Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein–Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV− PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199–1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751–6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077–0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.     

Distinct immunopathological mechanisms of EBV-positive and EBV-negative posttransplant lymphoproliferative disorders

EBV-positive and EBV-negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, we conducted a multicentric prospective study with 56 EBV-positive and 39 EBV-negative PTLD patients of the K-VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD-free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK- and T cell phenotypes (n = 49 and 94), and performed EBV-specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot-IFNγ assays (n = 50). EBV-negative PTLD patients, NK cells overexpressed Tim-3; the 2-year progression-free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4⁺<300 cells/mm³, p <  .001). EBV-positive PTLD patients presented a profound NK-cell lymphopenia (median = 60 cells/mm³) and a high proportion of NK cells expressing PD-1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV-specific T cells of EBV-positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N-terminal portion of EBNA-3A viral protein. Altogether, this broad comparison of EBV-positive and EBV-negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.     

Ovarian tissue grafting: Lessons learnt from our experience with 55 grafts

Purpose

Uncertainties remain regarding the clinical efficacy of ovarian tissue cryopreservation and grafting. We report a retrospective analysis of reproductive outcomes and lessons learnt following 55 ovarian tissue transplant procedures at our center from 2006 to 2019.

Methods

We analyzed variables related to graft success such as tissue volume, follicular density, total follicular volume, and age on the duration of graft function.

Results

Follicular density and total follicular volume correlate positively with duration of graft function. All clinical pregnancies in our cohort occurred in women who were aged 35 or less at the time of ovarian tissue cryopreservation.

Conclusion

Graft success, as determined by eventual pregnancy and the longevity of graft function, may be impacted by factors including age at cryopreservation, follicular density, and total follicular volume.

     

弧菌,气单胞菌及邻单胞菌编码鉴定研究

采用编码技术对医学常见的弧菌属、气单胞菌属及邻单胞菌属的１２ 个菌种进行编码,建立了７ 位数编码鉴定法。并用此法鉴定了２０８ 株标准菌株,与常规鉴定法比较,两法无显著统计学意义（χ２ ＝０－４４ ,Ｐ＞０－０５）,符合率为９５－６７％ 。此鉴定法快捷、可靠、操作简便、判定结果简单、适合于临床、卫生及基层微生物实验室推广应用。     

Single neurons are differently involved in stimulus-specific oscillations in cat visual cortex

Synchronised oscillatory population events (35–80 Hz; 60–300 ms) can be induced in the visual cortex of cats by specific visual stimulation. The oscillatory events are most prominent in local slow wave field potentials (LFP) and multiple unit spikes (MUA). We investigated how and when single cortical neurons are involved in such oscillatory population events. Simultaneous recordings of single cell spikes, LFP and MUA were made with up to seven microelectrodes. Three states of single cell participation in oscillations were distinguished in spike triggered averages of LFP or MUA from the same electrode: (1) Rhythmic states were characterised by the presence of rhythmicity in single cell spike patterns (35–80 Hz). These rhythms were correlated with LFP and MUA oscillations. (2) Lock-in states lacked rhythmic components in single cell spike patterns, while spikes were phase-coupled with LFP or MUA oscillations. (3) During non-participation states LFP or MUA oscillations were present, but single cell spike trains were neither rhythmic nor phase coupled to these oscillations. Stimulus manipulations (from optimal to suboptimal for the generation of oscillations) often led to systematic transitions between these states (from rhythmic to lock-in to non-participation). Single cell spike coupling was generally associated with negative peaks in LFP oscillations, irrespective of the cortical separation of single cell and population signals (0–6 mm). Our results suggest that oscillatory cortical population activities are not only supported by local and distant neurons with rhythmic spike patterns, but also by those with irregular patterns in which some spikes occur phase-locked to oscillatory events.     

Are radiologists meeting the needs of Australian medical oncologists? Results of a national survey

Although radiological evaluation plays an integral role in the management of oncology patients, little is known about which elements of such evaluation are most important or about how satisfied clinicians are with the quality of radiology services in cancer patients. We have developed a 36‐item anonymous survey evaluating availability of and satisfaction with radiology services to medical oncologists. The survey was distributed to members of the Medical Oncology Group of Australia resident in Australia. We received 124 responses (51%). Most respondents (76.9%) were satisfied with their radiology services. Satisfaction correlated closely with the availability of standardized reporting and promptness of reporting (P < 0.001). Oncologists in private practise were more likely to receive prompt reports (P < 0.0001). Oncologists in public practice were more concerned about availability of CT scanning (P = 0.02). Services that were reported as less frequently available, despite being ranked as very important, included measurements of key lesions and comparison to previous studies. Standardized reporting was considered helpful by 91% of respondents. Only 32.5% of respondents reported receiving such a summary in more than 50% of cases and 21% never received such a summary. Our findings highlight the need for closer collaboration between oncologists and radiologists in order to address specific needs and develop optimal patterns of practise. Consideration should be given to standardization of reporting of radiology studies in oncology.     

