Publications by authors named "Christoph Wohlmuth"

22 Publications

  • Page 1 of 1

Oncologic outcomes of endometrial cancer in patients with low-volume metastasis in the sentinel lymph nodes: An international multi-institutional study.

Gynecol Oncol 2021 Jul 14. Epub 2021 Jul 14.

Turkish Society of Gynecologic Oncology, Istanbul, Turkey; Department of Gynecologic Oncology, Koc University School of Medicine, Istanbul, Turkey.

Objective: To assess oncologic outcomes in endometrial cancer patients with low-volume metastasis (LVM) in the sentinel lymph nodes (SLNs).

Methods: Patients with endometrial cancer and SLN-LVM (≤2 mm) from December 3, 2009, to December 31, 2018, were retrospectively identified from 22 centers worldwide. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV, adnexal involvement, or unknown adjuvant therapy (ATx) were excluded.

Results: Of 247 patients included, 132 had isolated tumor cell (ITC) and 115 had micrometastasis (MM). Overall 4-year recurrence-free survival (RFS) was 77.6% (95% CI, 70.2%-85.9%); median follow-up for patients without recurrence was 29.6 (interquartile range, 19.2-41.5) months. At multivariate analysis, Non-endometrioid (NE) (HR, 5.00; 95% CI, 2.50-9.99; P < .001), lymphovascular space invasion (LVSI) (HR, 3.26; 95% CI, 1.45-7.31; P = .004), and uterine serosal invasion (USI) (HR, 3.70; 95% CI, 1.44-9.54; P = .007) were independent predictors of recurrence. Among 47 endometrioid ITC patients without ATx, 4-year RFS was 82.6% (95% CI, 70.1%-97.2). Considering 18 ITC patients with endometrioid grade 1 disease, without LVSI, USI, or ATx, only 1 had recurrence (median follow-up, 24.8 months).

Conclusions: In patients with SLN-LVM, NE, LVSI, and USI were independent risk factors for recurrence. Patients with any risk factor had poor prognosis, even when receiving ATx. Patients with ITC and grade 1 endometrioid disease (no LVSI/USI) had favorable prognosis, even without ATx. Further analysis (with more patients and longer follow-up) is needed to assess whether ATx can be withheld in this low-risk subgroup.
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http://dx.doi.org/10.1016/j.ygyno.2021.06.031DOI Listing
July 2021

Vulvar Melanoma: Molecular Characteristics, Diagnosis, Surgical Management, and Medical Treatment.

Am J Clin Dermatol 2021 Jun 14. Epub 2021 Jun 14.

Department of Dermatology and Allergology, Paracelsus Medical University, Salzburg, Austria.

Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate of cutaneous melanoma has dropped by 7% annually during the last 5 years, the prognosis of vulvar melanoma remains dismal: the 5-year overall survival rate is 47% compared with 92% for cutaneous melanoma. The current evidence suggests that this likely results from a combination of delayed diagnosis and different tumor biology, treatment strategies, and treatment response. Although many landmark trials on checkpoint inhibitors included mucosal and vulvar melanomas, the results were often not reported separately. Post-hoc analyses indicate overall response rates between 19 and 37% for checkpoint inhibitors. A recently published retrospective study on vulvar melanomas suggests an objective response in 33.3% with a similar safety profile to cutaneous melanoma. Tyrosine kinase inhibitors may be considered in recurrent disease if a c-KIT mutation is present.
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http://dx.doi.org/10.1007/s40257-021-00614-7DOI Listing
June 2021

Gynecologic Malignancies in Children and Adolescents: How Common is the Uncommon?

J Clin Med 2021 Feb 12;10(4). Epub 2021 Feb 12.

Department of Dermatology, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria.

The aim of this study is to assess the projected incidence and prognostic indicators of gynecologic malignancies in the pediatric population. In this population-based retrospective cohort study, girls ≤18 years with ovarian, uterine, cervical, vaginal and vulvar malignancies diagnosed between 2000 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER)-18 registry. The Kaplan-Meier method was used to analyze overall survival (OS). The age-adjusted annual incidence of gynecologic malignancies was 6.7 per 1,000,000 females, with neoplasms of the ovary accounting for 87.5%, vagina 4.5%, cervix 3.9%, uterus 2.5% and vulva 1.6% of all gynecologic malignancies. Malignant germ-cell tumors represented the most common ovarian neoplasm, with an increased incidence in children from 5-18 years. Although certain subtypes were associated with advanced disease stages, the 10-year OS rate was 96.0%. Sarcomas accounted for the majority of vaginal, cervical, uterine and vulvar malignancies. The majority of vaginal neoplasms were observed in girls between 0-4 years, and the 10-year OS rate was 86.1%. Overall, gynecologic malignancies accounted for 4.2% of all malignancies in girls aged 0-18 years and the histologic subtypes and prognosis differed significantly from patients in older age groups.
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http://dx.doi.org/10.3390/jcm10040722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918615PMC
February 2021

Clinical Characteristics and Treatment Response With Checkpoint Inhibitors in Malignant Melanoma of the Vulva and Vagina.

