Deintensified Chemoradiotherapy for Pretreatment Epstein-Barr Virus DNA-Selected Low-Risk Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Randomized Noninferiority Trial

PURPOSE Cumulative doses of 200 mg/m2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL. PATIENTS AND METHODS Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc. RESULTS Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, –4.3 to 9.1, Pnoninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life. CONCLUSION Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

Association of Menstrual Problems and Psycological Stress in Young Medical Students

Aim: To see if there was a link between menstruation issues and psychological stress among young medical students. Methods: A non-probability convenient sampling method was used to conduct an observational (cross-sectional) study on a sample of 180 university-bound students. Students were assessed for menstrual regularity associating with psychological stress by using Perceived Stress Scale in different universities of Lahore. Results: The study included approximately 92% of females with a regular menstrual cycle and 8% of females with an irregular menstrual cycle.While among irregular menstrual cycles, 5 had high levels of stress, 7 had moderate levels of stress, and 3 had mild levels of stress. The normal menstrual cycle group had 40 females with high levels of stress, 121 females with moderate levels of stress, and four females with low levels of stress. Conclusion: Although fewer students suffered from menstruation difficulties, the majority of them, including those who did not, experienced psychological stress. Keywords: Menstrual disorders, dysmenorrheal, abnormal menstrual cycle, stress

Gonadotropin-releasing Hormone Agonist Down Regulation Combined With Hormone Replacement Therapy Improves the Reproductive Outcome in the Frozen-thawed Embryo Transfer Cycle of Elderly Patients With Idiopathic Recurrent Implantation Failure

BackgroundTo determine whether Gonadotropin-releasing hormone (GnRH) agonist down regulation combined with hormone replacement treatment (HRT) can improve the reproductive outcomes in the frozen thawed embryo transfer (FET) cycle of elderly patients with idiopathic recurrent implantation failure (RIF). MethodsThis is a retrospective cohort study analyzing 594 elderly patients (aged 36~43 years old) undergoing third cleavage embryo or blastocyst transfer over nearly 5-year period (January 2015–November 2020) at Northwest Women’s and Children’s Hospital after IVF-ICSI cycles. Patients with known endometriosis or adenomyosis were excluded from the study.According to different endometrial preparation protocols, patients were divided into three groups: natural cycle group (NC, n=62), hormone replacement treatment cycle group (HRT, n=194) and GnRH agonist down regulation combined with HRT cycle group (GnRHa-HRT, n=290).Live birth rate was primary outcome while clinical pregnancy rate, miscarriage rate, on going pregnancy rate were secondary outcomes. ResultsLive birth rate in the GnRHa-HRT group (31.90%) was significantly higher than that in the HRT (21.65%) or NC (16.13%) groups (P<0.0001). Logistic regression model adjusting for the potential confounders showed that patients in the GnRHa-HRT group have significantly higher live birth rate compared with those in the HRT group (OR, 2.708; 95%CI,1.251-5.864, P=0.011). However, live birth rate was not significantly different between GnRHa-HRT and NC groups (OR, 1.509; 95% CI,0.657-3.463, P=0.332), which could be due to the small sample size in the NC group.ConclusionsGnRHa-HRT protocol improves live birth rate in FET cycles of elderly patients with RIF. We hypothesize that GnRHa-HRT protocol enhances implantation related factors and promotes optimal endometrium receptivity, leading to the improved live birth rate. These findings are also useful for further investigating the underlying mechanism of GnRHa-HRT protocol in improving the reproductive outcomes of elderly patients with RIF.Trial registration:The research protocol was approved by the hospital institutional ethics committee (2021002).

Analysis of the levels of hope and influencing factors in infertile women with first-time and repeated IVF-ET cycles

