Long-range air dispersion of Candida auris in a cardiothoracic unit outbreak in Hong Kong.

BACKGROUND: Nosocomial outbreaks of Candida auris, a multidrug-resistant fungus, are increasingly reported worldwide; the mode of transmission has usually been reported to be via direct contact. Some studies previously suggested potential short-distance air dispersal during high-turbulence activities, but evidence on long-range air dispersal remains scarce. AIM: To describe a C. auris nosocomial outbreak involving two wards (H7, 5E) in two local hospitals. METHODS: Samples were taken from patients, ward surfaces (frequently touched items and non-reachable surfaces) while settle plates were used for passive air sampling to investigate possible contributions by direct contact and air dispersal. Epidemiological and phylogenetic analyses were also performed on the C. auris isolates from this outbreak. FINDINGS: Eighteen patients were confirmed to have asymptomatic C. auris skin colonization. C. auris was expectedly identified in samplings from frequently touched ward items but was also isolated in two samples from ceiling supply air grilles which were 2.4 m high and inaccessible by patients. Moreover, one sample from a corridor return air grille as far as 9.8 m away from the C. auris cohort area was also positive. Two passive air samplings were positive, including one from a cubicle with no confirmed cases for four days, suggesting possible air dispersal of C. auris. Whole-genome sequencing confirmed clonality of air, environment, and patients' isolates. CONCLUSION: This is the first study to demonstrate potential long-range air dispersal of C. auris in an open-cubicle ward setting. Ventilation precautions and decontamination of out-of-reach high-level surfaces should be considered in C. auris outbreak management.

[GnRH-a combined fertility-sparing re-treatment in women with endometrial carcinoma or atypical endomertial hyperplasia who failed to oral progestin therapy].

Objective: To analyze the clinical efficacy and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based fertility-sparing re-treatment in women with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) who failed with oral progestin therapy. Methods: Forty cases with EC or AEH who failed to respond to oral progestin were included from January 2012 to December 2020 at Peking Union Medical College Hospital. Combination of GnRH-a with levonorgestrel-releasing intrauterine system (group GLI: a subcutaneous injection of GnRH-a every 4 weeks and LNG-IUS insertion constantly) or the combination of GnRH-a with aromatase inhibitor (group GAI: a subcutaneous injection of GnRH-a every 4 weeks and oral letrozole 2.5 mg, daily) were used for these patients. Histological evaluation were performed at the end of each course (every 3-4 months) by hysteroscopy and curettage. After the complete remission (CR), all patients were followed up regularly. Results: (1) Clinical characteristics:among the 40 patients with EC or AEH, the median age at diagnosis was 31 years (range: 22-40 years) and the median body mass index was 24.7 kg/m2 (range: 18.9-39.5 kg/m2). (2) Efficacy of fertility-sparing re-treatment: 37 (92%, 37/40) patients achieved CR, 6 (6/7) in AEH and 31 (94%, 31/33) in EC patients. The CR rate was 93% (26/28) and 11/12 in group GLI and GAI, respectively. The median time to CR was 5 months (range: 3-12 months). At the end of the first therapy course, the CR rates in AEH and EC were 5/7 and 42% (14/33), at the second course, the CR rates were 6/7 and 82% (27/33), respectively. (3) Recurrence: after 25 months of median follow-up duration (range: 10-75 months), 8 (22%, 8/37) women developed recurrence, 1/6 in AEH and 7 (23%, 7/31) in EC patients, with the median recurrence time of 18 months (range: 9-26 months). Among them, two cases who had completed childbirth chose to receive hysterectomy directly. Six patients met the criteria of fertility-preserving therapy and received conservative treatment again and 5 (5/6) of them achieved CR. (4) Pregnancy: of the 37 patients with CR, 33 desired to conceive. Ten women attempted to get pregnancy spontaneously and 23 cases with assisted reproductive technology. Fourteen (42%, 14/33) patients became pregnant, including 9 (27%, 9/33) live births, 3 (9%, 3/33) missed abortions, and 2 (6%, 2/33) miscarriages at the second trimester. Conclusions: GnRH-a based fertility-sparing re-treatment in AEH or EC patients who failed with oral progestin therapy achieved good treatment effect and reproductive outcomes. It is an encouraging alternative regime for patients who failed with oral progestin therapy.