J Low Genit Tract Dis 2021 Apr;25(2):146-151

Objectives: The aims of the study were to assess the clinical and histopathological characteristics of a comprehensive cohort of women with vulvovaginal melanoma (VVM) treated at our institution and to study the treatment response of checkpoint inhibitors in this patient cohort.

Materials And Methods: This is a retrospective study of women with invasive VVM treated at the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, over a period of 15 years. Clinical and histopathological characteristics, treatment, as well as treatment-related outcome were analyzed in 32 women. Treatment response was evaluated retrospectively using the "response criteria for use in trials testing immunotherapeutics" (iRECIST). The objective response rate was defined as the proportion of patients with complete or partial response based on the best overall response.

Results: At a median follow-up of 37.8 months (5.8-110.4), 26 women (81.3%) had disease progression and 16 (50%) died. Thirteen patients with locally unresectable or metastatic melanoma were treated with immune checkpoint inhibitors. Ten additional cases were identified from previously published reports. The best objective response rate for immune checkpoint inhibitors was 30.4% (95% CI = 11.6%-49.2%) and the clinical benefit rate was 52.2% (95% CI = 31.8%-72.6%). The clinical benefit rate was significantly better for programmed cell death protein 1 inhibitors (or a combination) compared with ipilimumab alone (Fisher exact, p = .023). Grade 3/4 adverse events were observed in 3 (13.0%) of the 23 patients.

Conclusions: Women with VVM constitute a high-risk group with poor overall prognosis. Immune checkpoint inhibitors are effective in the treatment of metastatic melanoma in this patient cohort.
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http://dx.doi.org/10.1097/LGT.0000000000000583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984764PMC
April 2021

High-throughput approaches for precision medicine in high-grade serous ovarian cancer.

J Hematol Oncol 2020 10 9;13(1):134. Epub 2020 Oct 9.

Department of Medical Biophysics, University of Toronto, Toronto, Canada.

High-grade serous carcinoma (HGSC) is the most prevalent and aggressive subtype of ovarian cancer. The large degree of clinical heterogeneity within HGSC has justified deviations from the traditional one-size-fits-all clinical management approach. However, the majority of HGSC patients still relapse with chemo-resistant cancer and eventually succumb to their disease, evidence that further work is needed to improve patient outcomes. Advancements in high-throughput technologies have enabled novel insights into biological complexity, offering a large potential for informing precision medicine efforts. Here, we review the current landscape of clinical management for HGSC and highlight applications of high-throughput biological approaches for molecular subtyping and the discovery of putative blood-based biomarkers and novel therapeutic targets. Additionally, we present recent improvements in model systems and discuss how their intersection with high-throughput platforms and technological advancements is positioned to accelerate the realization of precision medicine in HGSC.
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http://dx.doi.org/10.1186/s13045-020-00971-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547483PMC
October 2020

Cytology-based screening for anal intraepithelial neoplasia in women with a history of cervical intraepithelial neoplasia or cancer.

Cancer Cytopathol 2021 02 1;129(2):140-147. Epub 2020 Oct 1.

Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: High-risk human papillomavirus (HPV) has been identified in the pathogenesis of anal cancer. The purpose of this study was to assess the prevalence of abnormal anal cytology and HPV in women aged ≥40 years who have a history of high-grade cervical squamous intraepithelial lesion (SIL) or cancer and to estimate the prevalence of anal intraepithelial neoplasia (AIN) using cytology as the primary screening modality.

Methods: Women who had a history of high-grade cervical SIL or cancer and were ≥40 years of age were included in this prospective study. Anal cytology with HPV-DNA testing was performed. All patients with abnormal anal cytology were referred for high-resolution anoscopy (HRA), and abnormal lesions were biopsied and treated if pathologically confirmed. Abnormal anal cytology correlated with HPV status, HRA findings, and clinical and demographic characteristics.

Results: A total of 317 women completed the study. Of these, 96 (30.3%) had abnormal anal cytology (high-grade SIL, 12.5%; low-grade SIL, 19.8%; atypical squamous cells, cannot exclude high-grade SIL, 6.3%; atypical squamous cells of undetermined significance, 61.5%) and 101 (31.9%) were HPV-DNA-positive. There was a significant association between abnormal cytology results and the presence of high-risk HPV. Of the 96 patients with abnormal cytology, 30 (31.3%) had biopsy-proven AIN on HRA, representing 9.5% of the total patient cohort; of these, 10 (33.3%) had low-grade AIN and 20 (66.7%) had high-grade AIN. Older age and smoking were significant risk factors for abnormal anal cytology.

