Attitudes and perceptions of affected women towards endocrine endometriosis therapy: an international survey based on free-word association networks.

STUDY QUESTION: What are the attitudes and perceptions towards endocrine endometriosis therapy? SUMMARY ANSWER: Among the study population, endocrine endometriosis therapies are associated with negative mental images and emotions and there seems to be a pre-therapeutic information deficit on the part of physicians. WHAT IS KNOWN ALREADY: Endocrine therapies, as the current standard of conservative endometriosis treatment, have good efficacy and improve symptoms and quality of life in most patients. Nevertheless, clinical practice repeatedly shows rejection on the part of patients, which may result in reduced compliance and discontinuation of therapy. STUDY DESIGN, SIZE, DURATION: Cross-sectional study among endometriosis patients using a multilingual questionnaire distributed via the most popular social media channels between November 2020 and February 2021. A total of 3348 women participated in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on a pilot phase, an international, multilingual online survey was conducted among women affected by endometriosis. The questionnaire included free-word associations and questions about personal medical history, source of information, and demographic data. Mental representations were detected based on modules of the co-occurrence network of associations. MAIN RESULTS AND THE ROLE OF CHANCE: Six modules with different dominant emotional labels emerged from the confluence of associations to endocrine endometriosis therapy mentioned by participants. Five modules reflected negative mental associations, with the most frequently mentioned words being 'side effects', 'pain', 'ineffective', 'depression', and 'uncertainty'. Of the 12 most frequently selected emotions, only 'optimistic' was positive. Side effects affecting mental health are the most important reason for deciding against endocrine therapy in our survey population. Twenty-seven percent of respondents reported knowing little about endocrine therapies for endometriosis. Social media are the most frequently used sources of information and were rated as the most useful. LIMITATIONS, REASONS FOR CAUTION: By translating the questionnaire, questions might have been understood differently depending on the language. By using social media channels for distribution, digitally literate patients were targeted. The survey population might not be representative as patients who are critical/unhappy with therapy are more likely to seek advice from peer groups. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study replicate the findings of a recent survey in three European countries. Given the prevalence of endometriosis and the few emerging pharmaceutical alternatives, these data point to a growing need for further research and development of non-hormonal drugs for treating endometriosis. Most endometriosis patients are young and digitally literate, and much information is obtained from alternative sources, such as social media. Careful education before starting therapy should be taken seriously, and patients' concerns should be addressed individually by health care providers. This could help reduce misunderstanding and misinformation and improve treatment adherence and satisfaction. STUDY FUNDING/COMPETING INTEREST(S): There is no funding or conflict of interest to declare. TRIAL REGISTRATION NUMBER: The trial is not registered at any trial registry.

Maltreatment during childhood: a risk factor for the development of endometriosis?

STUDY QUESTION: Is maltreatment during childhood (MC), e.g. sexual abuse, physical abuse, emotional abuse and neglect, associated with diagnosis of endometriosis? SUMMARY ANSWER: Childhood sexual abuse, emotional abuse/neglect and inconsistency experiences were associated with the diagnosis of endometriosis while no such association was found for physical abuse/neglect and other forms of maltreatment. WHAT IS KNOWN ALREADY: Symptoms of endometriosis such as chronic pelvic pain, fatigue and depression, are correlated with MC, as are immune reactions linked to endometriosis. These factors support a case for a potential role of MC in the development of endometriosis. STUDY DESIGN, SIZE, DURATION: The study was designed as a multicentre retrospective case-control study. Women with a diagnosis of endometriosis were matched to control women from the same clinic/doctor's office with regard to age (±3 years) and ethnic background. A total of 421 matched pairs were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with endometriosis and control women were recruited in university hospitals, district hospitals, and doctors' offices in Germany, Switzerland and Austria. A German-language version of the Childhood Trauma Questionnaire (CTQ) was used to evaluate MC. Diagnosis of endometriosis was confirmed histologically and classified according to ASRM criteria. MAIN RESULTS AND THE ROLE OF CHANCE: Women with endometriosis reported significantly more often than control women a history of sexual abuse (20%/14%, P = 0.0197), emotional abuse (44%/28%, P < 0.0001), emotional neglect (50%/42%, P = 0.0123) and inconsistency experiences (53%/41%, P = 0.0007). No statistically significant differences could be demonstrated for physical abuse/neglect (31%/26%, P = 0.1738). Combinations of different abuse/neglect experiences were described significantly more often in women with endometriosis. Frequencies of other MC, i.e. violence against the mother (8%/7%, P = 0.8222), drug abuse in the family (5%/3%, P = 0.0943), mentally handicapped family members (1%/1%, P = 0.7271), suicidal intentions in the family (6%/4%, P = 0.2879) and family members in prison (1%/1%, P = 0.1597) were not statistically different in women with endometriosis and control women. LIMITATIONS, REASONS FOR CAUTION: Some control women might present asymptomatic endometriosis, which would lead to underestimation of our findings. The exclusion of pregnant women may have biased the results. Statistical power for sub-analyses of physical abuse/neglect and sexual abuse was limited. WIDER IMPLICATIONS OF THE FINDINGS: A link to MC needs to be considered in women with endometriosis. As there are effective strategies to avoid long-term consequences of MC, healthcare professionals should inquire about such experiences in order to be able to provide treatment for the consequences as early as possible. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Endo_QoL NCT02511626.