临床肿瘤学的现状和展望

由于肿瘤发病率和在居民死亡原因中所占比例越来越高,肿瘤防治一直是各国卫生领域内的重点课题之一。本文对近年来肿瘤预防和治疗的新观点和新资料做了介绍,并指出循证医学、规范化和个体化在新时代的重要性。而在高发区开展研究和通过现代科学方法阐明中医药的作用是对我们民族对世界医学做出贡献的重要途径。     

How to organize gynecologic oncology in the future: Results of an internationalquestionnaire

Vergote IB, de Oliveira CF, Dargent D. How to organize gynecologic oncologyin the future: Results of an international questionnaire. Int J GynecolCancer 1997; 7: 368–375.
A questionnaire was sent to 93 gynecologic oncologists from 54 countriesabout the way in which gynecologic oncology was organized in their country, orif the (sub)speciality wasnot yet recognized, how they thought it should be organized. The questionnairewas answered by 64 persons from 42 different countries. The subspecialty wasrecognised in 17 (41%) of the countries. Fifty-five respondents (86%) thought thatgynecologic oncology should be a subspecialty of obstetrics and gynecology. Themedian duration of the gynecologiconcologic fellowship program was 30 months. Diagnosis and surgery accounted forabout 58% of the duration of the program. In 52% of the answersfrom countries with boardcertification, the fellows had to pass a theoretical and practical examination,and in addition 22% of the candidates had to defend a thesis to qualifyfor certification.Training centers in countries that recognized gynecologic oncology had amedian number of 142 new cases per year (for 1 fellow). The median number ofgynecologic oncologogistsand fellows per 10⁽⁷⁾ inhabitants in countries with boardcertification in gynecologic oncology was 42 and 6, respectively. Finally, theimportant role of internationalsocieties (like the International Gynecologic Cancer Society and the EuropeanSociety of Gynaecological Oncology) in supporting the countries withoutrecognized GynecologicOncology was stressed by the respondents. The setting up of internationalstandards for training programs, training centers, board certification, and theorganization ofinternational exchange programs for fellows seemed to be equally important,according to the questionnaire responses.     

Outbreak of nosocomialAcinetobacter baumannii bacteremia in a high risk ward

Acinetobacter baumannii is emerging as a major cause of nosocomial infections particularly in high risk patients. Being resistant to adverse environmental conditions, it can stay for prolonged periods in the hospital environment. We report an outbreak in the medical oncology ward where nine patients suspected of bacteraemia were blood culture positive forA. baumannii from the two samples each, one collected through the i.v. cannula and another through the peripheral venous puncture. The bacteria was also isolated from the environmental sources from the various samples collected. The biotype, antibiogram, cellular protein profiles on SDS-PAGE and the restriction enzyme analysis patterns of the patient isolates and the environmental isolates were similar. This points to the environment as a source of infection. With reinforcement of proper barrier nursing and use of disposable heparine ampoules it was possible to control the outbreak.     

Ⅰ型疫苗衍生脊髓灰质炎病毒循环的发现和基因特点

目的分析贵州省2004年Ⅰ型循环的疫苗衍生脊髓灰质炎(脊灰)病毒(cVDPVs)的基因特征,阐述cVDPVs的出现为全球消灭脊灰带来的挑战。方法2004年中国疾病预防控制中心(CDC)病毒病预防控制所国家脊灰实验室对各个省送检的每1个脊灰病毒分离株进行聚合酶链反应-限制性酶切片段长度多态性分析(PCR-RFLP)和酶联免疫吸附试验(ELISA)两种方法的型内鉴定。毒株型内鉴别显示异常时,则对该株病毒进行VP1编码区全基因的序列测定和分析。结果2004年从贵州省CDC送检的脊灰病毒株(或粪便标本的复核)中,共发现9株Ⅰ型疫苗衍生脊灰病毒(VDPVs)。这9株VDPVs从2例急性弛缓性麻痹(AFP)病例和4名接触者的粪便标本中分离到。其中8株分离于贞丰县挽兰乡的2例AFP病例和3名接触者,另外1株分离于贞丰县白层镇的1名AFP病例接触者。结论对9株cVDPVs的VP1编码区的序列测定和分析证实,它们有相似的核苷酸序列,共享5个核苷酸突变位点,说明VDPVs已发生了循环。cVDPVs很可能来源于2003年秋季的1次口服脊灰减毒活疫苗病毒的传播。对其中5株VDPVs的3D区和1株VDPV(8229-2)的全序列测定和分析,未发现脊灰病毒血清型之间的重组,也未发现与非脊灰肠道病毒的重组。