Conclusion: Women aged ≥40 years with a history of high-grade cervical SIL or cancer have a high rate of AIN. Screening for anal cancer may therefore be considered in this patient population. The optimal screening approach should be addressed in future studies.
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http://dx.doi.org/10.1002/cncy.22360DOI Listing
February 2021

Vulvamalignome: eine interdisziplinäre Betrachtung.

J Dtsch Dermatol Ges 2019 Dec;17(12):1257-1276

Universitätsklinik für Dermatologie und Allergologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich.

Vulvamalignome stellen die vierthäufigste Gruppe von gynäkologischen Krebserkrankungen dar. Erste Ansprechpartner sind typischerweise niedergelassene Dermatologen und Gynäkologen. Mit der jeweiligen Fachexpertise findet die Diagnose und Therapie idealerweise interdisziplinär zwischen spezialisierten Dermatoonkologen und gynäkologischen Onkologen statt. Vulvamalignome sind überwiegend Erkrankungen des höheren Lebensalters, obwohl alle histologischen Subtypen auch bei Frauen unter 30 Jahren vorkommen. Die Diagnose erfolgt oft verzögert. Eine genaue Kartierung von Biopsien (Mapping) ist von großer Bedeutung, da Lokalisation und Entfernung von der Mittellinie in Abhängigkeit von der zugrunde liegenden Histologie das operative Vorgehen bestimmen. Plattenepithelkarzinome machen mehr als 76 % der Vulvamalignome aus und vulväre intraepitheliale Neoplasien (VIN) sind dabei wichtige Vorstufen. Der zweithäufigste Typ der Vulvakarzinome ist das Basalzellkarzinom. Melanome machen 5,7 % der vulvären Malignome aus und ihre Prognose ist schlechter als die der kutanen Melanome. Die meisten Studien zu Checkpoint-Inhibitoren und zielgerichteten Therapien haben Patientinnen mit vulvären Melanomen nicht ausgeschlossen. Die vorliegende Evidenz wird im folgenden diskutiert. Die Methode der Wahl bei lokal resezierbaren Vulvamalignomen ist die Exzision. Angesichts ihrer Seltenheit sollte die Behandlung in spezialisierten Zentren erfolgen, um eine optimale Krankheitskontrolle zu erreichen und Kontinenz und sexuelle Funktion bestmöglich zu erhalten.
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http://dx.doi.org/10.1111/ddg.13995_gDOI Listing
December 2019

Vulvar malignancies: an interdisciplinary perspective.

J Dtsch Dermatol Ges 2019 12 12;17(12):1257-1276. Epub 2019 Dec 12.

Department of Dermatology, Paracelsus Medical University Salzburg, Austria.

Vulvar cancer represents the fourth most common gynecologic malignancy and is often encountered by the general Dermatologist or Gynecologist. Dermatooncologists and Gynecologic Oncologists share expertise in this field and the diagnosis and treatment should ideally be interdisciplinary. All subtypes are typically seen in the later decades of life, although all histologic subtypes have been described in women younger than 30 years. The diagnosis is often delayed. Exact mapping of biopsies is of high importance, as the location and distance from the midline guides the surgical approach depending on the underlying histology. Squamous cell carcinoma accounts for more than 76 % of vulvar cancer with vulvar intraepithelial neoplasia being an important precursor. Basal cell carcinoma is the second most common vulvar malignancy. Melanoma accounts for 5.7 % of vulvar cancer and has a worse prognosis compared to cutaneous melanoma. Most of the trials on checkpoint inhibitors and targeted therapy have not excluded patients with vulvar melanoma and the preliminary evidence is reviewed in the manuscript. Surgery remains the primary treatment modality of locally resectable vulvar cancer. In view of the rarity, the procedure should be performed in dedicated cancer centers to achieve optimal disease control and maintain continence and sexual function whenever possible.
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http://dx.doi.org/10.1111/ddg.13995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972795PMC
December 2019

Malignant Melanoma of the Vulva and Vagina: A US Population-Based Study of 1863 Patients.

Am J Clin Dermatol 2020 Apr;21(2):285-295

Division of Gynecologic Oncology, Department of Surgical Oncology, University Health Network, Toronto, ON, Canada.

Background: Vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of malignant melanomas with important differences in biology and treatment.

Objective: The objective of this study was to describe the epidemiology and prognosis of VuM and VaM in a large representative cohort.

Methods: Women with invasive VuM or VaM were identified from the Surveillance, Epidemiology and End Results-18 population representing 27.8% of the US population. Data on age, ethnicity, stage, location, histopathology, primary surgery, and lymphadenectomy were collected. The Kaplan-Meier method was used to analyze disease-specific and overall survival. Univariate and multivariate regression models were used to identify factors with a significant association with disease-specific survival.

