Effects of SGLT2 Inhibitors with and without Metformin in High-Risk, Treatment-Naïve Patients with Diabetes.

Background: Contemporary evidence supports the cardiovascular and renal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2is) in patients with diabetes. While metformin has traditionally been recommended as a first-line treatment, its exact role in improving cardiovascular outcomes remains uncertain. This study aims to evaluate the impact of combination therapy with metformin on the cardiovascular and renal outcomes in high-risk, treatment-naïve diabetic patients who have undergone SGLT2i therapy. Methods: Using the National Health Insurance Research Database in Taiwan, a retrospective cohort study was conducted. Treatment-naïve patients with diabetes and established atherosclerotic cardiovascular disease (ASCVD) undertaking SGLT2i therapy from 1 January 2016 to 31 December 2021 were included. Patients were categorized based on the concomitant use of metformin. Propensity score matching was employed to minimize confounding factors. The primary outcome was major adverse cardiovascular events (MACEs), with secondary outcomes including cardiovascular death, hospitalization for heart failure, and renal outcomes. Results: In total, 10,151 treatment-naïve diabetic patients with ASCVD were identified, with 2570 in the only SGLT2i therapy group and 7581 in the SGLT2i plus metformin group. In total, 2262 pairs were analyzed after propensity score adjustment. The risk of MACEs (36.6 vs. 42.1 events per 1000 person-years; hazard ratio 0.87, 95% confidence interval 0.70-1.09) and other outcomes did not significantly differ between the two treatment groups. Conclusions: In high-risk, treatment-naïve diabetic patients, initiating SGLT2i therapy alone or in combination with metformin resulted in comparable cardiovascular and renal outcomes. These findings suggest that metformin might not be mandatory as a first-line treatment for achieving cardiovascular benefits in such patients.

Progesterone in Pregnancy: Evidence-Based Strategies to Reduce Miscarriage and Enhance Assisted Reproductive Technology.

The incidence of miscarriage in early pregnancy, between 5-20 weeks, is common, with a prevalence of between 5-22% of all pregnancies. Miscarriage can have physical, social, and mental health impacts on women and their families. In societies such as Taiwan, where the birth rate is falling and life expectancy is increasing, there is concern that factors that reduce birth rates will have detrimental economic and societal effects. Progesterone has a significant role in maintaining early and successful pregnancy to term. Evidence from preclinical and clinical research on the roles of progesterone has supported recent clinical guidelines in obstetrics and gynecology to reduce rates of early miscarriage and improve methods of assisted reproductive technology (ART). This article aims to present an evidence-based review of current recommendations for the use of progesterone in early pregnancy to reduce miscarriage rates and in luteal phase support for ART, including embryo transfer.

Heart rate variability and behavioral alterations during prepartum period in dairy cows as predictors of calving: a preliminary study.

OBJECTIVE: Parturition is crucial for dams, their calves, and cow managers. The prediction of calving time, which assists cow managers to decide on the relocation of cows to maternity pens and necessity of human supervision, is a pivotal aspect of livestock farming. However, existing methods of predicting calving time in dairy cows based on hormonal changes and clinical symptoms are time-consuming and yield unreliable predictions. Accordingly, we investigated whether heart rate variability (HRV) which is a non-invasive assessment of autonomic nervous system (ANS) activity and behavior during the prepartum period would be useful for predicting calving time in dairy cows. METHODS: Eight pregnant cows were surveilled under electrocardiogram and video recordings for HRV and behavioral analyses, respectively. HRV parameters in time and frequency domains were evaluated. A 24-h time budget was calculated for each of six types of behavior (standing and lying with or without rumination, sleeping, and eating). RESULTS: Heart rate on calving day is considerably higher than those recorded on the days preceding calving. Low frequency power declined, whereas high frequency power escalated on the calving day compared to the period between 24 and 48 h before calving. The time budget for ruminating while lying decreased and that while standing increased markedly on the calving day compared to those allocated on the preceding days; nonetheless, the total time budget for ruminating did not differ during the prepartum period. CONCLUSION: We elucidated the ANS activity and behavioral profiles during prepartum period. Our results confirm that HRV parameters and behavior are useful for predicting calving time, and interestingly indicate that the time budget for ruminating while standing (or lying) may serve as a valuable predictor of calving. Collectively, our findings lay the foundation for future investigations to determine other potential predictors and formulate an algorithm for predicting calving time.