Purpose To explore the hope levels and influencing factors in infertile women undergoing first-time and repeated in vitro fertilization-embryo transfer (IVF-ET) cycles. Methods This study was a cross-sectional and convenient sampling study conducted among patients undergoing IVF-ET from January to June 2019. Patients were divided into first-time and repeated groups by the number of IVF-ET cycles, and then a questionnaire survey was administered. The questionnaire included demographic information, Herth hope index (HHI) scale, Locke-Wallace short marital-adjustment test scale and social support rating scale. Multiple linear regression was used to analyse the influencing factors associated with hope levels. Results A total of 298 IVF-ET patients were recruited for the study, including 150 (50.3%) in the first-time cycle group and 148 (49.7%) in the repeated cycle group. The HHI score of the repeated cycle group was significantly lower than that of the first-time cycle group (34.4 ± 3.5 vs. 37.5 ± 3.7, P < 0.001). Multiple linear regression analysis indicated that repeated IVF-ET and age were independently negatively correlated with HHI, with standardized coefficient β values of − 0.895 and − 0.223, respectively (both P < 0.001). High education level (P = 0.002), high monthly income (P = 0.020), high degree of short marital-adjustment test (P < 0.001) and social support rating (P < 0.001) were independently positively correlated with HHI. Conclusion Infertile women undergoing repeated IVF-ET have low hope levels. Maintaining a good marriage adjustment and establishing a good social support and relationship network could effectively improve their hope levels.

The Effect of the Menstrual Cycle and Oral Contraceptive Cycle on Muscle Performance and Perceptual Measures

Most reproductive-aged women are exposed to fluctuating female steroid hormones due to the menstrual cycle or oral contraceptive use. This study investigated the potential effect of the menstrual cycle and combined monophasic oral contraceptive cycle on various aspects of muscle performance. Thirty active females (12 with a natural menstrual cycle, 10 taking a high-androgenicity oral contraceptive and 8 taking a low-androgenicity oral contraceptive), aged 18 to 30 years, were tested three times throughout one menstrual or oral contraceptive cycle. Counter-movement jumps, bilateral hop jumps, handgrip strength, isometric knee extensor strength and isokinetic knee flexion and extension were assessed. Perceptual ratings of fatigue, muscle soreness, pain and mood were recorded. Most variables showed no significant changes over the menstrual or oral contraceptive cycle. However, for the menstrual cycle group, isokinetic knee flexion at 240° s−1, and time of flight in bilateral hopping and counter movement jumps showed better results during the mid-luteal phase compared with the late follicular phase. For the high-androgenicity oral contraceptive group, isokinetic knee flexion at 240° s−1 was significantly higher in the late hormone phase compared with the early hormone phase. For the low-androgenicity oral contraceptive group, time of flight for the counter-movement jumps was lower in the late hormone phase compared with the early hormone phase. The findings indicate that faster and explosive aspects of muscle performance may be influenced by endogenous and exogenous female hormones.

Effects of Treadmill Training and Stationary Cycling Training to Improve Ambulatory Function and Cardiovascular Fitness

Background: Stroke is a universal health care disease, the important cause of long time disability in world. Stroke leads to an inactive living, physical restrictions, and not good physical levels, which are related with common post-stroke participation limits. Aerobic capability and walking ability are decreased in old chronic patients of stroke. Aim: To determine the effects of treadmill training and stationary cycling training to improve ambulatory function and cardiovascular fitness in hemiparetic stroke patients Methods: 54 chronic stroke patients were allocated to treadmill training group(n=27) or stationary cycle exercise group (n=27). All participants received conventional physical therapy along with treadmill or stationary cycle training. The 10MWT was conducted to measure gait function and 6 min walk test was used to measure cardiovascular health. Results: The mean of treadmill group for 10 meter walk test is 10.01 + 15.48. The mean of stationary cycle group for 10 meter walk test is 9.80 + 6.77. The mean of treadmill group for 6 min walk test is 22.04+ 17.45. The mean of stationary cycle group for 6 min walk test is 23.20+ 22.92. The p value of 0.000 shows significant difference. This significant difference reflects that both interventions show equal improvement in participants. There is significant difference between pre and post treatment values of both interventions. Both intervention groups displayed significant effect in ambulatory functions and cardiovascular fitness. The results between groups were non significant, it means both interventions showed equal effect but results with in groups were significant. Conclusion: The study showed that treadmill training and stationary cycling training equally enhanced the gait ability and cardiovascular health of chronic stroke patients. Therefore, these exercises could be used to enhance walking and cardiovascular health in management of stroke. Keywords: treadmill training, stationary cycle training, ambulatory function, cardiovascular fitness, stroke

Effect of Different Sintering Cycles on the Surface Hardness of Full Contour Monolithic Zirconia – An In Vitro Comparative Study