Results: A total of 1400 VuM and 463 VaM were included for further analysis; 78.6% and 49.7% of women with VuM and VaM underwent surgery, but only 52.9% of women with non-metastatic VuM and 42.9% of women with non-metastatic VaM undergoing surgery had lymph node assessment; one third of these had positive nodes. Superficial spreading was the most common subtype in VuM, and nodular melanoma in VaM (p < 0.001). The median disease-specific survival was 99 months (95% confidence interval 60-138) and 19 months (95% confidence interval 16-22), respectively. Survival was significantly associated with age at diagnosis, ethnicity, stage, surgery, lymph node metastases, histologic subtype, ulceration, mitotic count, and tumor thickness in VuM, and stage, surgery, and lymph node involvement in VaM. In the Cox model, lymph node status and number of mitoses remained independent predictors of outcome in VuM; in VaM, only lymph node status remained significant.

Conclusions: The overall prognosis of VuM and VaM remains poor. The American Joint Committee on Cancer staging system is applicable and should be used for VuM; however, lymph node status and mitotic rate are the most important predictors of survival. Lymph node status should be assessed and patients with positive nodes may be candidates for adjuvant treatment.
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http://dx.doi.org/10.1007/s40257-019-00487-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125071PMC
April 2020

Clinical Monitoring of Sacrococcygeal Teratoma.

Fetal Diagn Ther 2019 20;46(5):333-340. Epub 2019 Mar 20.

The Fetal Center, Children's Memorial Hermann Hospital and the Department of Obstetrics and Gynecology, McGovern Medical School, UTHealth, Houston, Texas, USA.

Background: Sacrococcygeal teratomas (SCT) are often highly vascularized and may result in high-output cardiac failure, polyhydramnios, fetal hydrops, and demise. Delivery is guided by the SCT to fetus volume ratio (SCTratio), SCT growth rate, and cardiac output indexed for weight (CCOi).

Methods: We compared measurements and outcome in 12 consecutive fetuses referred with SCT. Adverse outcomes were: fetal surgery, delivery < 32 gestational weeks or neonatal demise. Only SCTratio and CCOi were used to manage the cases. SCT vascularization index (VI%) was derived from the 3D virtual organ computer-aided analysis (VOCAL) software. The SCTModel (modified from acardiac twins) calculated a hypothetical SCT draining vein size and derived a risk line, using diameters of the superior and inferior vena cava, the azygous and umbilical veins. VI% and a model of systemic and umbilical venous volumes (SCTModel) were tested as indicators for outcome in SCT.

Results: Fetuses were monitored from 20.1 to 36.4 gestational weeks and 5/12 had adverse outcomes: 1 had successful open fetal surgery at 23.8 weeks and delivered at term, 4 delivered at < 32 weeks with 3/4 having neonatal demise between 25 and 29 weeks. VI% was significantly higher in cases with adverse outcomes (mean 10.3 [8.9-11.6] vs. 4.4 [3.4-5.3], p < 0.0001). The additional fraction of the fetal cardiac output required to perfuse the SCT-draining vein (XSCO%) (p = 0.46), SCTratio (p = 0.08), and CCOi (p = 0.64) were not significant. All cases with adverse outcome had VI% > 8%. The SCTModel risk line predicted nonadverse outcomes well but lacked data in 2/5 cases with adverse outcomes.

Conclusions: VI% is a significant indicator of SCT cases with adverse outcomes and combined with SCTratio may guide timing of delivery better than current measures.
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http://dx.doi.org/10.1159/000496841DOI Listing
April 2020

Placental anastomoses in a spontaneous monochorionic-triamniotic triplet pregnancy.

Am J Obstet Gynecol 2019 09 23;221(3):280. Epub 2019 Jan 23.

Department of Obstetrics and Gynecology, Paracelsus Medical University, Salzburg, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2019.01.207DOI Listing
September 2019

Ultrasound Markers in Fetal Hydronephrosis to Predict Postnatal Surgery.

Ultraschall Med 2020 Jun 5;41(3):278-285. Epub 2018 Jul 5.

Obstetrics and Gynecology, Paracelsus Medical University, Salzburg, Austria.

Purpose:  Parents confronted with the finding of antenatal hydronephrosis (ANH) are particularly interested in whether their baby will need postnatal surgery. The objective of this study was to predict ANH requiring surgery on the basis of the fetal anteroposterior renal pelvic diameter (APRPD) and the Society for Fetal Urology (SFU) grading system.

Materials And Methods:  The medical records of 179 patients with the finding of ANH were reviewed retrospectively. ANH was graded according to the SFU grading system. Prenatal ultrasound examinations were correlated to postnatal outcome, which was divided into three groups: prenatal resolution, conservative management and surgical treatment.