Post-exercise left atrial conduit strain predicted hemodynamic change in heart failure with preserved ejection fraction.

OBJECTIVES: Left ventricle function directly impacts left atrial (LA) conduit function, and LA conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Pulmonary capillary wedge pressure (PCWP) before and during exercise is the current gold standard for diagnosing HFpEF. Post-exercise ΔPCWP can lead to worse long-term outcomes. This study examined the correlation between LA strain and post-exercise ΔPCWP in patients with HFpEF. METHODS: We enrolled 100 subjects, including 74 with HFpEF and 26 with non-cardiac dyspnea, from November 2017 to December 2020. Subjects underwent echocardiography, invasive cardiac catheterization, and expired gas analysis at rest and during exercise. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and PCWP were recorded during cardiac catheterization. Cardiac output, stroke volume, pulmonary vascular resistance, pulmonary artery compliance, systemic vascular resistance, and LV stroke work were calculated using standard formulas. RESULTS: Exercise LA conduit strain significantly correlated with both post-exercise ΔPCWP (r = - 0.707, p < 0.001) and exercise PCWP (r = - 0.659; p < 0.001). Exercise LA conduit strain differentiated patients who did and did not meet the 2016 European Society of Cardiology HFpEF criteria with an area under the curve of 0.69 (95% confidence interval, 0.548-0.831) using a cutoff value of 14.25, with a sensitivity of 0.64 and a specificity of 0.68. CONCLUSIONS: Exercise LA conduit strain significantly correlates with post-exercise ΔPCWP and has a comparable power to identify patients with HFpEF. Additional studies are warranted to confirm the ability of LA conduit strain to predict long-term outcomes among patients with HFpEF. CLINICAL RELEVANCE STATEMENT: Exercise left atrial conduit strain was highly associated with the difference of post-exercise pulmonary capillary wedge pressure and may indicate increased mortality risk in patients with heart failure with preserved ejection fraction, and also has comparable diagnostic ability. KEY POINTS: • Left atrial conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction. • Left atrial conduit strain during exercise can identify patients with heart failure with preserved ejection fraction. • Exercise left atrial conduit strain significantly correlates with the difference of pulmonary capillary wedge pressure during and before exercise which might predict the long-term outcomes of heart failure with preserved ejection fraction patients.

Right Ventricular-Vascular Uncoupling Predicts Pulmonary Hypertension in Clinically Diagnosed Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Pulmonary hypertension (PH) is highly prevalent in patients with heart failure with preserved ejection fraction (HFpEF), and it is a strong predictor of adverse outcomes. We aimed to determine possible echocardiographic parameters to predict the presence of PH in patients with HFpEF. METHODS AND RESULTS: A total of 113 patients with HFpEF were prospectively enrolled from November 2017 to July 2022. The patients underwent invasive cardiac catheterization and simultaneous echocardiography at rest and during exercise. The parameters indicating right ventricle-pulmonary artery uncoupling, including tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) and tricuspid annular systolic velocity (TAS')/PASP were calculated. Receiver operating characteristic curve analysis was used to determine the optimal cut-off points of TAPSE/PASP and TAS'/PASP to differentiate patients with HFpEF with PH from those without PH. Sixty-eight patients with HFpEF with PH and 45 without PH were included. Those with PH had lower TAPSE/PASP and TAS'/PASP at rest and during exercise compared with those without PH. Both resting/stress TAPSE/PASP and TAS'/PASP were correlated with rest/exercise pulmonary capillary wedge pressure and mean pulmonary artery pressure. In multivariable regression analysis, TAPSE/PASP remained a significant predictor of exercise pulmonary capillary wedge pressure and mean pulmonary artery pressure. In receiver operating characteristic curve analysis, the optimal cut-off points of TAPSE/PASP and TAS'/PASP to differentiate patients with HFpEF with PH from those without PH were ≤0.62 and ≤0.47, respectively. CONCLUSIONS: Right ventricle-pulmonary artery uncoupling is closely correlated with abnormal rest/exercise hemodynamics (pulmonary capillary wedge pressure and mean pulmonary artery pressure) in patients with HFpEF. TAPSE/PASP and TAS'/PASP can be useful parameters to detect PH in patients with HFpEF.

Prediction of microdissection testicular sperm extraction outcomes of azoospermic patients post-chemotherapy using cyclophosphamide equivalent dose.