[Switching the Treatment Regime from PRN (pro re nata, as needed) to T&E (Treat and Extend) for Intravitreal Therapy with Anti-VEGF Agents in Private Practice or Small Institutions]. / Umstellung des Therapieschemas pro re nata (PRN) auf Treat and Extend (T&E) in der intravitrealen Therapie mit Anti-VEGF-Medikamenten in der Praxis oder kleineren Institutionen.

In everyday practice, intravitreal therapy in an "as needed" regimen (pro re nata, PRN) is less predictable and requires more visits (monitoring and injections taken together) with poorer functional results than with the treat and extend (T&E) regimen. Current literature supports the benefit of a switch. However, practical advice is still missing. This article provides "best practice" recommendations for private practice or smaller institutions for the change from PRN to T&E. The requirements are organisational adjustments, staff training, definition of the scenario triggering the switch (A - functional or anatomical deterioration; B - general switch at a predefined date), counselling of the patients, defining benchmarks for the follow-up of the switch and preparing for higher capacity utilisation during the transition (shorter treatment intervals during the switching phase). Guidance is provided for each phase (a, preparation; b, transition; and c, follow-up).

Indications and long-term clinical outcomes in 282 patients with pelvic exenteration for advanced or recurrent cervical cancer.

OBJECTIVE: The aim of this study was to summarize the clinical experience at our clinic with pelvic exenteration as a treatment for cervical cancer with special regard to the indications and outcomes of specific patient groups. METHODS: Medical records of 282 women who underwent pelvic exenteration to treat cervical cancer were analyzed. RESULTS: In total, 70 patients (25%) underwent primary exenteration, and 212 (75%) underwent secondary exenteration. Exenteration was anterior for 14 (5%) patients, posterior for 6 (2%) and total for 262 (93%). The overall survival (OS) of the 282 patients was 41% at 5 years and 37% at 10 years. The disease-free survival at 5 years was 61%. For 133 patients for whom pelvic exenteration was a curative procedure, the OS was 64% at 5 years and 57% at 10 years. For cases of pelvic exenteration as a palliative intervention, the OS was 19% at 5 years and 18% at 10 years. No difference was seen in the OS at 5 years between patients who received primary and secondary operations. No significant difference in the OS was found regardless of whether the patients had positive pelvic lymph nodes, whereas in cases of paraaortic lymph node metastasis, the OS was significantly lower. Out of all of the procedures, 139 (49%) involved no perioperative or postoperative complications. One major complication was reported for 72 (26%) patients, two complications occurred for 42 patients (15%) and more than three complications were noted for 29 (10%) patients. CONCLUSION: Pelvic exenteration is an effective technique with a high percentage of long-term survivors. To the best of our knowledge, our study involves the largest published number of patients treated with pelvic exenteration for a single gynecological cancer and shows that previous contraindications for pelvic exenteration, such as lymph node metastasis (especially when confined to the pelvic lymph nodes), older age or palliative intent, should be reconsidered.

Inpatient and outpatient loop electrosurgery excision procedure for cervical intraepithelial neoplasia: a retrospective analysis.