[Imaging features and clinical analysis of diffuse uterine leiomyomatosis cases].

Objective: To discuss the imaging, clinical features and management of diffuse uterine leiomyomatosis (DUL). Methods: Six cases of DUL confirmed in Peking Union Medical College Hospital from August 2009 to September 2019 were reviewed on their image and clinical data. Retrospective analysis was conducted on their perioperative and postoperative follow-up data. Results: The average age of the first diagnosis of DUL was (27±3) years old. All of the patients complained menorrhagia and three patients suffered moderate to severe anemia. Three patients were diagnosed infertility. Pelvic ultrasound and MRI showed symmetrical enlarged uterus with complete replacement of the myometrium by innumerable, confluent leiomyomas.Four patients were treated with GnRH-a before operation to reduce the volume of myoma and correct anemia. Among the six patients, five had undergone myomectomy because of DUL before visiting Peking Union Medical College Hospital. Three patients underwent open myomectomy. The number of resected myoma was 188-300 and the bleeding volume was 1 200-2 500 ml. Two of them suffered recurrence at 51 and 40 months after operation. One received sirolimus for 20 months without recurrence until now. Other three patients underwent hysterectomy. One patient underwent partial small bowel resection and partial omentum resection because of severe pelvic adhesion during hysterectomy, and the blood loss was 2 000 ml. Conclusions: Pelvic imaging especially MRI is helpful for early recognition and preoperative evaluation for DUL. Fertility preservation is a great challenge for DUL patients. The risk of recurrence after myomectomy is high. Hysterectomy is the last choice to completely cure DUL at present.

[Clinicopathological features and prognosis of patients in endometrial cancer with bone metastases].

Objective: To analyze the clinicopathological features and prognosis of patients in endometrial cancer with bone metastases. Methods: A retrospective review of medical records was performed to analyze patients with endometrial cancer who developed bone metastases at Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017, including patients with bone metastases at the diagnosis of endometrial cancer and at recurrence of endometrial cancer. The patient's clinicopathological features, bone metastasis characteristics, treatment process and prognoses were also analyzed. Results: The incidence of bone metastasis of endometrial cancer in PUMCH from 2004 to 2017 was 0.57% (14/2 458). (1) General clinical pathological features: the median age of the 7 patients with bone metastases diagnosed at the time of initial diagnosis was 50 years old, and the main pathological type was endometrioid carcinoma (n=5). The median age of the other 7 patients was 57 years old, with no significant difference comparing to the former groups (P=0.559). (2) The majority site of bone metastasis in endometrial cancer were discovered in pelvic bones, followed by the tibia. (3) Treatment: according to the staging of endometrial cancer, a comprehensive treatment based on surgery was performed, and one patient with isolated bone metastases underwent resection of bone metastasis. (4) Prognosis: nine out of the 14 patients died during the follow-up period. The median over all survival time was 25.5 months (range: 7.7-258.0 months). The median survival of population after diagnosis of bone metastases was 15.0 months (range: 3.0-51.0 months). The survival rate of endometrial cancer at 1-year after diagnosis of bone metastasis was 71.4%. The 2-year survival rate was 40.8%. (5) No independent prognostic factors affecting survival was found (P>0.05). Conclusions: The incidence of bone metastasis in endometrial cancer is less than 1%. Bone metastasis could occur at the diagnosis of endometrial cancer or recurrence of endometrial cancer. Bone metastasis suggests a poor prognosis. There is no standard follow-up and treatment protocols so that individualized treatment is needed.

[Analysis of clinical characters of female vulvar Paget disease].