PURPOSE: We determined the sperm retrieval rate in men with persistent azoospermia post-chemotherapy in relation to cyclophosphamide equivalent dose (CED), a unit for quantifying alkylating agent exposure. METHODS: Medical records were retrospectively reviewed of 1098 patients diagnosed with non-obstructive azoospermia who had undergone microdissection testicular sperm extraction (mTESE) between January 2010 and 2021 at our institution. Twenty-three patients with a prior history of chemotherapy were included in the study. Oncological data, chemotherapy regime, and dosage were reviewed. The pretreatment hormone profile, CED, and mTESE outcomes were analyzed. RESULTS: Testicular spermatozoa were successfully retrieved from 11 patients (47%). The mean patient age was 37.3 years (range, 27-41 years), and mean time interval from chemotherapy to mTESE, 11.8 years (range, 1-45 years). Patients exposed to alkylating agents had significantly lower sperm retrieval rates than those not exposed to alkylating agents (1/9, 11% vs. 10/14, 71%, p = 0.009). No men with CED > 4000 mg/m2 (n = 6) had viable sperm in the testes during mTESE. Moreover, patients diagnosed with testicular non-seminomatous germ cell tumors had a favorable sperm retrieval rate (67%) compared to patients with lymphoma (20%) or leukemia (33%). CONCLUSION: Patients with permanent azoospermia post-chemotherapy have a lower testicular sperm retrieval rate when the chemotherapy regimen included alkylating agents. In cases where patients have undergone more intensive gonadotoxic treatments, such as higher CED, the likelihood of successful sperm retrieval is low. It is advisable to counsel such patients using the CED model prior to considering surgical sperm retrieval.

Magnetic field induced dose effects in radiation therapy using MR-linacs.

MR-guided radiotherapy (MRgRT) is one of the most significant advances in radiotherapy in recent years. The hybrid systems were designed to visualize patient anatomical and physiological changes during the course of radiotherapy, enabling more precise treatment. However, before MR-linacs reach their full potential in delivering safe and accurate treatments to patients, the radiotherapy team must understand how a magnetic field alters the dosimetric properties of the radiation beam and its potential impact on treatment quality and clinical outcomes. This review aims to provide an in-depth description of the magnetic field induced dose effects for the two widely available systems, the 0.35 T and the 1.5 T MR-linacs. In MR-linac treatments, the primary photon beam passes through MR components that never exist in conventional linacs, which alter both in-field and out-of-field doses. More importantly, the interplay between the always-on magnetic field and the secondary electrons is not negligible. This interplay affects dose deposition in the patient, resulting in reduced in-field skin dose due to purged-out contaminant electrons, shortened build-up distance and a shifted crossline profile owing to asymmetric dose kernel. Especially two effects, namely, electron return effect (ERE) and electron stream effect (ESE), are not seen in conventional radiotherapy. This review also summarizes the clinical observations on the site-specific treatments influenced mostly by the magnetic field. In MR-linac treatment, the head and neck region is one of the most challenging sites as ERE occurs at low and high density tissue interfaces and around air cavities, generating hot and cold spots. In breast cancer treatment, consideration should be given to the increased in-field skin dose induced by ERE and the increased out-of-field dose caused by ESE for regions such as the ears, chin, and neck. In lung cancer treatments, tissue inhomogeneity combined with ERE will exacerbate target dose heterogeneity and increase or decrease interface dose. Lastly, treatment in the abdomen and pelvic region will be affected by the presence of gas pockets near the target. The review provides practical recommendations to mitigate these effects.

Feasibility of repeat microdissection testicular sperm extraction within 6 months for nonobstructive azoospermia.

BACKGROUND: Microdissection testicular sperm extraction (mTESE) is the mainstay of sperm retrieval in men with nonobstructive azoospermia (NOA). Some experts believe that a resting period of ≥6 months is required between procedures to ensure better sperm retrieval rates and fewer complications. However, no scientific studies have investigated how long patients should wait before arranging a second mTESE procedure. This retrospective study aimed to evaluate whether good success rates are still achieved when a repeat mTESE procedure is performed within 6 months. METHODS: Total 146 patients with NOA who underwent mTESE twice from the same testis between May 2012 and September 2019 were retrospectively collected. These patients were categorized into three groups according to the time interval between the two mTESE surgeries, with 44, 60, and 42 patients undergoing a repeat mTESE after <3 months (group I), between 3 and 6 months (group II), and >6 months (group III) after the first procedure, respectively. RESULTS: No significant differences were observed between groups in terms of patient characteristics and preoperative hormone profiles. Overall sperm retrieval rates did not differ among the three groups (93.2%, 90.0%, and 88.1% in groups I, II, and III, respectively [ p = 0.719]), nor did fertility outcomes, including rates of fertilization, biochemical pregnancy, clinical pregnancy, and cumulative live births. CONCLUSION: Sperm retrieval rates for repeat mTESE procedures were consistently high, even when the second procedure was performed within 6 months of the first. Repeat mTESE within 6 months is not a limitation for patients with NOA, if required clinically.