BACKGROUND This in-vitro study was conducted to compare the effect of different sintering cycles on the surface hardness of full contour monolithic Zirconia. METHODS In this in-vitro study, a total of 28 bar shaped Zirconia samples of final dimensions 20 x 4 x 2 mm were fabricated using Amann Girrbach CAD - CAM unit. These samples were randomly allocated into four groups with 7 samples in each group namely, Group 1, 2, 3 and 4 (Group 1: Long sintering cycle, Group 2: Intermediate sintering cycle, Group 3: Short sintering cycle, Group 4: Ultra-short sintering cycle) and sintered under the respective sintering cycles. The Ceramill® Therm sintering furnace provided 3 sintering cycles ranging from the longest Group - 1 (19 hours), to the short sintering cycle Group - 3 (8 hours), with an intermediate sintering cycle Group - 2 (15hours). The Zircom sintering furnace provided an ultra-short sintering cycle Group - 4 (2 hours). The testing of surface hardness was performed using TECSOL hardness tester. Statistical analysis of the collected data was performed by one - way ANOVA using SPSS software. Multiple comparison was done using post-hoc Tukey’s test. RESULTS One - way ANOVA showed statistically significant difference in the surface hardness of different samples (P < 0.05). The highest mean hardness was observed in Group 3 with 2713.757 + 233.89 VHN, followed by Group 2 with 2595.714 + 62.35 VHN, followed by Group 4 with 2518.600 + 103.65 VHN and Group 1 with the least, 1734.300 + 460.20 VHN. CONCLUSIONS The surface hardness of full contour monolithic Zirconia was influenced to some extent by various sintering cycles. The longest sintering cycle showed the least surface hardness whereas, the short sintering cycle showed the highest surface hardness. Also the ultra-short sintering cycle of 2 hours exhibited surface hardness comparable to the other sintering cycles with longer duration, making it a viable alternative to the conventional sintering cycles. KEY WORDS Monolithic Zirconia, CAD - CAM, Sintering, Hardness

Optimal Duration of Neoadjuvant Taxane and Carboplatin Combined With Anti-HER2 Targeted Therapy for HER2-Positive Breast Cancer

BackgroundTaxane, carboplatin and trastuzumab (TCH) is an effective neoadjuvant regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer with high pathologic complete response (pCR) rate. The KATHERINE trial changes the outlook for high-risk HER2-positive breast cancer, which suggests that escalation treatment for patients with residual disease after neoadjuvant anti-HER2 therapy may improve survival. The major objective of this study was to investigate the fewest cycles of neoadjuvant TCH therapy needed to screen out non-pCR patients.MethodsThis retrospective study included patients with HER2-positive breast cancer who received either four or six cycles of TCH preoperatively at Fudan University Shanghai Cancer Center between 2008 and 2019. The pCR status was evaluated, and relevant factors associated with pCR were identified using univariate and multivariable analyses. The pathological results of core needle biopsy (CNB) in the breast tumor after two cycles of neoadjuvant chemotherapy were also collected. Kaplan-Meier curve was used to estimate the event-free survival (EFS).ResultsOf 758 eligible patients, 303 were included and analyzed in the four-cycle group and 455 in the six-cycle group. There was no significant difference between the two groups in terms of the pCR rate (46.5% [95% CI 40.9% - 52.2%] in the four-cycle group and 49.9% [95% CI 45.3% - 54.5%] in the six-cycle group, p = 0.365) or the four-year EFS (90.8% in four-cycle group and 93.8% in six-cycle group; p = 0.264). Multivariable analysis indicated that a negative hormone receptor status and the weekly paclitaxel were independent factors for predicting pCR. After adjusting for factors in the multivariable analysis, there was still no significant difference between four and six cycles of neoadjuvant TCH (OR = 1.252, 95% CI 0.904 - 1.733, p = 0.176). Furthermore, 17.9% patients with invasive carcinoma on CNB after two cycles of TCH ultimately achieved pCR in the breast after the completion of neoadjuvant treatment.ConclusionFour cycles of taxane/carboplatin-based neoadjuvant anti-HER2 therapy may be applied as an optimal treatment duration for screening high-risk HER2-positive breast cancer patients for escalation treatment. Further prospective study is warranted.

De-intensified chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma based on plasma EBV DNA: A phase 2 randomized noninferiority trial.