Objective: To investigate the clinical and pathological features, diagnosis and treatment of primary vulvar Paget disease (VPD) , and analyze the related factors that may affect the recurrence. Methods: A retrospective study was carried out on 36 patients diagnosed as VPD pathologically from January 1983 to December 2017 at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. The clinical and pathological features, diagnosis, treatment and prognosis and the factors influencing recurrence rate of VPD were analyzed. Results: (1) Totally 94% (34/36) of VPD occurred in postmenopausal women. Pruritus was counted 86% (31/36) of the main complaint. Lesions of vulvar were main symptom which had no specificity, acting as ulcer (67%, 24/36) , erythema (50%, 18/36) , depigmentation (42%, 15/36) , sclerosis (31%, 11/36) , and pigmentation (17%, 6/36) . The lesions invaded labium majus (97%, 35/36) , sometimes labium minus (53%, 19/36) , clitoris (28%, 10/36) , perianal (25%, 9/36) , orificium vaginae (3%, 1/36) , and meatus urinarius (3%, 1/36) . Approximately 19% (7/36) of VPD coexisted with intraepithelial neoplasia or adenocarcinoma of vulvar or other part of body. (2) Diagnosis and treatment: diagnosis was confirmed histologically by biopsy or pathologies after surgery, and immunohistochemical results were helpful for differential diagnosis. Surgery was the mean treatment method, 34 of all the 36 patients (94%, 34/36) underwent surgery for at least once, while 2 patients (6%, 2/36) were performed non-operative treatment. The surgical treatment included excision of focus, wide local excision, simple vulvectomy, and extensive vulvectomy. The non-operative treatment included radiotherapy, chemotherapy, laser, photodynamic therapy, and so on. (3) Prognosis: among 36 VPD patients, 4 were lost to follow-up with a 89% (32/36) follow-up rate. Median follow-up was 35.3 months (range,1 month to 31 years) . During the follow-up period, 2 patients were unable to judge whether they will relapse for the follow-up time did not reach half a year, 8 cases were unsuccessful operation, 20 cases succeeded, the achievement ratio was 71% (20/28) . Nine of twenty cases relapsed, the recurrence rate was 45% (9/20) . The median recurrence time was 14 months after operation. One patient of the 32 followed-up patients died, the mortality rate was 3% (1/32) . (4) The related factors affected the recurrence of VPD: t test was applied to the analysis of patients' age, rank test was used in the statistics of the time of confirmed diagnosis, the length and thickness of the resection focus. Fisher test was used to calculate whether the focus were limited to the epidermis, type of surgical procedures, distance between the margin and the focus, whether tumor cells infiltrated the margin. The results showed that none of the above terms in the first operation had significant contribution to recurrence (all P>0.05) . Conclusions: VPD may be a low potential malignancy, which could slowly progress into deep invasive disease. VPD is often associated with intraepithelial neoplasia or primary tumors of the vulva or somewhere else. Operations is the first choice for VPD, but consider for its high recurrence rate after operation, close follow-up should be strongly suggested.

Enhanced Cd2+ -selective root-tonoplast-transport in tobaccos expressing Arabidopsis cation exchangers.