Results:  58 (32.4 %) cases were classified as prenatal resolution, 89 (49.7 %) babies were assigned to the conservative outcome group and 32 (17.9 %) patients needed surgical repair. Postnatal surgery was best predicted in the second trimester (area under the receiver operating characteristics curve: 0.839) by an APRPD cut-off of 8.3 mm (sensitivity: 77.8 %; specificity: 85.7 %; PPV of 53.9 %, NPV of 94.7 %). The combination of the parameters "progression of SFU grade" and SFU grade 3 or 4 achieved a sensitivity of 84.4 % and a specificity of 80.3 % for the prediction of surgery.

Conclusion:  Second-trimester APRPD is a useful parameter for predicting the risk for postnatal surgery. The SFU grade should be assessed in every prenatal ultrasound examination as some further risk estimates can be made based on its dynamics over time.
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http://dx.doi.org/10.1055/a-0591-3303DOI Listing
June 2020

The Influence of Blood Pressure on Fetal Aortic Distensibility: An Animal Validation Study.

Fetal Diagn Ther 2018 12;43(3):226-230. Epub 2017 Jul 12.

The Fetal Center, UTHealth McGovern Medical School, Houston, TX, USA.

Background/aims: Aortic distension waveforms describe the change in diameter or cross-sectional area over the cardiac cycle. We aimed to validate the association of aortic fractional area change (AFAC) with blood pressure (BP) in a fetal lamb model.

Methods: Four pregnant ewes underwent open fetal surgery under general anesthesia at 107-120 gestational days. A 4-Fr catheter was introduced into the fetal femoral artery and vein, or the carotid artery and jugular vein. The thoracic aorta was imaged using real-time ultrasound; AFAC was calculated using offline speckle tracking software. Measurements of invasive BP and AFAC were obtained simultaneously and averaged over 10 cardiac cycles. BP was increased by norepinephrine infusion and the association of aortic distensibility with BP was assessed.

Results: Baseline measurements were obtained from 4 lambs, and changes in aortic distensibility with increasing BP were recorded from 3 of them. A positive correlation was found between AFAC and systolic BP (r = 0.692, p = 0.001), diastolic BP (r = 0.647, p = 0.004), mean BP (r = 0.692, p = 0.001), and BP amplitude (r = 0.558, p = 0.016) controlled for heart rate. No association was found between BP and maximum or minimum aortic area.

Conclusion: AFAC provides a quantifiable measure of aortic distensibility and correlates with systolic BP, diastolic BP, mean BP, and BP amplitude in a fetal lamb model.
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http://dx.doi.org/10.1159/000477396DOI Listing
September 2018

Recipient umbilical artery elongation (redundancy) in twin-twin transfusion syndrome.

Am J Obstet Gynecol 2017 08 25;217(2):206.e1-206.e11. Epub 2017 Apr 25.

Fetal Center, Children's Memorial Hermann Hospital, Department of Obstetrics and Gynecology, McGovern Medical School, UTHealth, University of Texas Health Science Center at Houston, Houston, TX. Electronic address:

Background: Chronic hypertension in adults causes arterial lengthening in major arteries, but the effects of early fetal hypertension on the twin-twin transfusion syndrome recipient's vascular architecture remains unknown.

Objective: We hypothesize that arterial cord redundancy is related to recipient hypertension and subsequent heart failure. Our objectives were to: (1) establish a 3-dimensional color Doppler ultrasound method of measuring umbilical arterial length relative to its corresponding venous segment in the umbilical cord using artery vein angle; (2) compare recipient artery vein angle to gestational age-matched controls; and (3) test the association of artery vein angle with recipient heart failure.

Study Design: We compared 3 groups prospectively: twin-twin transfusion syndrome pregnancies undergoing fetoscopic laser surgery (preoperatively) and 2 groups of gestational age-matched controls: uncomplicated monochorionic-diamniotic twin pregnancies and healthy singletons. Using a 3-dimensional color-Doppler volume image of 5 cm of cord near the placental insertion, we traced the umbilical artery and vein producing umbilical artery:vein length, (artery vein index) and measured the artery vein angle between umbilical artery and vein. Correlation of artery vein angle to twin-twin transfusion syndrome stage, maximum vertical pocket, umbilical arterial indices, ductus venosus Doppler, and brain natriuretic peptide were performed. We used pulsed-wave and tissue Doppler to measure tissue Doppler velocities and indexed cardiac output and correlated these with artery vein angle. Comparative statistics, including multivariable linear regression, examined the relationship between umbilical arterial Doppler indices and artery vein angle.

