Impact of etoposide and ASCT on survival among patients aged <65 years with stage II to IV PTCL: a population-based cohort study.

Patients aged <65 years with peripheral T-cell lymphoma (PTCL) are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Although the addition of etoposide (CHOEP) and consolidation with autologous stem cell transplantation (ASCT) are preferred in some countries, randomized trials are lacking. This nationwide population-based study assessed the impact of etoposide and ASCT on overall survival (OS) among patients aged 18 to 64 years with stage II to IV anaplastic large-cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), or PTCL not otherwise specified (NOS) diagnosed between 1989 and 2018 using the Netherlands Cancer Registry. Patients were categorized into 2 calendar periods, representing pre- and post-eras of etoposide and ASCT, respectively. A total of 1427 patients were identified (ALCL, 35%; AITL, 21%; and PTCL NOS, 44%). OS increased from 39% in the period from 1989 to 2009 to 49% in the period of 2009 to 2018 (P < .01). Five-year OS was superior for patients treated with CHOEP vs CHOP (64% and 44%, respectively; P < .01). When adjusted for subtype, International Prognostic Index score, and ASCT, the risk of mortality was similar between the 2 groups, except for patients with ALK+ ALCL, for whom the risk of mortality was 6.3 times higher when treated with CHOP vs CHOEP. Patients undergoing consolidation with ASCT had superior 5-year OS of 81% compared with 39% for patients not undergoing ASCT (P < .01), regardless of whether complete remission was achieved. In patients aged <65 years with advanced-stage ALK- ALCL, AITL, or PTCL, the use of ASCT consolidation, but not the addition of etoposide, was associated with improved OS.

ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition.

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.

Outcome of combined modality treatment in first-line for stage I(E) peripheral T-cell lymphoma; a nationwide population-based cohort study from the Netherlands.

Peripheral T-cell lymphomas (PTCL) comprise a heterogeneous group of mature T-cell neoplasms with an unfavorable prognosis; presentation with stage I(E) disease is uncommon. In clinical practice, an abbreviated chemotherapy treatment regimen combined with radiotherapy (combined modality treatment [CMT]) is commonly used, although evidence from clinical trials is lacking. The aim of this nationwide population-based cohort study is to describe first-line treatment and outcome of patients with stage I(E) PTCL. All newly diagnosed patients ≥18 years with stage I(E) anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma NOS (PTCL not otherise specified [NOS]) in 1989-2020 were identified in the Netherlands Cancer Registry. Patients were categorized according to treatment regimen, i.e., chemotherapy (CT), radiotherapy (RT), CMT, other therapy and no treatment. The primary endpoint was overall survival (OS). Patients with stage I(E) ALCL, AITL and PTCL NOS (n=576) were most commonly treated with CMT (28%) or CT (29%), 2% underwent SCT. RT only was given in 18%, and 8% received other therapy and 16% no treatment. Overall, the 5-year OS was 59%. According to subtype, 5-year OS was superior for ALCL as compared to PTCL NOS and AITL (68% vs. 55% and 52%, respectively; P=0.03). For patients treated with CMT, 5-year OS was significantly higher (72%) as compared to patients treated with either CT or RT alone (55% and 55%, respectively; P<0.01). In multivariable analysis, age per year increment (hazard ratio [HR] =1.06, 95% confidence interval [CI]: 1.05-1.07), male sex (HR=1.53, 95% CI: 1.23-1.90), and CT, or no treatment (HR=1.64, 95% CI: 1.21-2.21, and HR=1.55, 95% CI: 1.10-2.17, respectively) were associated with a higher risk of mortality. For stage I(E) ALCL, AITL and PTCL NOS, 5-year OS is 59%, comparing favorably to historical outcome in advanced-stage disease. Superior outcome estimates were observed in patients treated with CMT.

[Preliminary observation of wearable balance diagnosis and treatment system in evaluating dynamic and static balance function in patients with vestibular vertigo].