PURPOSE: To determine whether the outpatient loop electrosurgical excision procedure (LEEP) conization (out-LEEP) is as effective and safe as inpatient LEEP conization (in-LEEP) with regard to the complete removal of cervical dysplasia, recurrence-free survival and post-operative morbidity. METHODS: 233 patients were included in this retrospective cohort study from January 2002 to December 2007. 181 had outpatient treatment and 52 inpatient treatment. We used Mann-Whitney U test, two-sided Fisher's exact test, Chi-square test, log rank test and Kaplan-Meier curve. RESULTS: Incomplete excision was found in 16/52 (30.8%) cases in the inpatient group and 46/181 (25.4%) in the outpatient group (P = 0.48). Six patients had post-operative complications: two cases of secondary haemorrhage in each group (in-LEEP 3.8%, out-LEEP 1.1%, P = 0.22) and two cases of cervical stenosis amongst inpatients (3.8%, P = 0.049). Alteration of specimen by thermal artifact were reported in 4/52 (7.7%) of in-LEEP cones and 10/181 (5.5%) of out-LEEP cones (P = 0.52). Measurements of cones in both groups were comparable with a mean depth of 9.35 mm (±5.5 mm) and 8.4 mm (±3.4 mm), respectively. CONCLUSION: Our results suggest that efficacy and safety of ambulatory LEEP conization is comparable as in inpatient procedure.

Comparison of quartz vials with polypropylene vials for rapid cryopreservation of human ovarian tissue.

BACKGROUND: Because higher survival of follicles during the freezing/thawing procedure improves the quality of cryopreserved tissue reimplanted after oncological therapies, defining an optimal method for human ovarian tissue cryopreservation remains a major issue in this field. One option to improve the cryopreservation procedure is to use better materials, i.e., vials with better conductivity. The aim of this study was to compare polypropylene (PP) with quartz vials. Between September 2012 and January 2013, eight patients were recruited. The ovarian cortex was cut into 3 slices, assigned randomly to a fresh and a cryopreserved group in PP (method B) or quartz vials (method C). Histological and immunohistochemical (IHC) analysis were used. For IHC three antibodies were analyzed: Ki67 (proliferation index), Bcl2 (anti apoptotic index) and Hsp70 (stress index). RESULTS: The majority of GCs showed positive staining for Bcl2 in both cryopreservation device, with higher expression in group C than in group B. Oocytes and their nuclei showed intense positive staining for ki67 in both methods B and C, and also a patch positive stromal cells staining for Ki67. Expression of hsp70 was not increased after cryopreservation. CONCLUSIONS: Cryopreservation using quartz vials led to larger numbers of good follicles while maintaining consistent preservation for stromal cells and vessels.

[Intermittent diplopia after prolonged downward gaze to the right: what is the differential diagnosis?]. / Diplopie intermittente dans le regard à droite: quels diagnostics possibles?

In general, intermittent diplopia evokes suspicion of ocular myasthenia gravis. However, other etiologies such as Brown syndrome or myokymia of the superior oblique may provoke intermittent diplopia. We present a case of intermittent diplopia due to a tumor in the cavernous sinus. A 59-year-old patient reported intermittent diplopia after prolonged downward gaze to the right. All other gaze directions failed to provoke symptoms. In 1992, the diagnosis of inactive macroadenoma of the pituitary gland was established and the patient underwent surgery and radiation therapy. At physical examination, prolonged downward gaze to the right of about 2 minutes provoked paresis of abduction, slight ptosis, and restriction of elevation on the left side, corresponding to sixth nerve palsy and palsy of the superior branch of the third nerve on the left side. MRI showed a relapse of the macroadenoma with infiltration of the cavernous sinus on the left side. The patient underwent surgery then focal radiation (gamma-knife). The clinical course was favourable and at the follow-up examination six months later, no diplopia was reported.

[Persistent visual problems thirty years after severe head trauma]. / Problèmes de vision persistant trente ans après un traumatisme crânien.