Clinical implementation of kVCT-guided tomotherapy with ClearRT.

A helical fan-beam kilovoltage computed tomography (kVCT) was recently introduced into Tomotherapy units. This study aims to share the initial experience of kVCT in clinical workflow, compare its performance with that of the existing megavoltage computed tomography (MVCT), and explore its potential in adaptive planning. We retrospectively enrolled 23 patients who underwent both MVCT and kVCT scans. The clinical performance data regarding image acquisition time, nominal dose length product (DLP), registration time and registration corrections were extracted and compared. Image quality was scored by six experienced radiation therapists and quantified based on phantom measurements. CT number stability and the implementation of adaptive radiotherapy were dosimetrically evaluated by performing the dose recalculation on kVCT. Compared to MVCT, kVCT significantly reduced DLP (except the highest kVp protocol), image acquisition and registration time. KVCT obtained higher scores than MVCT on all criteria except artifacts. Phantom measurements also revealed a better image performance characterization of kVCT except for image uniformity. The CT number variation could lead to a dose difference of 0.5% for D95% of target and Dmean of organ-at-risk. For the treatment planning with kVCT, a systematic dose difference (> 1%) in PTV dose metrics was observed at regions with large longitudinal density discontinuities compared to the reference plans. The new kVCT imaging provides enhanced soft-tissue visualization. The improved efficiency with kVCT-guided treatment will allow more patients to be treated each day. In most cases, the dose calculation accuracy of kVCT images is acceptable except for regions with severe artifacts.

Magnetic Resonance-Guided Radiation Therapy of Patients With Cardiovascular Implantable Electronic Device on a 1.5 T Magnetic Resonance-Linac.

Magnetic resonance-guided radiation therapy is reported for treating patients with an insertable cardiac monitor and implantable cardiac pacemakers. All treatments were delivered using a 1.5 T MR-Linac. Among the 4 patients, 2 were treated with stereotactic body radiation therapy at a dose of 40 Gy in 5 fractions. A clinical safety protocol was developed to address the decision-making and patient selection, as well as the clarified responsibilities of different parties for management of patients with cardiovascular implantable electronic devices. Dose estimation based on out-of-field dose data are necessary for cardiovascular implantable electronic devices located outside the treatment fields.

Out-of-field dose and its constituent components for a 1.5 T MR-Linac.

This study aims to quantify the relative contributions of phantom scatter, collimator scatter and head leakage to the out-of-field doses (OFDs) of both static fields and clinical intensity-modulated radiation therapy (IMRT) treatments in a 1.5 T MR-Linac. The OFDs of static fields were measured at increasing distances from the field edge in an MR-conditional water phantom. Inline scans at depths of dmax (14 mm), 50 and 100 mm were performed for static fields of 5 × 5, 10 × 10 and 15 × 15 cm2under three different conditions: full scatter, with phantom scatter prevented, and head leakage only. Crossline scans at isocenter and offset positions were performed in full scatter condition. EBT3 radiochromic films were placed at 100 mm depth of solid water phantom to measure the OFD of clinical IMRT plans. All water tank data were normalized to Dmax of a 10 × 10 cm2field and the film results were presented as a fraction of the target mean dose.The OFD in the inline direction varied from 3.5% (15 × 15 cm2, 100 mm depth, 50 mm distance) to 0.014% (5 × 5 cm2, dmax, 400 mm distance). For all static fields, the collimator scatter was higher than the phantom scatter and head leakage at a distance of 100-400 mm. Head leakage remained the smallest among the three components, except at long distances (>375 mm) with small field size. Compared to the inline scans, the crossline scans at the isocenter showed higher doses at distances longer than 80 mm. All crossline profiles at longitudinal offset positions showed a cone shape with laterally shifted maxima. The OFD of IMRT deliveries varied with different target size. For prostate stereotactic body radiation therapy (SBRT) treatment, the OFD decreased from 2% to 0.03% at a distance of 50-500 mm. The OFDs have been measured for a 1.5 T MR-Linac. The presented dosimetric data are valuable for radiation safety assessments on patients treated with the MR-Linac, such as evaluating carcinogenic risk and radiation exposure to cardiac implantable electronic devices.