A newly developed wearable balance diagnosis and treatment system was studied to evaluate the indexes of the abnormal balance function in patients with vestibular vertigo. A cross-sectional study was carried out. A total of 30 patients diagnosed with non-acute vestibular vertigo in the outpatient department of Eye, Ear, Nose and Throat Hospital Affiliated to Fudan University from July 2022 to May 2023 were selected as the vertigo group, including 13 males and 17 females, and aged (45.7±13.9) years. Meanwhile, 20 healthy controls (8 males and 12 females) were included as the control group, with a mean age of (43.6±8.0) years. The static balance and limits of stability (LOS) function of all subjects were assessed with wearable balance diagnosis and treatment system developed under the leadership of Eye & ENT Hospital of Fudan University. In the static balance test, the ratio of eyes open with cushions to eyes open without cushions in the vertigo group was less than that of the control group[1.20% (0.92%, 1.53%) vs 1.49% (1.22%, 1.81%), P=0.008], indicating that patients with non-acute vestibular vertigo may compensate static balance ability earlier. In vertigo group, the directional control in 8 directions, the maximum excursion in anterior, posterior, right anterior and right posterior directions, the endpoint excursion in the posterior, right posterior, and left posterior directions were all smaller than those of the control group (all P<0.05). The reaction time in the left posterior direction of vertigo group was longer than that of the control group (all P<0.05). Those results indicated that the directional control, maximum excursion and endpoint excursion of LOS could be considered as important reference indexes for dynamic balance function.

[Analysis of clinical characteristics and risk factors of postoperative complications in infants with early-onset necrotizing enterocolitis after enterostomy].

Objective: To investigate the clinical characteristics of children with early-onset necrotizing enterocolitis (NEC) undergoing enterostomy and analyze the risk factors for postoperative complications. Methods: Retrospective analysis was conducted on the clinical data (perinatal conditions, clinical characteristics, clinical outcomes, etc.) of NEC patients who underwent enterostomy at Beijing Children's Hospital from May 2016 to May 2023. The patients were divided into two groups based on the age of onset: an early-onset enterostomy group (<14 days) and a late-onset enterostomy group (≥14 days). Furthermore, the children with NEC were categorized into complication group and non-complication group based on whether there were complications after enterostomy. The differences in clinical data between these groups were analyzed, and the clinical characteristics of children with early-onset NEC and enterostomy were summarized. Multivariate logistic regression model was employed to analyze the risk factors for postoperative complications in NEC children with enterostomy. Results: A total of 68 cases were enrolled, including 43 cases in the early-onset enterostomy group [26 males and 17 females, aged (6.5±3.0) days] and 25 cases in the late-onset enterostomy group [15 males and 10 females, aged (21.0±3.0) days]. There were 28 cases (17 males and 11 females), age [M (Q1, Q3)] 9 (5, 14) days in the complication group and 33 cases (22 males and 11 females), aged of 14 (6, 21) days in the non-complication group. Compared to the late-onset enterostomy group, the early-onset enterostomy group had significantly higher rates of intraventricular hemorrhage [30.2% (13/43) vs 8.0% (2/25)], hemodynamically significant patent ductus arteriosus [37.2% (16/43) vs 12.0% (3/25)], mechanical ventilation≥72 hours after birth [39.5% (17/43) vs 16.0% (4/25)], stage Ⅲ NEC [(69.8% (30/43) vs 40.0% (10/25)], extensive NEC [27.9% (12/43) vs 8.0% (2/25)], and short-term postoperative complications [56.8% (21/37) vs 29.2% (7/24)] (all P<0.05).Multivariate logistic regression model analysis revealed that residual length of proximal small intestine was a protective factor for postoperative complications after enterostomy in NEC infants (OR=0.764, 95%CI: 0.648-0.901, P=0.001), but stage Ⅲ NEC was a risk factor (OR=1.042, 95%CI: 1.004-5.585, P=0.017). Conclusions: The incidence of postoperative complications is high, and the prognosis is poor in children with early-onset NEC enterostomy. The residual length of proximal enterostomy is a protective factor for postoperative complications of NEC enterostomy, but stage Ⅲ NEC is a risk factor.

[A case of nontuberculous mycobacterium presenting as a mass and atelectasis with mediastinal and hilar lymph node enlargement].

With the development of testing technology, the diagnosis of nontuberculous mycobacterium (NTM) lung disease has gradually increased in recent years. Because the clinical characteristics of NTM are not typical, and its imaging manifestations are diverse and nonspecific, missed diagnosis and misdiagnosis are common. Etiological investigation is necessary for diagnosis. Conventional etiological investigations are very limited for the diagnosis of NTM. We reported a case of NTM lung disease presenting with a mass and atelectasis with mediastinal and hilar lymph node enlargement that resembled malignant tumors. The literature on this condition was reviewed to improve the clinician's understanding and broaden clinical thinking.