INTRODUCTION: Visual disturbances are common after severe head trauma. Some authors report 50 percent of these patients having damage to the visual system, ocular motor nerve palsies, or central eye movement disturbances. Visual disturbances influence prognosis and outcome of neurological rehabilitation, and, in most cases, diagnosis and treatment require interdisciplinary care. CASE REPORT: We report here a 50-year-old patient who suffered from severe head trauma at age 20. After coming out of a 4-week coma, he suffered visual disturbances such as blurred vision and diplopia. Visual acuity was 1.0 and the visual fields were intact. The symptoms remained unexplained for a long time. One year after the trauma, right trochlear palsy was diagnosed and surgical treatment was performed. However, the symptoms persisted, and one year later, a second operation was performed without changing the symptoms. During many years, prisms or refractive corrections were used to improve the visual disturbances, and finally, a psychiatric treatment was started. At age 40, the patient became presbyopic and his visual problems increased, especially for reading. When he was examined for the first time in our consultation, corrected visual acuity was 1.0 with a small hyperphoria of the right eye. During careful examination of the eye downgaze, a conjugate pure torsional nystagmus was observed, which disappeared in primary gaze position. CONCLUSION: Pure torsional nystagmus is difficult to diagnose, especially when it is provoked only by one gaze direction such as in our patient. As a sequel of the severe head trauma with brainstem contusion, this type of nystagmus is a rare form of central vestibular nystagmus, and may by modified by head rotation or suppressed by convergence. The "treatment" of the patient's blurred vision when reading was easy by ordering goggles with a near part placed near the primary gaze position and a 6 base down prismatic correction. Reading was then possible without provoking torsional nystagmus.

Primary orbital Ewing sarcoma in a middle-aged woman.

A 43-year-old woman had unilateral exophthalmos caused by primary orbital Ewing sarcoma. Specialized immunohistochemical stains, primarily MIC-2 (CD99), aided in the diagnosis of Ewing sarcoma. Twenty-two months after radiotherapy and multiagent chemotherapy, the patient remained tumor free. To our knowledge, this is the first reported case of orbital Ewing sarcoma to present in an adult beyond the fourth decade of life.

Melanocytes and iris color. Electron microscopic findings.

OBJECTIVE: To quantitatively associate iris color with melanocyte pigment content. METHODS: Autopsy eyes were classified as uniform-blue, uniform-hazel, or uniform-brown or showing a darker peripupillary ring. Using electron microscopic images and computerized image analysis, area, number, and size of mature melanosomes within the perinuclear cytoplasmic area only or within perinuclear and peripheral cytoplasmic areas of the superficial stromal melanocytes combined were measured. RESULTS: Average melanosomal area per perinuclear cytoplasmic area (AMAC) and average number of melanosomes per perinuclear area (AMNC) significantly differed across iris color groups (overall P<.001). This result reflects the large difference between blue-uniform and all other color groups. A marginally significant (nominal) trend from blue-ring through brown-ring was also detected (P=.06 for AMAC and P=.07 for AMNC). The average perinuclear cytoplasmic area was larger in the central iris zone (within 1 mm around the pupillary margin) than in the intermediate iris zone (between 1 and 2 mm around the pupillary margin) (P=.002), but AMAC and AMNC did not significantly differ between zones. The average melanosome size did not differ significantly across color groups (P=.11). CONCLUSION: Differences in iris colors are at least partially attributed to variable AMNC and AMAC within superficial melanocytes.

The color of the human eye: a review of morphologic correlates and of some conditions that affect iridial pigmentation.

Iris color can be affected by a variety of ocular disorders. It is suspected that iris color may not remain constant throughout life. These observations have drawn attention to the morphologic correlates of iris color and its regulation. Differences in the iris color of normal eyes are the result of variable amounts of melanin pigment granules within a constant number of melanocytes in the superficial stroma of the iris. These melanocytes seem to reach their genetically determined amount of melanin in early childhood, and their melanin content usually remains constant in adulthood. Diseases such as Horner's syndrome and Fuchs' heterochromic iridocyclitis affect iris color, resulting in a decrease of iris pigmentation. Evidence suggests that melanin content of some melanocytes is subject to adrenergic regulation even past childhood. Application of the prostaglandin analogue latanoprost, on the other hand, leads to an increase in iris pigmentation in some patients. Studies with cultured dermal and uveal melanocytes, as well as with uveal melanoma cells, however, show no increase in cell proliferation when treated with latanoprost in vitro. The mechanisms by which latanoprost affects regulation of iris pigmentation requires further investigation.