Structural and biochemical insights into a hyperthermostable urate oxidase from Thermobispora bispora for hyperuricemia and gout therapy.

Microbial urate oxidase has emerged as a potential source of therapeutic properties for hyperuricemia in arthritic gout and renal disease. The thermostability and long-term thermal tolerance of the enzyme need to be established to prolong its therapeutic effects. Here, we present the biochemical and structural aspects of a hyperthermostable urate oxidase (TbUox) from the thermophilic microorganism Thermobispora bispora. Enzymatic characterization of TbUox revealed that it was active over a wide range of temperatures, from 30 to 70 °C, with optimal activity at 65 °C and pH 8.0, which suggests its applicability under physiological conditions. Moreover, TbUox exhibits high thermostability from 10 to 65 °C, with Tm of 70.3 °C and near-neutral pH stability from pH 7.0 to 8.0 and high thermal tolerance. The crystal structures of TbUox revealed a distinct feature of the C-terminal loop extensions that may help with protein stability via inter-subunit interactions. In addition, the high thermal tolerance of TbUox may be contributed by the extensive inter-subunit contacts via salt bridges, hydrogen bonds, and hydrophobic interactions. The findings in this study provide a molecular basis for the thermophilic TbUox urate oxidase for application in hyperuricemia and gout therapy.

Molecular Elucidation of a Urate Oxidase from Deinococcus radiodurans for Hyperuricemia and Gout Therapy.

Urate oxidase initiates the uric acid degradation pathways and is extensively used for protein drug development for gout therapy and serum uric acid diagnosis. We first present the biochemical and structural elucidation of a urate oxidase from the extremophile microorganism Deinococcus radiodurans (DrUox). From enzyme characterization, DrUox showed optimal catalytic ability at 30 °C and pH 9.0 with high stability under physiological conditions. Only the Mg2+ ion moderately elevated its activity, which indicates the characteristic of the cofactor-free urate oxidase family. Of note, DrUox is thermostable in mesophilic conditions. It retains almost 100% activity when incubated at 25 °C and 37 °C for 24 h. In this study, we characterized a thermostable urate oxidase, DrUox with high catalytic efficiency and thermal stability, which strengthens its potential for medical applications.

Reproductive outcomes of microdissection testicular sperm extraction in hypogonadotropic hypogonadal azoospermic men after gonadotropin therapy.

PURPOSE: Male infertility caused by hypogonadotropic hypogonadism (HH) is not common. The main treatment is gonadotropins for 12 months or longer. If the patient is still azoospermic, conventional or microdissection testicular sperm extraction (mTESE) may further help in sperm retrieval. We aimed to analyze the fertility outcomes of HH men treated at our institute. METHODS: From 2008 to 2020, infertile men with hormone profile showing HH were enrolled. Gonadotropin therapy was prescribed if parenthood was being considered. Assisted reproductive technology was available to help patients attain fertility depending on the results of sperm analysis. Patient outcomes, including sperm retrieval, pregnancy and live birth rates, were analyzed. RESULTS: Seventeen initially azoospermic patients were administered gonadotropins for an average of 11.1 months, and sperm was subsequently found in the ejaculate of seven patients (41%). mTESE was performed on the other ten (59%) who were still azoospermic. For these 10 patients, they had collectively undergone an average 12.1 months (range 6-23 months) of gonadotropin therapy. Sperm was retrieved in nine (90.0%) cases. After 11 cycles of TESE-ICSI, six (54.5%) successful pregnancies were recorded, resulting in five (55.6%) cases with live-born babies, including two sets of twins, and one case of missed abortion at 9 weeks of gestation. CONCLUSION: Gonadotropin therapy reversed azoospermia in a portion of the HH male patients studied. Of men who were still azoospermic after gonadotropin treatment, a majority could still have testicular sperm retrieved by mTESE for use in assisted reproductive technology, subsequently resulting in live births.

Long Term Outcome of Postoperative Atrial Fibrillation After Cardiac Surgery-A Propensity Score-Matched Cohort Analysis.