Role of immune checkpoint inhibitors in metastatic uveal melanoma: a single-center retrospective cohort study.

BACKGROUND: Uveal melanoma is an orphan malignancy with very limited data on treatment options in metastatic setting. METHODS: In this single-center retrospective study, we describe real-world epidemiological and survival data on 121 metastatic uveal melanoma (MUM) patients registered in our institution. As a large tertiary referral center, almost 30% of all diagnoses in the Flemish region of Belgium were covered. Primarily, we determined whether introduction of immune checkpoint inhibitors (ICI) led to improved overall survival (OS) in MUM patients. Secondarily, response rates to ICI were assessed and we evaluated whether first-line ICI could be a valid alternative to liver-directed therapy (LDT) in liver-only disease. RESULTS: The initially perceived 10.8 months survival benefit from treatment with ICI disappeared after correction for immortality bias. By analyzing treatment type as time-varying covariate on OS, no significant benefit of ICI over other systemic therapies (HR = 0.771) or best supportive care (BSC) (HR = 0.780) was found. Also comparison of the pre-ICI versus ICI era showed no OS improvement after introduction of ICI in our center (p = 0.7994). Only liver-directed and local oligometastatic approaches were associated with a lower chance of mortality when compared to ICI (p = 0.0025), other systemic therapies (p = 0.0001) and BSC (p = 0.0003), yet without correction for selection bias. We reported overall response rates on ICI ranging from 8-15% and we found some support for neoadjuvant strategies with ICI resulting in remission or downsizing, allowing oligometastatic approaches later on. In first-line liver-only disease, median real-world progression-free survival and OS did not significantly differ between patients treated with LDT or ICI upfront (p = 0.2930 and p = 0.5461 respectively). CONCLUSION: Although we documented responses to ICI, our analyses do not demonstrate an OS benefit of ICI over alternative treatment strategies for MUM. However, local treatment options, whether liver-directed or for oligometastatic disease, may be beneficial and should be considered.

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study.

BACKGROUND: Pembrolizumab demonstrated durable antitumor activity in 233 patients with previously treated advanced microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors in the phase II multicohort KEYNOTE-158 (NCT02628067) study. Herein, we report safety and efficacy outcomes with longer follow-up for more patients with previously treated advanced MSI-H/dMMR noncolorectal cancers who were included in cohort K of the KEYNOTE-158 (NCT02628067) study. PATIENTS AND METHODS: Eligible patients with previously treated advanced noncolorectal MSI-H/dMMR solid tumors, measurable disease as per RECIST v1.1, and Eastern Cooperative Oncology Group performance status of 0 or 1 received pembrolizumab 200 mg Q3W for 35 cycles or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) as per RECIST v1.1 by independent central radiologic review. RESULTS: Three hundred and fifty-one patients with various tumor types were enrolled in KEYNOTE-158 cohort K. The most common tumor types were endometrial (22.5%), gastric (14.5%), and small intestine (7.4%). Median time from first dose to database cut-off (5 October 2020) was 37.5 months (range, 0.2-55.6 months). ORR among 321 patients in the efficacy population (patients who received ≥1 dose of pembrolizumab enrolled ≥6 months before the data cut-off date) was 30.8% [95% confidence interval (CI) 25.8% to 36.2%]. Median duration of response was 47.5 months (range, 2.1+ to 51.1+ months; '+' indicates no progressive disease by the time of last disease assessment). Median progression-free survival was 3.5 months (95% CI 2.3-4.2 months) and median overall survival was 20.1 months (95% CI 14.1-27.1 months). Treatment-related adverse events (AEs) occurred in 227 patients (64.7%). Grade 3-4 treatment-related AEs occurred in 39 patients (11.1%); 3 (0.9%) had grade 5 treatment-related AEs (myocarditis, pneumonia, and Guillain-Barre syndrome, n = 1 each). CONCLUSIONS: Pembrolizumab demonstrated clinically meaningful and durable benefit, with a high ORR of 30.8%, long median duration of response of 47.5 months, and manageable safety across a range of heavily pretreated, advanced MSI-H/dMMR noncolorectal cancers, providing support for use of pembrolizumab in this setting.

