Randomized phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer.

OBJECTIVE: Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. The aim was to establish the role of nintedanib in addition to paclitaxel and carboplatin in first-line recurrent/metastatic cervical cancer. METHODS: Double-blind phase II randomized study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin-paclitaxel with oral nintedanib 200 mg BID/placebo. The primary endpoint was progression-free survival (PFS) at 1.5 years and α = 0.15, ß = 80%, one sided. RESULTS: 120 patients (62 N, 58C) were randomized. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favor of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However, N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Global health status during and at the end of the study was similar in both arms. CONCLUSION: The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.

Conservative management of abnormally invasive placenta complicated by local hyperfibrinolysis and beginning disseminated intravascular coagulation.

INTRODUCTION: Abnormally invasive placenta (AIP) is often associated with high maternal morbidity. In surgical treatment, caesarean hysterectomy or partial uterine resection may lead to high perioperative maternal blood loss. A conservative treatment by leaving the placenta in utero after caesarean delivery of the baby is an option to preserve fertility and to reduce peripartum hysterectomy-related morbidity. Nevertheless, due to increased placental coagulation activity as well as consumption of clotting factors, a disseminated intravascular coagulation (DIC)-like state with secondary late postpartum bleeding can occur. PURPOSE: Systematic review after the presentation of a case of conservative management of placenta percreta with secondary partial uterine wall resection due to vaginal bleeding, complicated by local hyperfibrinolysis and consecutive systemic decrease in fibrinogen levels. METHODS: Systematic PubMed database search was done until August 2019 without any restriction of publication date or journal RESULTS: Among 58 publications, a total of 11 reported on DIC-like symptoms in the conservative management of AIP, in the median on day 59 postpartum. In most cases, emergency hysterectomy was performed, which led to an almost immediate normalization of coagulation status but was accompanied with high maternal blood loss. In two cases, fertility-preserving conservative management could be continued after successful medical therapy. CONCLUSION: Based on these results, we suggest routinely monitoring of the coagulation parameters next to signs of infection in the postpartum check-ups during conservative management of AIP. Postpartum tranexamic acid oral dosage should be discussed when fibrinogen levels are decreasing and D-Dimers are increasing.

A GCIG international survey: clinical practice patterns of sentinel lymph node biopsies in cervical cancer.

PURPOSE: To evaluate the practice patterns among centers and physicians worldwide regarding sentinel lymph node biopsies (SLNB) in cervical cancer (CC) patients. METHOD: A validated 35-item questionnaire regarding SLNB in CC supported by the Gynecologic Cancer Intergroup (GCIG), and sponsored by the North-Eastern German Society of Gynaecologic-Oncology (NOGGO) was sent to all major gynecological cancer societies across the globe for further distribution from October 2015 and continued for a period of 7 months. RESULTS: One hundred and sixty-one institutions from around the world participated. One hundred and six (66%) of the participants were from university centers and 111 (69%) were gynecologic oncologists. One hundred and fifty-two (97%) performed lymphadenectomy (LNE) and 147 (94%) did so systematically; 97 (60%) used SLNB, due to lower morbidity (73%), reliability (55%) and time-saving (27%). In cases of positive SLNB (pN+), 39% of respondents stopped the operation and sent the patient for chemoradiation (CRT), 45% completed pelvic and paraaortic LNE, whereas 26% went on to perform a radical hysterectomy (RH) and systematic pelvic and paraaortic LNE. In case of negative SLNB (pN0), 39% of institutions still performed a systematic pelvic and paraaortic LNE. CONCLUSION: In this survey worldwide, SLNB adoption is an encouraging 60%, yet ample differences exist regarding strategy, and to a lower extent the techniques used. Lack of experience is the most common reason SLNB is not performed. Efforts to increase surgical education on SLNB technique and multicenter prospective trials providing evidence-based guidelines are warranted.

Laparoscopic radical hysterectomy in cervical cancer as total mesometrial resection (L-TMMR): a multicentric experience.