Several Arabidopsis CAtion eXchangers (CAXs) encode tonoplast-localized transporters that appear to be major contributors to vacuolar accumulation/sequestration of cadmium (Cd(2+)), an undesirable pollutant ion that occurs in man largely as a result of dietary consumption of aerial tissues of food plants. But, ion-selectivity of individual CAX transporter types remains largely unknown. Here, we transformed Nicotiana tabacum with several CAX genes driven by the Cauliflower Mosaic Virus (CaMV) 35S promoter and monitored divalent cation transport in root-tonoplast vesicles from these plants in order to select particular CAX genes directing high Cd(2+) antiporter activity in root tonoplast. Comparison of seven different CAX genes indicated that all transported Cd(2+), Ca(2+), Zn(2+), and Mn(2+) to varying degrees, but that CAX4 and CAX2 had high Cd(2+) transport and selectivity in tonoplast vesicles. CAX4 driven by the CaMV 35S and FS3 [figwort mosaic virus (FMV)] promoters increased the magnitude and initial rate of Cd(2+)/H(+) exchange in root-tonoplast vesicles. Ion selectivity of transport in root-tonoplast vesicles isolated from FS3::CAX4-expressing plant lines having a range of gene expression was Cd(2+)>Zn(2+)>>Ca(2+)>>Mn(2+) and the ratios of maximal Cd(2+) (and Zn(2+)) versus maximal Ca(2+) and Mn(2+) transport were correlated with the levels of CAX4 expression. Root Cd accumulation in high CAX4 and CAX2 expressing lines was increased in seedlings grown with 0.02 muM Cd. These observations are consistent with a model in which expression of an Arabidopsis-gene-encoded, Cd(2+)-efficient antiporter in host plant roots results in greater root vacuole Cd(2+) transport activity, increased root Cd accumulation, and a shift in overall root tonoplast ion transport selectivity towards higher Cd(2+) selectivity. Results support a model in which certain CAX antiporters are somewhat more selective for particular divalent cations.

Structural determinants of Ca2+ transport in the Arabidopsis H+/Ca2+ antiporter CAX1.

Ca(2+) levels in plants, fungi, and bacteria are controlled in part by H(+)/Ca(2+) exchangers; however, the relationship between primary sequence and biological activity of these transporters has not been reported. The Arabidopsis H(+)/cation exchangers, CAX1 and CAX2, were identified by their ability to suppress yeast mutants defective in vacuolar Ca(2+) transport. CAX1 has a much higher capacity for Ca(2+) transport than CAX2. An Arabidopsis thaliana homolog of CAX1, CAX3, is 77% identical (93% similar) and, when expressed in yeast, localized to the vacuole but did not suppress yeast mutants defective in vacuolar Ca(2+) transport. Chimeric constructs and site-directed mutagenesis showed that CAX3 could suppress yeast vacuolar Ca(2+) transport mutants if a nine-amino acid region of CAX1 was inserted into CAX3 (CAX3-9). Biochemical analysis in yeast showed CAX3-9 had 36% of the H(+)/Ca(2+) exchange activity as compared with CAX1; however, CAX3-9 and CAX1 appear to differ in their transport of other ions. Exchanging the nine-amino acid region of CAX1 into CAX2 doubled yeast vacuolar Ca(2+) transport but did not appear to alter the transport of other ions. This nine-amino acid region is highly variable among the plant CAX-like transporters. These findings suggest that this region is involved in CAX-mediated Ca(2+) specificity.

Vascular invasion routes and systemic accumulation patterns of tobacco mosaic virus in Nicotiana benthamiana.

Plant viruses must enter the host vascular system in order to invade the young growing parts of the plant rapidly. Functional entry sites into the leaf vascular system for rapid systemic infection have not been determined for any plant/virus system. Tobacco mosaic virus (TMV) entry into minor, major and transport veins from non-vascular cells of Nicotiana benthamiana in source tissue and its exit from veins in sink tissue was studied using a modified virus expressing green fluorescent protein (GFP). Using a surgical procedure that isolated specific leaf and stem tissues from complicating vascular tissues, we determined that TMV could enter minor, major or transport veins directly from non-vascular cells to produce a systemic infection. TMV first accumulated in abaxial or external phloem-associated cells in major veins and petioles of the inoculated leaf and stems below the inoculated leaf. It also initially accumulated exclusively in internal or adaxial phloem-associated cells in stems above the inoculated leaf and petioles or major veins of sink leaves. This work shows the functional equivalence of vein classes in source leaves for entry of TMV, and the lack of equivalence of vein classes in sink leaves for exit of TMV. Thus, the specialization of major veins for transport rather than loading of photoassimilates in source tissue does not preclude virus entry. During transport, the virus initially accumulates in specific vascular-associated cells, indicating that virus accumulation in this tissue is highly regulated. These findings have important implications for studies on the identification of symplasmic domains and host macromolecule vascular transport.