Results: Artery vein angle and artery vein index correlated significantly (R, 0.86; P < .0001), hence, artery vein angle was used for analysis. Mean artery vein angle was 33.1 ± 31.5 degrees in recipients (n = 44), 9.5 ± 6 degrees in monochorionic-diamniotic (n = 11; 22 fetuses), and 8.9 ± 8.3 degrees in singleton controls (n = 16) (P < .001). An artery vein angle ≥26 degrees (>95th percentile for controls) was measured in 52% recipients. Artery vein angle was higher in twin-twin transfusion syndrome stage 3R vs 1 (P = .001). Artery vein angle increased with increasing umbilical arterial pulsatility index (P < .001), and decreased with increasing resistance index (P = .02) after adjusting for gestational age. Interrater agreements to categorize abnormal artery vein angle values was 95% (P < .001). Abnormal ductus venosus Doppler and elevated recipient amniotic fluid N-terminal pro-brain natriuretic peptide/protein levels correlated significantly with artery vein angle. Abnormal artery vein angles were associated with decreased indexed cardiac output, lower tissue Doppler velocities, higher right-sided Tei indices, and severe tricuspid regurgitation.

Conclusion: Umbilical arterial lengthening occurs in 52% of recipients and is associated with abnormal Doppler flows, low systolic tissue Doppler velocities, reduced cardiac output, and elevated markers of cardiac failure. This may reflect chronicity and severity of hypertension in the recipient fetus. Further research is needed to explore the mechanisms of elongation and long-term implications.
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http://dx.doi.org/10.1016/j.ajog.2017.04.024DOI Listing
August 2017

Granulomatous Mycosis Fungoides in an Adolescent-A Rare Encounter and Review of the Literature.

Pediatr Dermatol 2016 Sep;33(5):e296-8

Department of Dermatology, MD Anderson Cancer Center, University of Texas, Houston, TX.

Granulomatous mycosis fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by an infiltrate of atypical lymphocytes, histiocytes, and multinucleated giant cells. Clinically, GMF has a slowly progressing course with a worse prognosis than other forms of MF. With its peak incidence being in the fifth to sixth decade, GMF is rare in children and adolescents. Herein we describe a 14-year-old boy with GMF.
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http://dx.doi.org/10.1111/pde.12959DOI Listing
September 2016

Lymphomatoid Papulosis in Children and Adolescents: A Systematic Review.

Am J Clin Dermatol 2016 Aug;17(4):319-27

Department of Dermatology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4095, USA.

Background: Lymphomatoid papulosis (LyP) is a lymphoproliferative disorder that is rare among adults and even rarer among children. In adults, LyP is associated with an increased risk of secondary lymphomas.

Objective: The aim of this systematic review was to describe the clinical and histopathological features of LyP in children, to assess the risk of associated lymphomas, and to compare the disease to the adult form.

Methods: A systematic review was conducted using the MEDLINE (PubMed), EMBASE, Scopus, and Cochrane databases from inception to June 2015. Articles were included if data were extractable from studies, case series, and single reports of pediatric LyP patients.

Results: A total of 251 children and adolescents with LyP were identified, with the mean age at diagnosis being 9.3 ± 4.6 years (n = 187). The female to male ratio was 1:1.4, and the majority of children reported on were Caucasian (n = 74, 85.1 %). The predominant histologic subtype was type A (n = 106, 79.1 %). Clinically, LyP lesions presented as erythematous papules or nodules, appearing preferentially on the extremities and the trunk. LyP has to be differentiated from pityriasis lichenoides (PL) and primary cutaneous anaplastic large cell lymphoma (ALCL). PL and associated lymphomas were diagnosed before, with, and after LyP in 19 and 14 cases, respectively. Of the 14 subjects with associated lymphomas, two children developed systemic ALCL.

Conclusion: LyP has to be differentiated from ALCL to avoid erroneous treatments. Due to the increased risk of development of non-Hodgkin lymphomas, lifelong follow-up and proper patient counseling are warranted.
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http://dx.doi.org/10.1007/s40257-016-0192-6DOI Listing
August 2016

Fetal cardiovascular hemodynamics in twin-twin transfusion syndrome.

Acta Obstet Gynecol Scand 2016 06 15;95(6):664-71. Epub 2016 Mar 15.

Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Twin-twin transfusion syndrome (TTTS) complicates 10-15% of monochorionic-diamniotic (MCDA) pregnancies. It originates from unbalanced transfer of fluid and vasoactive mediators from one twin to its co-twin via placental anastomoses. This results in hypovolemia in the donor and hypervolemia and vasoconstriction in the recipient twin. Consequently, the recipient demonstrates cardiovascular alterations including atrioventricular valve regurgitation, diastolic dysfunction, and pulmonary stenosis/atresia that do not necessarily correlate with Quintero-stages. Selective fetoscopic laser photocoagulation of placental vascular anastomoses disrupts the underlying pathophysiology and usually improves cardiovascular function in the recipient with normalization of systolic and diastolic function within weeks after treatment. Postnatal studies have demonstrated early decreased arterial distensibility in ex-donor twins, but 10-year follow up is encouraging with survivors showing normal cardiovascular function after TTTS. However, prediction and appropriate early management of TTTS remain poor. Assessment of the cardiovascular system provides additional insight into the pathophysiology and severity of TTTS and may permit more targeted early surveillance of MCDA pregnancies in future. It should form an integral part of the diagnostic algorithm.
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http://dx.doi.org/10.1111/aogs.12871DOI Listing
June 2016

Atrial Function after the Atrial Switch Operation for Transposition of the Great Arteries: Comparison with Arterial Switch and Normals by Cardiovascular Magnetic Resonance.

Congenit Heart Dis 2016 Sep 18;11(5):426-436. Epub 2015 Dec 18.

Division of Cardiology, Pediatric Heart Center, University Children's Hospital Zurich, Zurich, Switzerland.

Objectives: The atria serve as reservoir, conduit, and active pump for ventricular filling. The performance of the atrial baffles after atrial switch repair for transposition of the great arteries may be abnormal and impact the function of the systemic right ventricle. We sought to assess atrial function in patients after atrial repair in comparison to patients after arterial switch repair (ASO) and to controls.

Methods: Using magnetic resonance imaging, atrial volumes and functional parameters were measured in 17 patients after atrial switch repair, 9 patients after ASO and 10 healthy subjects.

Results: After the atrial switch operation, the maximum volume of the pulmonary venous atrium was significantly enlarged, but not of the systemic venous atrium. In both patients groups, independently from the surgical technique used, the minimum atrial volumes were elevated, which resulted in a decreased total empting fraction compared with controls (P < .01). The passive empting volume was diminished for right atrium, but elevated for left atrium after atrial switch and normal for left atrium after ASO; however, the passive empting fraction was diminished for both right atrium and left atrium after both operations (P < .01). The active empting volume was the most affected parameter in both atria and both groups and active empting fractions were highly significantly reduced compared with controls.

Conclusion: Atrial function is abnormal in all patients, after atrial switch and ASO repair. The cyclic volume changes, that is, atrial filling and empting, are reduced when compared with normal subjects. Thus, the atria have lost part of their capacity to convert continuous venous flow into a pulsatile ventricular filling. The function of the pulmonary venous atrium, acting as preload for the systemic right ventricle, after atrial switch is altered the most.
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http://dx.doi.org/10.1111/chd.12323DOI Listing
September 2016

Cutaneous manifestations in trisomy 13 mosaicism: A rare case and review of the literature.

Am J Med Genet A 2015 Oct 5;167A(10):2294-9. Epub 2015 May 5.

Department of Obstetrics and Gynecology, Paracelsus Medical University, Salzburg, Austria.

Trisomy 13 mosaicism is a rare genetic disorder affecting a small minority of all trisomy 13 cases. It occurs when two cell populations that are karyotypically different are present in the same individual and are derived from a single zygote. As a rule, the phenotype is mitigated to a less dysmorphic appearance and longer survival, making genetic counseling a difficult task. Capillary hemangiomas are a common feature of full trisomy 13, seen in 27-56% of all cases. We report on an 18-months-old girl with extensive cutaneous anomalies, mild dysmorphic features, and slight psychomotor delay, without structural defects and provide an up-to-date review of all cases of trisomy 13 mosaicism with skin involvement. To our knowledge, this is the second clinical report of a patient with trisomy 13 mosaicism with hemangiomas and port wine stains, but no structural defects. © 2015 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ajmg.a.37145DOI Listing
October 2015

Early fish oil supplementation and organ failure in patients with septic shock from abdominal infections: a propensity-matched cohort study.

JPEN J Parenter Enteral Nutr 2010 Jul-Aug;34(4):431-7

Department of Anaesthesiology and Critical Care Medicine, Krankenhaus der Barmherzigen Schwestern, Ried im Innkreis, Austria.

Background: Fish oil (FO) has immunomodulating effects and may improve organ function and outcome in critically ill patients. This retrospective, propensity-matched cohort study investigates the effects of early intravenous FO supplementation on organ failure in patients with septic shock from abdominal infection.

Methods: A medical database was retrospectively searched for critically ill patients admitted because of septic shock from abdominal infection (n = 194). Demographic, clinical, and laboratory data; FO supplementation (10 g/d) (n = 42); rate, degree, and number of organ failures assessed by the Sequential Organ Failure Assessment (SOFA) score; and secondary outcome variables were recorded. A propensity score-based model was used to establish 2 comparable groups (FO, n = 29; control, n = 29). Mann-Whitney rank sum test, Fisher exact test, and logistic regression analyses were used to compare variables between groups.

