reliably evaluates endometrial polyps. The low incidence of endometrial tumors in asymptomatic (especially premenopausal) women suggests that their operative evaluation may not be cost effective. Larger studies are needed to support this tentative conclusion.

[Medical termination of pregnancy with mifepristone--initial experience at the Sheba Medical Center].

OBJECTIVE: To assess the early implementation of medical termination of pregnancy as an alternative treatment option for women in early pregnancy who wish to avoid a surgical procedure. METHODS: The use of mifepristone (RU-486) for medical termination was recently approved in Israel. We performed a prospective follow-up study of the 189 women who underwent medical termination of pregnancy with mifepristone and misoprostol in our center between January 2000 and April 2001. RESULTS: Complete outcome data was obtained for 176 women. Within this group 152 women (86.4%) did not need any surgical procedure to complete the abortion. Uterine curettage was performed in 17 (9.6%) and operative hysteroscopy in 7 (4.0%) of the women because of incomplete abortion or suspected residua of pregnancy. CONCLUSION: Medical abortion offers an efficient and safe treatment option to women who wish to avoid surgical evacuation.

Outcome of twin pregnancies with extreme weight discordancy.

The objective of this paper is to examine the outcome of pregnancies with extreme weight-discordant twins. Percentage of birth weight discordancy was defined as the birth weight difference between the twins divided by the larger twin's weight and multiplied by 100. Discordancy was calculated for all twin births in which both fetuses were live born. In 33 pairs, the discordancy was defined as extreme (>35%) and they constituted the study group. Thirty-three pairs of twin defined with mild weight discordancy (15-25%), and 33 pairs defined as concordant to birth weight (<15% difference) were matched to the study group patients based on gestational age at delivery (+/- 7 days) and on the mode of delivery, and constituted the control groups. The records of all the patients were reviewed for pregnancy complications and for major and minor neonatal outcome variables. Significantly more parturients in the study groups were primiparous undergoing in vitro fertilization treatments to conceive. Significantly more women in the study group had severe preeclampsia compared with women with mild discordancy or concordant twins (12.1 vs. 3.0% and 0%, respectively, p <0.025). No significant differences were encountered between the groups in neonatal mortality or morbidity factors except an increased rate of hyperbilirubinemia in the study group, p = 0.006. Using logistic regression analysis, discordancy was not defined as an efficient predictor for adverse neonatal outcome. Twin pregnancies with extreme discordancy have a favorable neonatal outcome in correlation with gestational age and not with the percentage of discordancy.

Comparison of cervical vacuum cup cannula with metal cannula for hysterosalpingography.

OBJECTIVE: The aim of this study was to compare the use of a cervical vacuum cap cannula with the traditional metal cannula. DESIGN: A prospective, randomised, single-blinded comparative study. SAMPLE: Fifty consecutive infertile women undergoing hysterosalpingography for evaluation of infertility METHODS: Hysterosalpingography was performed either with the traditional metal cannula (n = 25) or a cervical vacuum cap cannula (n = 25). MAIN OUTCOME MEASURES: Length of procedure, fluoroscopic time, amount of contrast medium, pain to the patient while applying the cannula and injecting the contrast medium, level of difficulty to the performer, the need to reapply the cannula, complications, and results of the hysterosalpingography. RESULTS: Using the cervical vacuum cap cannula, compared with the metal cannula, the duration of the procedure was significantly shorter (5.3 vs 9.3 minutes; P < 0.001), less fluoroscopic time was needed (0.9 vs 1.8 minutes; P < 0.001), a smaller amount of contrast medium was used (4.6 vs 15.7 mL; P < 0.001), the procedure caused less pain to the patient (3.2 vs 6.8, respectively; on a scale of 1-10; P < 0.001), and was easier for the physician to perform (1.4 vs 3.4; on a scale of 1-10; P < 0.001). No significant differences were encountered between the two groups in the need to reapply the cannula, in the rate of complications or in the results of the hysterosalpingography. CONCLUSIONS: The cervical cap cannula appears to be superior to the traditional metal cannula for performing hysterosalpingography.

The accuracy of serum interleukin-6 and tumour necrosis factor as markers for ovarian torsion.

BACKGROUND: The aim of this study was to investigate a possible role for interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) as pre-operative markers for the diagnosis of ovarian torsion. METHODS: Twenty consecutive patients admitted to the gynaecological emergency room with suspected clinical diagnosis of ovarian torsion were prospectively assigned to the study. Blood samples were drawn pre-operatively and examined for serum concentrations of IL-6 and TNF-alpha. Surgeons were blinded to laboratory results prior to laparoscopy. RESULTS: The pre-operative diagnosis of ovarian torsion was confirmed during an urgent diagnostic laparoscopy in 8 (40%) patients. The surgical diagnosis among the remaining 12 patients was a large ovarian cyst not in torsion. In six out of eight (75.0%) patients with ovarian torsion serum IL-6 concentrations were elevated. None of the 12 patients without torsion had elevated serum IL-6 concentrations. This difference was statistically significant (P < 0.001). There was no significant difference in the proportion of women with elevated serum TNF-alpha concentrations, two of eight (25.0%) patients with torsion and four of 12 (33.3%) control cases. CONCLUSIONS: Elevated serum IL-6 concentrations, but not serum TNF-alpha concentrations, were significantly associated with the occurrence of ovarian torsion. In patients with vague clinical signs of ovarian torsion, serum IL-6 might help to distinguish which patients should undergo diagnostic laparoscopy.