OBJECTIVE: To analyze the feasibility of total mesometrial resection by laparoscopy (L-TMMR) in a multicentric series of early stage cervical cancer. METHOD: We prospectively evaluated a consecutive series of cervical cancer patients with pre-operative FIGO stages IA2-IB1 at the Catholic University in Rome and in Campobasso and the Charitè University in Berlin. All cases were assessed at pre-operative MRI scan and clinically confirmed by investigation under anesthesia, adhering strictly to the FIGO criteria. The surgical and post-surgical data were collected. RESULTS: 104 women with cervical cancer were admitted between July 2013 and August 2014 and among them 71 patients with pre-operative FIGO stages IA2-IB1 were treated with L-TMMR. One laparotomic conversion was registered. The median operative time was 260min (120-670min), estimated blood loss was 100cm(3) (25-900cm(3)), and the median length of hospital stay was 6days (2-26days). We observed 8 intra-operative complications including a vascular injury of the left internal iliac vein that caused conversion, 6 vesical injuries and 1 ureteral injury managed laparoscopically. Two vescico-vaginal fistula and one hemoperitoneum were observed as major post-operative complications (4.2%). CONCLUSION: L-TMMR can be safely performed in selected cervical cancer patients. Further larger prospective trials are needed to evaluate the oncological outcome of patients undergoing this surgical procedure.

Nail toxicity related to taxanes.

A 70-year-old woman with non-small-cell lung cancer developed severe nail toxicity while she was being treated with docetaxel at three-week intervals. Docetaxel is a chemotherapeutic agent of the taxane family. Taxanes are well known to cause nail changes, but mainly when used on a weekly basis.

Pattern of spontaneous breathing: potential marker for weaning outcome. Spontaneous breathing pattern and weaning from mechanical ventilation.

OBJECTIVE: To quantitatively assess the spontaneous breathing (SB) pattern, during minimal ventilatory support, of patients who pass or fail weaning trials from mechanical ventilation. DESIGN: A prospective, clinical trial. SETTING: Intensive care unit of a university teaching hospital. PATIENTS: Fifty-two tracheally intubated and hemodynamically stable patients who were judged clinically ready for extubation. METHODS: Using a computerized respiratory profile monitor, continuous respiratory parameters were obtained while patients were receiving four or less synchronized intermittent mandatory (SIMV) breaths and during CPAP trials. Coefficients of variation (CV) of spontaneous tidal volumes and flows during SIMV trials as well as the entropies and dimensions of the breathing patterns during CPAP trials were used to assess the dynamical breathing behaviors of the patients who passed or failed weaning trials. MEASUREMENTS AND RESULTS: Thirty-nine extubations were successful and 13 were not. The CV of the spontaneous tidal volumes (VT) and the spontaneous peak inspiratory flows (PF), the Kolmogorov entropy and the dimension of the SB patterns were compared in the two groups. The CV of VT (9.13 +/- 4.11 vs 26.07 +/- 6.94), the CV of PF (11.63 +/- 4.18 vs 29.88 +/- 12.07), the Kolmogorov entropy (0.09 +/- 0.03 bits/cycle vs 0.39 +/- 0.09 bits/cycle), and the dimension of the SB pattern (1.33 +/- 0.07 vs 3.93 +/- 0.47) were all significantly smaller (P < 0.05) in the successfully extubated group versus the group that failed extubation. CONCLUSION: The spontaneous breathing pattern during minimal mechanical ventilatory support is more chaotic in patients who failed extubation trials compared to patients who passed extubation trials. Thus, we speculate that characterizing the SB pattern during minimal ventilatory support might be a useful tool in differentiating between extubation success and failure.

A new cut-off point of thyromental distance for prediction of difficult airway.