Background: Postoperative atrial fibrillation (POAF) results in a longer hospital stay and excess mortality. However, whether POAF would increase stroke rate has been debated for years. When and how long should anticoagulation be used to prevent stroke are unknown. In the study, we planned to investigate the clinical demographics and long-term outcomes of POAF after cardiac surgery in a single-center cohort. Methods: The cohort study used a database from National Taiwan University Hospital, a single tertiary medical center in Taiwan, between 2007 and 2017, to identify patients with prior normal sinus rhythm developing POAF after cardiac surgery. Patients without POAF after cardiac surgery were used as controls. Propensity score matching with 1:1 ratio and Cox regression models were employed to estimate the risk of transient ischemic accident (TIA) or ischemic stroke. Results: From 2007 to 2017, a total of 8,374 patients received open-heart surgery, in which 1,585 patients with a history of AF were excluded. The overall incidence of TIA/ischemic stroke was 3.9% in a median 9.2-years of follow-up. After propensity matching, 1,965 matched paired subjects were included for analysis. Postoperative atrial fibrillation was associated with an increased risk of future AF [Hazard ratio (HR) 1.40, 95% confidence interval (95%CI) = 1.09-1.79, p = 0.008] and heart failure (HF) hospitalization (HR 1.58, 95%CI 1.23-2.04, p < 0.001); however, POAF did not significantly correlate with the risk of TIA/ischemic stroke (HR 1.17, 95%CI 0.85-1.60, p = 0.043). Kaplan-Meier analysis showed that POAF was a significant predictor for future AF, HF hospitalization, and overall mortality, but not for TIA/ischemic stroke. Conclusion: In the Asian population, POAF after cardiac surgery increased the risk of future AF, HF, and overall mortality, but was not associated with future TIA/ischemic stroke.

Developing a Web-Based Shared Decision-Making Tool for Fertility Preservation Among Reproductive-Age Women With Breast Cancer: An Action Research Approach.

BACKGROUND: The pregnancy rate after cancer treatment for female survivors is lower than that of the general population. Future infertility is a significant concern for patients with breast cancer and is associated with a poor quality of life. Reproductive-age patients with breast cancer have safe options when choosing a type of fertility preservation method to be applied. Better information and support resources aimed at women to support their decision making are needed. OBJECTIVE: The objective of this study was to develop a web-based shared decision-making tool for helping patients with breast cancer make decisions on fertility preservation. METHODS: We used the action research cycle of observing, reflecting, planning, and acting to develop a web-based shared decision-making tool. The following four phrases were applied: (1) observe and reflect-collect and analyze the decision-making experiences of patients and health care providers; (2) reflect and plan-apply the initial results to create a paper design and modify the content; (3) plan and act-brainstorm about the web pages and modify the content; (4) act and observe-evaluate the effectiveness and refine the website's shared decision-making tool. Interviews, group meetings, and constant dialogue were conducted between the various participants at each step. Effectiveness was evaluated using the Preparation for Decision-Making scale. RESULTS: Five major parts were developed with the use of the action research approach. The Introduction (part 1) describes the severity of cancer treatment and infertility. Options (part 2) provides the knowledge of fertility preservation. The shared decision-making tool was designed as a step-by-step process (part 3) that involves the comparison of options, patient values, and preferences; their knowledge regarding infertility and options; and reaching a collective decision. Resources (part 4) provides information on the hospitals that provide such services, and References (part 5) lists all the literature cited in the website. The results show the web-based shared decision-making meets both patients' and health providers' needs and helps reproductive-age patients with breast cancer make decisions about fertility preservation. CONCLUSIONS: We have created the first web-based shared decision-making tool for making fertility preservation decisions in Taiwan. We believe female patients of reproductive age will find the tool useful and its use will become widespread, which should increase patient autonomy and improve communication about fertility preservation with clinicians. TRIAL REGISTRATION: Clinicaltrials.gov NCT04602910; https://clinicaltrials.gov/ct2/show/NCT04602910.

Effects on skin dose from unwanted air gaps under bolus in an MR-guided linear accelerator (MR-linac) system.