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study.

OBJECTIVE: Pembrolizumab demonstrated a clinically meaningful objective response rate in patients with previously treated, advanced MSI-H/dMMR endometrial cancer in the multicohort phase 2 KEYNOTE-158 study (ClinicalTrials.gov, NCT02628067). We present health-related quality of life (HRQoL) results for these patients. METHODS: This analysis included patients from cohorts D (endometrial cancer with any MSI status) and K (any MSI-H/dMMR solid tumor except colorectal) who had previously treated, advanced MSI-H/dMMR endometrial cancer. Patients received pembrolizumab 200 mg Q3W for 35 cycles. EORTC QLQ-C30 and EQ-5D-3L questionnaires were administered at baseline, at regular intervals during treatment, and 30 days after treatment discontinuation. Pre-specified exploratory analyses included changes from baseline to week 9 in QLQ-C30 global health status (GHS)/QoL and EQ-5D-3L visual analog scale (VAS) score for all patients and by best overall response. RESULTS: 84 of 90 enrolled patients completed ≥1 HRQoL questionnaire and were included in the analysis. QLQ-C30 and EQ-5D-3L compliance rates were 90% and 94%, respectively, at baseline, and 92% and 93% at week 9. Mean (95% CI) QLQ-C30 GHS/QoL scores improved from baseline to week 9 by 6.08 (0.71-11.46) points in the overall population, with greater improvement in patients who achieved complete or partial response (11.67 [5.33-18.00]-point increase). Mean (95% CI) EQ-5D-3L VAS scores improved by 6.00 (2.25-9.75) points in the overall population and 9.11 (5.24-12.98) points in patients with CR/PR. CONCLUSIONS: Pembrolizumab maintained or improved HRQoL in patients with previously treated, advanced MSI-H/dMMR endometrial cancer, further supporting efficacy and safety results from KEYNOTE-158 and pembrolizumab use in this setting.

Antiviral treatment with fluoxetine for rituximab-associated chronic echovirus 13 meningoencephalitis and myofasciitis.

BACKGROUND AND PURPOSE: Enterovirus infections pose a serious threat for patients with humoral deficiencies and may be lethal, whilst the efficacy of proposed treatment options such as corticosteroids, intravenous immunoglobulins and fluoxetine remains debated. METHODS: Viral clearance was investigated in a patient with rituximab-induced B-cell depletion and chronic echovirus 13 (E13) meningoencephalitis/myofasciitis in response to intravenous immunoglobulins and fluoxetine using sequential semi-quantitative E13 viral load measurements by real-time reverse transcription polymerase chain reaction. Fluoxetine concentrations in plasma and cerebrospinal fluid were determined by liquid chromatography mass spectrometry. RESULTS: Intravenous immunoglobulins appeared ineffective in this case of E13 infection, whereas virus clearance in cerebrospinal fluid was obtained after 167 days of oral fluoxetine. Since treatment with corticosteroids resulted in a flare of symptoms, rechallenge with viral load measurements was not attempted. CONCLUSION: In this report of a patient with rituximab-associated chronic echovirus 13 meningoencephalitis, viral clearance in response to single treatment options is assessed for the first time. Our observations further support the in vivo efficacy of fluoxetine against enteroviral infections. More research is needed to establish its efficacy in different enterovirus strains.

COVID-19 Vaccine Uptake and Its Impacts in a Cohort of Gay and Bisexual Men in Australia.

Successful use of biomedical forms of HIV risk-reduction may have predisposed many gay and bisexual men (GBM) to vaccination against COVID-19, which may, in turn, affect their sexual behavior. A total of 622 Australian GBM provided weekly data on COVID-19 vaccination history and sexual behaviour between 17 January 2021 and 22 June 2021. We identify factors associated with COVID-19 vaccination, and compare sexual behavior before and since vaccination. Mean age was 47.3 years (SD 14.0). At least one-dose vaccination coverage had reached 57.2%, and 61.3% reported that the majority of their friends intended to be vaccinated. Vaccinated men reported a mean of 1.11 (SD 2.10) weekly non-relationship sex partners before vaccination and 1.62 (SD 3.42) partners following vaccination. GBM demonstrated high confidence in COVID-19 vaccines. Their sexual activity increased following vaccination suggesting that greater sexual freedom may be a specific motivation for vaccine uptake among some men.