BACKGROUND: Difficult intubation, often unexpected, remains a primary concern for the anesthesiologist. None of the bedside tests have proven to be efficacious and highly predictive. The prupose of this study was to correlate the full range of thyromental distance with both the Cormack grade and the Mallampati score. METHODS: One hundred and sixty patients undergoing general anesthesia were included in the study. Patients with abnormal atlanto-occipital extension, small chin size and mouth opening were excluded from the study. The thyromental distance, the Mallampati score, and the Cormack grade were determined in all patients. The correlation between the thyromental distance and each of the Cormack grade and the Mallampati score was determined, as well as the correlation between the Mallampati score and the Cormack grade. The cut-off value of the tyromental distance that discriminated best between patients with easy glottic visualization (Cormack grade 1,2) vs. difficult visualization (Cormack grade 3,4) was derived. RESULTS: A significant and high correlation was observed between the thyromental distance and the Cormack grade (r = -0.72). In contrast, a lower correlation was observed between the thyromental distance and the Mallampati score (r = -0.41) and the Mallampati score and the Cormack grade (r = 0.47). A cut-off value for the TMD of 4 cm was the best in discriminating between patients with difficult and easy glottic visualization. The combination of TMD < or = 4 cm and Mallampati score of 3,4 predicted the patients with the most difficult glottic visualization. CONCLUSION: Patients with a thyromental distance greater than 4 cm can be easily intubated. In contrast, when the TMD < or = 4 cm, tracheal intubation is difficult in 48% of patients if the Mallampati score is 1,2 and in 79% if the Mallampati score is 3 or 4.

Recurrent anterior uveitis and glaucoma associated with inadvertent entry of ointment into the anterior chamber after radial keratotomy.

Anterior uveitis and elevated intraocular pressure (IOP) occurred after radial keratotomy that was complicated by microperforation and penetration of antibiotic ophthalmic ointment into the anterior chamber. Anterior uveitis and IOP elevation were observed during the early postoperative follow-up and 41 and 61 months after surgery. All 3 attacks responded well to topical anti-inflammatory and antiglaucoma treatment. The probable causes of the uveitis and glaucoma in this case are discussed.

Modification of an anesthesia machine for MRI suite.

The modification of a wall mounted anesthesia machine, rendering it nonmagnetic for use in the magnetic resonance imaging suite, is described. The modified anesthesia machine functioned properly at 1.8 m distance from 1.5 tesla electromagnet without degrading its imaging.

Double T-piece, an injector, and Bird ventilator use in MRI suite.

The double T-piece breathing system is described. The Bird Ventilator Mark 2 is utilised as an oxygen pressure jet to drive an injector placed at the distal end of the double T-piece breathing system. An active anti-pollution assembly is employed. Both the double T-piece breathing system and the anti-pollution assembly are valveless. The injector's design is described. The ventilator functioned properly at 1.8 m distance from 1.5 tesla electromagnet without degrading its imaging. The Bird ventilator, the injector, and the double T-piece breathing system are small in size, easy to handle, and can be used for paediatric and adult patients.

Topical use of zinc desferrioxamine for corneal alkali injury in a rabbit model.

PURPOSE: To evaluate the efficacy of topical zinc desferrioxamine in acute corneal alkali injury in rabbits. METHODS: Twenty rabbits were anesthetized and a standardized alkali burn (1N NaOH) was performed in the center of the cornea (7.5-mm diameter). The animals were randomly divided into two groups and treated (double-masked) with topical zinc desferrioxamine, 220 microM, (group 1) or its vehicle (group 2). Drops were applied 7 times/day for 28 days. Topical gentamicin, 0.3%, was instilled twice a day. Animals were evaluated twice a week. At each examination (using the slit-lamp), the depth of corneal ulcer was graded as follows: 0, no ulcer; 1, tissue loss less than one third of corneal thickness; 2, one third to two thirds tissue loss; 3, more than two thirds tissue loss; 4, descemetocele; or 5, perforation. Ulceration area, vascularization, and epithelial defects also were measured. RESULTS: During the study period, the grading of mean corneal ulcerations in group 1 ranged from 0.2 to 1.00, whereas in group 2, it ranged from 1.4 to 2.7. The mean grade and area of ulceration in group 2 were greater than those in group 1 (p < 0.05). CONCLUSION: Topical zinc desferrioxamine may be an adjunctive treatment in protecting the cornea against induced alkali injury.