Cost-effectiveness of trastuzumab in the adjuvant treatment of early breast cancer: a model-based analysis of the HERA and FinHer trial.

BACKGROUND: Routine adjuvant administration of trastuzumab (T) has been implemented in most centers, but its economic impact has not yet been well examined. METHODS: A Markov model was constructed based on clinical data of the Herceptin Adjuvant (HERA) and the Finland Herceptin (FinHer) trials. Costs from the perspective of a Swiss health care provider were calculated based on resource use. RESULTS: On the basis of HERA data, our model yielded an overall survival rate of 71.8% for the T group versus 62.8% for the control group [risk ratio (RR) = 0.87) after 10 years and 62.9% versus 52.7% (RR = 0.84) after 15 years. Cost-effectiveness resulted in 40505 Euros (EUR) per life years gained (LYG) after 10 years and 19673 EUR per LYG after 15 years. For the FinHer regimen, overall survival after 10 and 15 years resulted in 81.8% versus 66.1% (RR = 0.81) and 73.6% versus 57.0% (RR = 0.77). Costs of 8497 EUR per patient could be saved after 10 years and 9256 EUR after 15 years compared with the control group. CONCLUSION: In a long-term perspective, adjuvant T based on the HERA regimen can be considered cost-effective. The regimen used in the FinHer trial is even cost saving, but estimations are based on a single small trial.

Clinicopathologic correlation of intraretinal microvascular abnormalities.

PURPOSE: To define the cross-sectional morphology of intraretinal microvascular abnormalities, which previously have been described only in terms of trypsin digestion. MATERIAL/METHODS: Fourteen vascular lesions of five patients with diabetic retinopathy were identified on fundus photographs and/or fluorescein angiograms and classified as intraretinal microvascular abnormalities. Eyes of these patients were obtained after the patients' deaths. The period between the time at which the photographs were taken and that at which enucleation was performed was 3-20 months. The duration of autolysis before fixation was 5 hours or less. The embedded tissue was evaluated by light and electron microscopy, and these findings were correlated with the clinical appearance. RESULTS: The lesions consisted of multiple, closely spaced, thin-walled vascular lumina with a caliber of 20-70 microns. They were located in the inner retina and surrounded by a wide cuff containing randomly oriented collagen fibers. Endothelial cell nuclei were numerous. Pericyte degeneration and multiplication of the endothelial and pericyte basement membrane had occurred. Endothelial junctions were short, and gaping of junctions was not seen. However, occasional fenestrations were present. CONCLUSION: The cross-sectional morphology of intraretinal microvascular abnormalities is consistent with vascular pathology typical for intraretinal diabetic microangiopathy, but also includes features usually seen in new vessels. This supports the concept that intraretinal microvascular abnormalities have the particular potential for neovascularization.

Evaluation of a peptidomimetic ribonucleotide reductase inhibitor with a murine model of herpes simplex virus type 1 ocular disease.

The ribonucleotide reductase (RR) of herpes simplex virus type 1 (HSV-1) is an important virulence factor, being required for neurovirulence, ocular virulence, and reactivation from latency. The RR activity requires the association of two distinct homodimeric subunits, and the association of the subunits is inhibited in the presence of a peptide homologous to the carboxy terminus of the small subunit. A structural analog of the inhibitory peptide (BILD 1263) has been shown to inhibit the replication of HSV-1 at micromolar concentrations in vitro. We used a mouse model of HSV-1 ocular infection to determine the in vivo efficacy of topical BILD 1263. Treatment of HSV-1 KOS-infected mice resulted in significant reductions in the severity and incidence of stromal keratitis and corneal neovascularization. At higher concentrations (5%) BILD 1263 reduced the severity but not the incidence of blepharitis. Treatment with 5% BILD 1263 also reduced viral shedding from the cornea by 10- to 14-fold (P < 0.001). In uninfected mice treated with 5% BILD 1263, we found no evidence of corneal epithelial damage, conjunctivitis, or blepharitis, and histopathological studies revealed no changes in the corneas of these mice. These results show that the peptidomimetic RR inhibitor BILD 1263 is effective in preventing disease, has an antiviral effect in vivo, and has little or no toxicity.