Sonohysterography for the diagnosis of residual trophoblastic tissue.

OBJECTIVE: To assess the efficacy, safety, and associated complications of sonohysterography for the diagnosis of residual trophoblastic tissue. METHODS: We conducted a prospective study of 23 consecutive patients admitted to our ultrasonography unit with clinical and ultrasonographic signs of retained intrauterine tissue. RESULTS: Twelve patients had hydrosonographic features suggestive of residual trophoblastic tissue (i.e., an intrauterine lesion not detachable from the uterine wall after instillation of saline), whereas in 11 cases the hydrosonographic findings were negative for retained tissue. Blood flow was detected within abnormal intrauterine masses in 4 of 12 patients with trophoblastic tissue, whereas it was not detected in any patient without retained tissue (P = .093). No complications were encountered during the procedure or the postprocedure period. None of the patients had anesthetic complications, perforation of the uterus, fluid overload, or any other surgical complication. All 12 patients underwent hysteroscopic removal of the suspected residual trophoblastic tissue, and histologic confirmation of residual trophoblastic tissue was obtained in all cases. CONCLUSIONS: Sonohysterography for detection and diagnosis of residual trophoblastic tissue is an accurate and safe procedure. Further studies comparing the efficacy of sonohysterography with that of diagnostic hysteroscopy are warranted.

Double-blind, placebo-controlled trial of famotidine in children with abdominal pain and dyspepsia: global and quantitative assessment.

To determine the benefit of using an H2-receptor antagonist in children with abdominal pain and dyspepsia, 25 such children were enrolled in a double-blind, placebo-controlled trial of famotidine. Global and quantitative pain assessments were done before and after each treatment period. The quantitative assessment was calculated based on the abdominal pain score that was the sum of three components. Based on the global evaluation, there was a clear benefit of famotidine over placebo (68% vs 12%). Using the quantitative assessment, however, the mean improvement of the score using famotidine versus placebo was not statistically significant (3.37+/-3.53 vs 1.66+/-2.7). There was a significant improvement in this score during the first treatment period regardless of medication used (period effect: P = 0.05). A subset of patients with peptic symptoms demonstrated a significant drug effect that outweighed the period effect (drug effect: P = 0.01; period effect: P = 0.02). We conclude that famotidine subjectively improves the symptoms of children with recurrent abdominal pain but not objectively using the derived score. However, famotidine is significantly more effective than placebo among children with peptic symptoms. The use of this simple scoring scale may facilitate selecting those children who will benefit from H2-receptor antagonist therapy.

Hysteroscopy may be the method of choice for management of residual trophoblastic tissue.

STUDY OBJECTIVE: To assess the efficacy of and reproductive outcome after selective curettage of residual trophoblastic tissue directed by hysteroscopy compared with conventional, nonselective, blind curettage. DESIGN: Retrospective analysis (Canadian Task Force classification II-1). SETTING: Tertiary care medical center. PATIENTS: Seventy patients after curettage or delivery, with clinical and ultrasonographic signs of suspected residual trophoblastic tissue. MEASUREMENTS AND MAIN RESULTS: Twenty-four women underwent traditional curettage and 46 underwent hysteroscopic selective curettage. Five (20.8%) patients who underwent traditional curettage later required operative hysteroscopy due to persistent residual tissue. None of those who underwent hysteroscopic selective curettage needed a second operation. No patient in either group experienced anesthetic complications, perforation of the uterus, fluid overload, or other surgical complication. Reproductive outcome was similar in both groups, with tendency to conceive earlier in the hysteroscopy group, but no difference in overall pregnancy rates. CONCLUSION: Operative hysteroscopy for selective curettage of residual trophoblastic tissue should be considered an alternative to nonselective, blind curettage.

A randomized prospective comparative study of general versus epidural anesthesia for transcervical hysteroscopic endometrial resection.

OBJECTIVE: This study was undertaken to compare general versus epidural anesthesia during hysteroscopic endometrial resection for dysfunctional uterine bleeding. STUDY DESIGN: In a prospective comparative study, 24 women with abnormal uterine bleeding that was unresponsive to conservative medical management were randomly assigned to undergo hysteroscopic endometrial resection with either general or epidural anesthesia. RESULTS: The durations of the endometrial resection procedure were similar for women who had general and epidural anesthesia (28.3 +/- 4.2 minutes vs 27.5 +/- 5.4 minutes, respectively). However, there was a statistically significantly lower absorption of distention fluid in women who underwent the procedure with general rather than epidural anesthesia (380.8 +/- 158.2 mL vs 648.3 +/- 157.1 mL, respectively; P < .0005). CONCLUSION: A significantly lower amount of glycine distention fluid was absorbed during endometrial resection in women who underwent the procedure with general rather than epidural anesthesia.