Reduction of pneumococcal nasopharyngeal carriage in early infancy after immunization with tetravalent pneumococcal vaccines conjugated to either tetanus toxoid or diphtheria toxoid.

BACKGROUND: Pneumococcal nasopharyngeal colonization is important for transmission of the organisms. We assessed the ability of two tetravalent conjugate vaccines administered in early infancy to prevent carriage of vaccine-related pneumococci. METHODS: A vaccine containing pneumococcal type 6B, 14, 19F and 23F polysaccharide conjugated to tetanus toxoid (Pnc-T) and a vaccine containing the same four polysaccharides conjugated to diphtheria toxoid (Pnc-D) were compared with placebo, in a double blinded study (25 infants per group). Vaccines (or placebo) were injected at 2, 4 and 6 months of age. At 12 months of age a native (nonconjugate) polysaccharide vaccine was administered as a booster. Serum type-specific anticapsular antibody concentrations were measured and nasopharyngeal cultures were obtained at 2, 4, 6, 7, 12 and 13 months of age. RESULTS: In general carriage of all pneumococci (vaccine- and non-vaccine-related) was low at age 2 months and increased with age. However, for the vaccine-related serotypes (6A, 6B, 14, 19F and 23F) carriage was not increased with age in Pnc-D or Pnc-T recipients. Of all cultures obtained after the full primary series, 7 of 72 (10%), 3 of 62 (5%) and 19 or 70 (27%) were positive for the vaccine-related pneumococcal serotypes among the Pnc-D, Pnc-T and placebo recipients, respectively (P = 0.001 for Pnc-D vs. placebo; P = 0.014 for Pnc-T vs. placebo). Most of the antibiotic-resistant isolates belonged to the vaccine-related serotypes. CONCLUSIONS: A significant reduction in the carriage of vaccine-related strains after administration of conjugate vaccines was observed. These preliminary results suggest that transmission of specific pneumococcal serotypes most often associated with disease and antibiotic resistance may at least partially be controlled by immunization.

[Airbag-associated ocular trauma].

Airbags have received widespread recognition as an effective means of enhancing automobile safety. They are particularly effective in frontal and front angle collisions which otherwise would be fatal or cause serious injuries. Inflation of the bag helps protect the driver and front-seat-passenger from hitting the steering wheel, dashboard or windshield. In frontal crashes airbags have reduced driver deaths, hospital admission rates, and incidence of brain injury. On the other hand, an increasing variety of airbag-associated organ injuries has been reported, including blunt ocular and chemical trauma, 2 cases of ocular trauma due to airbags which resulted in choroidal rupture with disastrous outcome in terms of visual acuity are presented. Since the very first report in May 1991 of airbag-associated ocular trauma until June 1996, there has apparently been only 1 case of choroidal rupture due to airbag-associated trauma, presented in 1 sentence of a brief report. Although airbag-related eye trauma may be relatively infrequent, the severity of the injuries incurred, especially when the posterior segment of the eye was involved, warrants research on new airbag design that minimizes the risk of ocular injury. Meanwhile all cases of airbag-associated ocular trauma should be reported, so that medical staff, the general population and car manufacturers will become more aware of this medical issue.

Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine.

Children 12-18 months old were randomized to receive one dose of a conjugate heptavalent pneumococcal vaccine, two doses of the same vaccine, or one dose of a 23-valent native polysaccharide vaccine. Before immunization, pneumococci included in the conjugate vaccine were isolated from 24% of the children, and an antibiotic-resistant pneumococcus was isolated from 22% of the children. The vaccines had no effect on carriage of non-vaccine-type pneumococci. In contrast, there was a significant reduction in carriage of vaccine-type pneumococci 3 months after one dose and 1 month after a second dose of conjugate vaccine (from 25% to 9% and 7%, respectively; P < .001). No effect was seen after vaccination with the nonconjugate vaccine. One year after immunization, carriage of antibiotic-resistant vaccine-type pneumococci in children receiving conjugate vaccine was lower than that in children receiving the nonconjugate vaccine (4% vs. 14%, P = .042). Conjugate pneumococcal vaccines may reduce spread of pneumococci in the community.