110 Background: The cisplatin-based chemoradiotherapy (CCRT), given at a dose of 100 mg/m2 for 3 cycles during radiotherapy, is the major treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). As several retrospective studies showed that receiving a cumulative cisplatin dose of 200 mg/m2 can bring survival benefits to NPC patients, we sought to test the non-inferiority of 2-cycle concurrent cisplatin over 3-cycle in locoregionally advanced NPC with Epstein-barr virus (EBV) DNA levels < 4000 copies/ml. Methods: We did a non-inferiority, phase 2, randomised controlled trial. Patients were enrolled with stage III–IVB NPC, EBV DNA levels < 4000 copies/ml, aged 18–70 and adequate haematological, renal, and hepatic function. Eligible patients were randomly assigned (1:1) to receive 2 or 3 cycles of cisplatin-based CCRT. Patients in the 2-cycle group were scheduled to receive 100 mg/m2 cisplatin given every 3 weeks concurrently with radiotherapy, and patients in the 3-cycle group received 100 mg/m2 cisplatin given every 3 weeks for 3 cycles. Randomization was done by a computer-generated random number code with a block size of six, stratified by clinical stage III or IV. The primary endpoint was 3-year progression-free survival (PFS), with a non-inferiority margin of 10%. This study was registered with ClinicalTrials.gov, ID. NCT02871518. Results: Between September 2016 and October 2018, 342 patients were enrolled, of whom 332 were randomly assigned to receive 2 or 3 cycles of cisplatin. 314 (94.6%) patients completed protocol-defined cycles of chemotherapy. After median follow-up of 33.6 months, 20 (12.0%) patients in the 2-cycle group and 17 (10.2%) patients in the 3-cycle group had tumor progression, and the 3-year PFS rates were 88.0% and 90.4% respectively, with a difference of 2.4% (95%CI -4.3 to 9.1, Pnon-inferiority < 0.001). In the per-protocol analysis, 3-year PFS was 88.5% in the 2-cycle group and 90.6% in the 3-cycle group, with a difference of 2.1% (95% CI –4.7 to 8.9; Pnon-inferiority= 0.001). No significant difference was observed concerning OS, LRRFS and DMFS. The grade 3 or 4 acute adverse events were recorded in 113 (68.1%) patients in the 2-cycle group and 116 (69.9%) patients in the 3-cycle group. Patients in the 3-cycle group was observed to have significantly more hyponatremia. Besides, patients in the 3-cycle group presented with more grade 1 or 2 dry mouth, dysphagia, weight loss, fatigue, constipation, fever, mucositis and dermatitis. More grade 3 or 4 anorexia, mucositis and dermatitis were also recorded in the 3-cycle group. No patients died from treatment-related toxicities. Conclusions: IMRT plus 2 cycles of concurrent 100 mg/m2 cisplatin could be an alternative option for patients with low-risk locoregionally advanced NPC. Further phase III studies are needed to validate the findings of this study. Clinical trial information: NCT02871518.

Frozen vs. fresh cycles IVF outcomes: retrospective study from an Indonesian IVF centre

Objective To compare the live birth rates (LBR) and neonatal outcomes of frozen cycle in vitro fertilization (IVF) with fresh cycle IVF in the Indonesian population. Results This was retrospective study using secondary data of IVF patients at a private fertility centre. Study recruitment was between 3/8/2018 and 31/12/2019. Total sampling included all patients undergoing oocyte retrieval and embryo transfer within recruitment period. Patients undergoing fresh IVF cycles and frozen IVF cycles were compared. 351 patients were recruited: 68.1% (239/351) underwent fresh cycles and 31.9% (112/351) frozen cycles. AMH was significantly higher in frozen cycle group (p = 0.04). Ovulatory disorder was significantly higher in frozen cycle group (p = 0.001). Among patients aged ≤ 30, fresh cycle group had significantly higher LBR (p = 0.02). Among those with ovulatory disorder, LBR was significantly higher with frozen cycle. No significant LBR difference was noted with other infertility causes. When stratified according to pregnancy order, frozen cycle patients had significantly higher birth lengths (p = 0.03) but not length of gestation nor neonatal birthweights. There was no significant difference in the proportion of biochemical pregnancy resulting in LBR (p = 0.08). To conclude, frozen cycle provided higher LBR among patients with ovulatory disorder but fresh cycle was beneficial among patients aged ≤ 30.