First live birth in China after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency.

OBJECTIVE: This article reports the first live birth after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency in China. METHODS: A patient with myelodysplastic syndrome received ovarian tissue cryopreservation before hematopoietic stem cell transplantation, and six ovarian cortex strips were thawed and transplanted into her peritoneal pocket 2 years later. RESULTS: Pregnancy occurred spontaneously 27 months after grafting, and a healthy girl was born at 38 weeks gestation. Until now, the child has developed normally without any major diseases. CONCLUSIONS: We report the first live birth resulting from ovarian tissue cryopreservation and transplantation in China.

[Safety of an inactivated 2019-nCoV vaccine (Vero) in adults aged 60 years and older].

Objective: To analyze the safety of an inactivated 2019-nCoV vaccine (Vero cell) in adults aged 60 years and older. Methods: A randomized, double-blind, placebo-controlled clinical study was conducted in May 2020 The eligible residents aged 60 and above were recruited in Renqiu city, Hebei Province. A total of 422 subjects (phase Ⅰ/Ⅱ:72/350) were enrolled. Two doses of the trial vaccine or placebo were randomly administered according to a 0 and 28-day immunization schedule. Subjects were randomly divided into two groups in Phase Ⅰ. Within each group, participants received vaccine or placebo in a ratio of 2∶1. Subjects were randomly divided into four groups in phase Ⅱ to receive low-dose, medium-dose, high-dose vaccine and placebo, respectively, in a ratio of 2∶2∶2∶1. A combination of regular follow-up and active reporting was used to observe adverse reactions within 28 days after vaccination, and compare the incidence rate of adverse reactions in the trial and control groups. Results: 422 subjects were (66.45±4.70) years old, and 48.82% were male (206/422). There were 100, 124, 124 and 74 patients enrolled into the low-dose, medium-dose, high-dose vaccine groups and the placebo group, respectively. One person without the vaccination was removed, and 421 participants who received at least one dose of vaccine were included in the safety analysis. Within 28 days after the first or second dose, a total of 20.67% (87/421) subjects had adverse reactions (both solicitation and non-solicitation). About 76 patients suffered grade 1 adverse reactions [18.05% (76/421)] and 22 patients suffered grade 2 adverse reactions [5.23% (22/421)]. No grade 3 or above adverse reactions occurred. A total of 19.71% (83/421) subjects had solicited adverse reactions. The most common grade 1 adverse reaction was injection site pain, followed by fever and fatigue. The most common grade 2 adverse reactions were fever and fatigue, followed by muscle pain and injection site redness. A total of 2.61% (11/421) subjects had unsolicited adverse reactions. A total of 1.66% (7/421) subjects had serious adverse events after vaccination, and no serious vaccine-related adverse events were reported. Conclusions: The inactivated SARS-CoV-2 vaccine is safe for people aged 60 years and above.

[Lung transplantation for pulmonary alveolar proteinosis: a case report and literature review].

Objective: To observe the efficacy of lung transplantation for pulmonary alveolar proteinosis (PAP) patients and to improve the understanding of the therapy. Methods: The clinical data of a patient with autoimmune PAP treated with sequential homogenous bilateral lung transplantation were described and the literatures were reviewed. Results: This 55-year-old female patient was diagnosed with autoimmune PAP and had been treated with whole lung lavage for 19 times, but only achieved short-term symptomatic relief after each operation. Inhalation of granulocyte macrophage colony stimulating factor occurred allergic reactions. Lung transplantation was performed on February 15, 2022, and a significant improvement in oxygenation and clinical symptoms were observed. The patient remained stable during follow-up. Conclusion: Treatment with lung transplantation is safe and effective for end-stage patients with PAP in the early phase, but the long-term effect remains to be observed.

[Changes of GSH-PX activity and γ-GCS mRNA expression in serum of workers exposed to manganese].