[Varicella zoster virus and atypical necrotizing retinopathies in HIV and AIDS patients]. / Varicella-Zoster-Virus und atypische nekrotisierende Retinopathien bei HIV- und AIDS-Patienten.

BACKGROUND: Necrotizing retinopathies of suspected viral origin, but which do not meet the criteria for either CMV-retinitis or acute retinal necrosis syndrome, have been grouped together under the term atypical necrotizing retinopathies. Nothing is known about their etiology. PATIENTS AND METHODS: Aqueous humor samples were drawn from two HIV-positive and eight patients with AIDS presenting with an atypical necrotizing retinopathy, additionally from six patients with acute retinal necrosis syndrome and 28 patients with active CMV-retinitis at the time of diagnosis as well as from thirty healthy controls at surgery. All samples underwent DNA extraction and amplification for viral DNA of HSV-1, VZV and CMV. RESULTS: VZV-DNA was detected in seven of nine aqueous humor samples derived from patients with atypical necrotizing retinopathies and in four of six samples from patients with acute retinal necrosis syndrome, but not in any one from the 28 patients with CMV retinitis. In the latter group, CMV DNA was detectable in 23 samples, in two of these additionally HSV-1 DNA. No viral DNA was amplified from any of the samples from healthy controls. CONCLUSIONS: Varicella zoster virus ist the leading cause of atypical necrotizing retinopathies. This should be considered in the antiviral chemotherapy. Moreover, we were able to establish the diagnosis using DNA amplification for the viruses of the herpes family irrespective of the etiology in 80% of necrotizing retinopathies.

The herpes simplex virus type 1 ribonucleotide reductase is required for acute retinal disease.

We have used a herpes simplex virus type 1 (HSV-1) ribonucleotide reductase (RR) null mutant (ICP6 delta) to determine if the HSV-1 RR is required for acute retinal disease. Injection of the ICP6 delta mutant into the vitreous induced mild transient signs of infection (vitreal infiltrate, retinal inflammation, and changes in retinal cytology). In contrast, the parental KOS and a revertant virus (ICP6 delta + 3.1) in which the RR gene had been restored, caused severe retinitis. Injection of media alone also induced mild transient signs of disease. Two months after infection, ICP6 delta injected eyes could not be distinguished from normal eyes. Repeated injection of ICP6 delta (3 times, 2 weeks apart) resulted in vitreal infiltrate near the site of injection but the retina did not appear damaged. The mutant, ICP6 delta, grew to peak titers 1 x 10(3) to 1 x 10(5)-fold lower and cleared faster than KOS or ICP6 delta + 3.1 in the injected eyes suggesting that the reduced virulence was due to reduced ability of the virus to grow. These results show that the viral RR is required for acute retinal disease.

Treatment of spontaneously arising retinoblastoma tumors in transgenic mice with an attenuated herpes simplex virus mutant.

The use of viruses to treat tumors has received renewed interest with the availability of genetically defined attenuated mutants. Herpes simplex virus (HSV) type 1 in particular has been shown to be effective for tumors of neuronal origin. However, the model systems used for these studies rely on the use of explanted tumor cells in immunodeficient animals. We have used a recently developed transgenic mouse model, wherein mice spontaneously develop retinoblastomas, to determine if a mutant HSV has a therapeutic effect against an endogenously arising tumor in an immunocompetent host. The injection of 1 x 10(6) PFU of the neuroattenuated HSV-1/HSV-2 recombinant RE6 into the vitreous of transgenic mice resulted in a significant inhibition of tumor growth compared to injection of medium alone (P = 0.0063). Immunohistochemical analysis of viral antigen showed that viral replication was restricted to focal areas of the tumors and the retinal pigment epithelium. Viral growth was not significantly different in the eyes of transgene-positive and transgene-negative mice, suggesting that enhanced replication in tumor cells may not explain the effects. Tumor cells in the treated eyes were significantly less differentiated than those in the untreated eyes (P = 0.04), suggesting that the virus may replicate better in certain cell types in the tumors. Although the injection of RE6 resulted in a difference in tumor size, the treatment did not result in the elimination of tumors in any of the mice improvements in the efficacy of tumor control are needed if this therapy is to be of use.