Bolus is commonly used in MV photon radiotherapy to increase superficial dose and improve dose uniformity for treating shallow lesions. However, irregular patient body contours can cause unwanted air gaps between a bolus and patient skin. The resulting dosimetric errors could be exacerbated in MR-Linac treatments, as secondary electrons generated by photons are affected by the magnetic field. This study aimed to quantify the dosimetric effect of unwanted gaps between bolus and skin surface in an MR-Linac. A parallel-plate ionization chamber and EBT3 films were utilized to evaluate the surface dose under bolus with various gantry angles, field sizes, and different air gaps. The results of surface dose measurements were then compared to Monaco 5.40 Treatment Planning System (TPS) calculations. The suitability of using a parallel-plate chamber in MR-Linac measurement was validated by benchmarking the percentage depth dose and output factors with the microDiamond detector and air-filled ionization chamber measurements in water. A non-symmetric response of the parallel-plate chamber to oblique beams in the magnetic field was characterized. Unwanted air gaps significantly reduced the skin dose. For a frontal beam, skin dose was halved when there was a 5 mm gap, a much larger difference than in a conventional linac. Skin dose manifested a non-symmetric pattern in terms of gantry angle and gap size. The TPS overestimated skin dose in general, but shared the same trend with measurement when there was no air gap, or the gap size was larger than 5 mm. However, the calculated and measured results had a large discrepancy when the bolus-skin gap was below 5 mm. When treating superficial lesions, unwanted air gaps under the bolus will compromise the dosimetric goals. Our results highlight the importance of avoiding air gaps between bolus and skin when treating superficial lesions using an MR-Linac system.

Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and multiple small subcapsular cystic follicles in the ovary during ultrasonography, and affects 5-10% of women of reproductive age. PCOS is frequently associated with insulin resistance (IR) accompanied by compensatory hyperinsulinemia and, therefore, presents an increased risk of type 2 diabetes mellitus (DM). The pathophysiology of PCOS is unclear, and many hypotheses have been proposed. Among these hypotheses, IR and hyperandrogenism may be the two key factors. The first line of treatment in PCOS includes lifestyle changes and body weight reduction. Achieving a 5-15% body weight reduction may improve IR and PCOS-associated hormonal abnormalities. For women who desire pregnancy, clomiphene citrate (CC) is the front-line treatment for ovulation induction. Twenty five percent of women may fail to ovulate spontaneously after three cycles of CC treatment, which is called CC-resistant PCOS. For CC-resistant PCOS women, there are many strategies to improve ovulation rate, including medical treatment and surgical approaches. Among the various surgical approaches, one particular surgical method, called laparoscopic ovarian drilling (LOD), has been proposed as an alternative treatment. LOD results in an overall spontaneous ovulation rate of 30-90% and final pregnancy rates of 13-88%. These benefits are more significant for women with CC-resistant PCOS. Although the intra- and post-operative complications and sequelae are always important, we believe that a better understanding of the pathophysiological changes and/or molecular mechanisms after LOD may provide a rationale for this procedure. LOD, mediated mainly by thermal effects, produces a series of morphological and biochemical changes. These changes include the formation of artificial holes in the very thick cortical wall, loosening of the dense and hard cortical wall, destruction of ovarian follicles with a subsequently decreased amount of theca and/or granulosa cells, destruction of ovarian stromal tissue with the subsequent development of transient but purulent and acute inflammatory reactions to initiate the immune response, and the continuing leakage or drainage of "toxic" follicular fluid in these immature and growth-ceased pre-antral follicles. All these factors contribute to decreasing local and systemic androgen levels, the following apoptosis process with these pre-antral follicles to atresia; the re-starting of normal follicular recruitment, development, and maturation, and finally, the normalization of the "hypothalamus-pituitary-ovary" axis and subsequent spontaneous ovulation. The detailed local and systematic changes in PCOS women after LOD are comprehensively reviewed in the current article.

Endometriosis of the Paralumbar Muscles: A Case Report and Literature Review.

The objective of this study is to report a case of deep endometriosis of the paralumbar muscles (psoas, multifidus, and erector spinae) and review existing literature on its management. A 34-year-old female with a history of endometriosis was seen for infertility. Paralumbar muscle masses seen on computed tomography (CT) scan were sampled, confirming endometriosis. Gonadotropin-releasing hormone agonist was given for 2 months. The patient was primed for assisted reproduction. A literature review was conducted to provide an understanding of paralumbar muscle endometriosis. To our knowledge, this is the first reported case of multifidus and erector spinae muscle endometriosis and fifth case of psoas muscle endometriosis. Because the available information is scarce, data from the existing literature on deep endometriosis may aid in the diagnosis and management. Magnetic resonance imaging and CT scan are essential imaging techniques to map lesions. Excision seems prudent, but the approach should be individualized depending on the patient's presentation and her preferences.