Objective: To explore the changes of γ-GCS mRNA expression and GSH-PX in serum of workers exposed to manganese in order to provide scientific basis for early diagnosis of manganese poisoning. Methods: In June 2017, a total of 180 workers from a motorcycle manufacturer were selected by stratified random sampling, including 115 welders as the exposure group and 65 administrative office workers as the Control Group, the exposure group was divided into high exposure group (43 persons) and low exposure group (72 persons) according to whether the exposure group exceeded the standard limit. The levels of γ-gcs Mrna expression and GSH-Px activity in serum were determined by Occupational Health Survey, and the differences of γ-gcs Mrna expression and GSH-Px activity among different groups were analyzed. Results: Compared with the control group, the serum GSH-Px activity was lower and the serum γ-GCS mRNA expression level was higher in the exposed group (F=370.52, 275.95, P<0.01) . Compared with the control group, there was significant difference in γ-GCS mRNA expression level and GSH-Px activity (F=0.475、1.06, P<0.01; F=48.53、111.70, P<0.01) . The concentrations of manganese in air, welding dust and urine were positively correlated with the level of γ-GCS mRNA (r=0.71, 0.50, 0.31, P<0.01) The serum GSH-Px activity was negatively correlated with the concentrations of manganese in air, welding dust and urine (r=-0.80, -0.52, -0.30, P< 0.01) , There was no correlation between Serum γ-GSH-Px activity and age and years of exposure (P>0.05) . Conclusion: Serum γ-GCS mRNA expression level and GSH-Px activity level can be used as early biomarkers of manganese poisoning. The concentrations of manganese in workplace air, welding dust and urine manganese in workers are the influencing factors.

Maternal and neonatal outcomes in 80 patients diagnosed with non-Hodgkin lymphoma during pregnancy: results from the International Network of Cancer, Infertility and Pregnancy.

This cohort study of the International Network on Cancer, Infertility and Pregnancy (INCIP) reports the maternal and neonatal outcomes of 80 pregnant patients diagnosed with non-Hodgkin lymphoma (NHL) between 1986 and 2019, focussing on 57 (71%) patients with diffuse large B-cell lymphoma (DLBCL). Of all 80 patients, 54 (68%) pregnant patients received chemotherapy; mostly (89%) CHOP-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens. Four early pregnancies were terminated. Among 76 ongoing pregnancies, there was one stillbirth (1·3%). Overall, there was a high incidence of small for gestational age neonates (39%), preterm delivery (52%), obstetric (41%) and neonatal complications (12·5%), and this could not exclusively be explained by the receipt of antenatal chemotherapy. Half of preterm deliveries (46%) were planned in order to tailor oncological treatment. The 3-year progression-free and overall survival for patients with DLBCL treated with rituximab-CHOP was 83·4% and 95·7% for limited stage (n = 29) and 60·6% and 73·3% for advanced stage (n = 15). Of 36 pregnant patients who received rituximab, five (13%) cases with neonatal complications and three (8%) with maternal infections were reported. In conclusion, standard treatment for DLBCL can be offered to pregnant patients in obstetric centres that cater for high-risk patients.

Neoadjuvant Treatment with Angiogenesis-Inhibitor Dovitinib Prior to Local Therapy in Hepatocellular Carcinoma: A Phase II Study.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence rates following locoregional treatment are high. As multireceptor tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFRs) are effective in advanced HCC, we assessed the efficacy and safety of neoadjuvant systemic treatment with dovitinib in early- and intermediate-stage HCC. MATERIALS AND METHODS: Twenty-four patients with modified Child-Pugh class A early- and intermediate-stage HCC received neoadjuvant oral dovitinib 500 mg daily (5 days on/2 days off) for 4 weeks, followed by locoregional therapy. Primary endpoints were objective response rates and intratumoral blood flow changes. Secondary endpoints were safety, pharmacodynamical plasma markers of VEGFR-blockade, time to progression (TTP), and overall survival (OS). RESULTS: Modified RECIST overall response rate was 48%, including 13% complete remission, and despite dose reduction/interruption in 83% of patients, intratumoral perfusion index decreased significantly. Grade 3-4 adverse events, most frequently (on-target) hypertension (54%), fatigue (25%), and thrombocytopenia (21%), occurred in 88% of patients. Plasma VEGF-A, VEGF-D, and placental growth factor increased significantly, whereas sTie-2 decreased, consistent with VEGFR-blockade. Following neoadjuvant dovitinib, all patients could proceed to their original planned locoregional treatment. No delayed toxicity occurred. Seven patients (three early, four intermediate stage) underwent orthotopic liver transplant after median 11.4 months. Censoring at transplantation, median TTP and OS were 16.8 and 34.8 months respectively; median cancer-specific survival was not reached. CONCLUSION: Already after a short 4-week dovitinib treatment period, intratumoral blood flow reduction and modest antitumor responses were observed. Although these results support use of systemic neoadjuvant strategies, the poor tolerability indicates that dovitinib dose adaptations are required in HCC. IMPLICATIONS FOR PRACTICE: Orthotopic liver transplantation may cure early and intermediate-stage hepatocellular carcinoma. Considering the expected waiting time >6 months because of donor liver scarcity, there is an unmet need for effective neoadjuvant downsizing strategies. Angiogenesis inhibition by dovitinib does not negatively affect subsequent invasive procedures, is safe to administer immediately before locoregional therapy, and may provide a novel treatment approach to improve patient outcomes if tolerability in patients with hepatocellular carcinoma can be improved by therapeutic drug monitoring and personalized dosing.