Results: There were no differences in the rate of single organ failures, the maximum SOFA score (median [interquartile range (IQR)], 12 [8-15] vs 11 [9-14]; P = .99), or the number of organ failures (median [IQR], 2 [1-3] vs 2 [1-3]; P = .54] between patients receiving FO supplementation and those not receiving supplementation. There were no group differences in the maximum C-reactive protein levels (P = .1), duration of mechanical ventilation (P = .65) or hemofiltration (P = .21), intensive care unit-acquired infections, intensive care unit length of stay (P = .59), and intensive care unit (P = 1) or hospital mortality (P = 1).

Conclusions: Early intravenous FO may not decrease the number and degree of organ failures in patients with septic shock from abdominal infection. Future trials are needed before FO supplementation in septic shock from abdominal infection can be recommended.
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http://dx.doi.org/10.1177/0148607110362764DOI Listing
January 2011

The association between body-mass index and patient outcome in septic shock: a retrospective cohort study.

Wien Klin Wochenschr 2010 Jan;122(1-2):31-6

Department of Anesthesiology and Critical Care Medicine, Krankenhaus der Barmherzigen Schwestern, Ried im Innkreis, Austria.

Background: It is unknown whether body-mass index (BMI) and commonly defined BMI categories are associated with mortality in patients with septic shock.

Methods: The database of a multidisciplinary intensive care unit (ICU) was retrospectively screened for adult patients with septic shock. BMI, demographic, clinical and laboratory variables together with outcome measures were collected in all patients. Subjects were categorized as follows: underweight, BMI < 18.5; normal weight, BMI 18.5-24.9; overweight, BMI 25-29.9; obesity, BMI >or= 30. Bivariate and multivariate logistic regression models were used to evaluate the association between BMI and outcome parameters.

Results: In total, 301 patients with septic shock were identified. BMI was bivariately associated with ICU mortality (OR 0.91; 95% CI 0.86-0.98; P = 0.007). There was no significant association between BMI and ICU mortality in the multivariate model but an increasing BMI tended to be associated with lower ICU mortality (OR 0.93; 95% CI 0.86-1.01; P = 0.09). Although overweight (OR 0.43; 95% CI 0.19-0.98; P = 0.04) and obese (OR 0.28; 95% CI 0.08-0.93; P = 0.04) patients had an independently lower risk of ICU death than those with normal weight, there was no difference in the risk of ICU death between normal weight and underweight patients (P = 0.22). A high BMI was independently associated with a lower frequency of acute delirium (P = 0.04) and a lower need for ICU re-admission (P = 0.001) but with a higher rate of ICU-acquired urinary tract infections (P = 0.02).

Conclusions: BMI up to 50 does not appear to be associated with worse ICU and hospital mortality in patients with septic shock. In contrast, a high BMI may reduce the risk of death from septic shock.
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http://dx.doi.org/10.1007/s00508-009-1241-4DOI Listing
January 2010

How to protect the heart in septic shock: a hypothesis on the pathophysiology and treatment of septic heart failure.

Med Hypotheses 2010 Mar 3;74(3):460-5. Epub 2009 Nov 3.

Department of Anaesthesiology and Critical Care Medicine, Innsbruck Medical University, Innsbruck, Austria.

Heart failure is a well-recognized manifestation of organ failure in sepsis and septic shock. The pathophysiology of septic heart failure is complex and currently believed to involve several mechanisms. So far, the contributory role of high plasma catecholamine levels has not been investigated. In this manuscript, we present a hypothesis suggesting that excessive catecholamine production and exogenous administration of catecholamines may relevantly contribute to the development of heart failure and cardiovascular collapse in patients suffering from septic shock. Substantially elevated plasma catecholamine levels were measured during critical illness and sepsis or septic shock. There is a growing body of clinical and experimental evidence demonstrating that high catecholamine plasma levels exert direct toxic effects on the heart. The pathophysiologic mechanisms involved in catecholamine-induced cardiomyocyte toxicity may involve a combination of inflammation, oxidative stress, and abnormal calcium handling resulting in myocardial stunning, apoptosis and necrosis. Clinical signs of catecholamine-induced heart failure can present with a wide range of symptoms reaching from subtle histological changes with preserved myocardial pump function to severe heart failure exhibiting a distinctive echocardiographic pattern which became known as "Takotsubo"-like cardiomyopathy or the left ventricular apical ballooning syndrome. In a medical intensive care unit patient population, presence of sepsis was the only variable associated with the development of left ventricular apical ballooning. Since several therapeutic interventions influence catecholamine plasma levels in septic shock patients, treatment strategies aiming at the reduction of endogenous or exogenous catecholamine exposure may protect the heart during septic shock and could facilitate patient survival.
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http://dx.doi.org/10.1016/j.mehy.2009.10.012DOI Listing
March 2010
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