Multi-messenger nanoprobes of hidden magnetism in a strained manganite.

The ground-state properties of correlated electron systems can be extraordinarily sensitive to external stimuli, offering abundant platforms for functional materials. Using the multi-messenger combination of atomic force microscopy, cryogenic scanning near-field optical microscopy, magnetic force microscopy and ultrafast laser excitation, we demonstrate both 'writing' and 'erasing' of a metastable ferromagnetic metal phase in strained films of La2/3Ca1/3MnO3 (LCMO) with nanometre-resolved finesse. By tracking both optical conductivity and magnetism at the nanoscale, we reveal how strain-coupling underlies the dynamic growth, spontaneous nanotexture and first-order melting transition of this hidden photoinduced metal. Our first-principles calculations reveal that epitaxially engineered Jahn-Teller distortion can stabilize nearly degenerate antiferromagnetic insulator and ferromagnetic metal phases. We propose a Ginzburg-Landau description to rationalize the co-active interplay of strain, lattice distortions and magnetism nano-resolved here in strained LCMO, thus guiding future functional engineering of epitaxial oxides into the regime of phase-programmable materials.

Radio-sensitizing effects of microRNA-27a elevation in lung cancer cells by inhibiting ZEB1 expression and activating DNA damage repair pathway.

MicroRNAs (miRNAs or miRs) exert either as tumor-inhibiting or oncogenic roles in tumorigenesis of lung cancer. In the present study, we identified a novel microRNA (miR)-27a as being involved in the radiosensitivity of lung cancer cells. Therefore, we sought to characterize its potential underlying mechanism in lung cancer cell sensitivity to radiotherapy. To this end, A549 and H460 cells irradiated with 8 Gy irradiation (IR) were used as a cell model. RT-qPCR exhibited that the expression of miR-27a increased, whereas ZEB1 was poorly expressed in A549 and H460 cells exposed to IR. As reflected by dual-luciferase reporter gene assay, miR-27a could target and inversely modulate ZEB1 expression. Gain- and loss-of-function experiments exhibited that miR-27 inhibition promoted proliferation of IR-treated A549 and H460 cells and reduced the sensitivity of A549 and H460 cells to radiotherapy, which was rescued by silencing of ZEB1. Further, miR-27a inhibition disrupted the homologous recombination (HR)-mediated DNA repair, evidenced by reduced ATM, pCHK2 and Rad51 levels. Collectively, miR-27a activates HR-mediated DNA repair by inhibiting ZEB1 expression to enhance the radiosensitivity of lung cancer cells, highlighting a therapeutic target for lung cancer radiosensitivity.

First pregnancy in China after ovarian tissue transplantation to prevent premature ovarian insufficiency.

OBJECTIVE: This article reports the first case of pregnancy after frozen-thawed ovarian tissue transplantation to prevent iatrogenic premature ovarian insufficiency in China. METHODS: Ovarian tissue cryopreservation was performed in a patient with myelodysplastic syndrome (MDS) before multi-agent chemotherapy and hematopoietic stem cell transplantation. Two years later, she showed complete remission from MDS, and six frozen-thawed ovarian tissue strips were transplanted into the peritoneal pocket. RESULTS: The patient's ovarian activity was restored 3 months after transplantation, and pregnancy occurred spontaneously 27 months after grafting. Until now, the pregnancy has progressed for 30 weeks, and the repeated ultrasound showed normal fetal development. CONCLUSION: This is the first pregnancy resulting from ovarian tissue cryopreservation and transplantation in China.