Focus on the Primary Prevention of Intrauterine Adhesions: Current Concept and Vision.

Intrauterine adhesion (IUA), and its severe form Asherman syndrome (Asherman's syndrome), is a mysterious disease, often accompanied with severe clinical problems contributing to a significant impairment of reproductive function, such as menstrual disturbance (amenorrhea), infertility or recurrent pregnancy loss. Among these, its correlated infertility may be one of the most challenging problems. Although there are many etiologies for the development of IUA, uterine instrumentation is the main cause of IUA. Additionally, more complicated intrauterine surgeries can be performed by advanced technology, further increasing the risk of IUA. Strategies attempting to minimize the risk and reducing its severity are urgently needed. The current review will expand the level of our knowledge required to face the troublesome disease of IUA. It is separated into six sections, addressing the introduction of the normal cyclic endometrial repairing process and its abruption causing the formation of IUA; the etiology and prevalence of IUA; the diagnosis of IUA; the classification of IUA; the pathophysiology of IUA; and the primary prevention of IUA, including (1) delicate surgical techniques, such as the use of surgical instruments, energy systems, and pre-hysteroscopic management, (2) barrier methods, such as gels, intrauterine devices, intrauterine balloons, as well as membrane structures containing hyaluronate-carboxymethylcellulose or polyethylene oxide-sodium carboxymethylcellulose as anti-adhesive barrier.

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 Might Be Inversely Associated with Developing Chronic Kidney Disease: A Population-Based Cohort Study in Taiwan.

This study was conducted to determine the risk of chronic kidney disease (CKD) among women with endometriosis in Taiwan. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan. A total of 27,973 women with a diagnosis of endometriosis and 27,973 multivariable-matched controls (1:1) from 2000 to 2010 were selected. Cox regression and computed hazard ratios (HR) with 95% confidence intervals (95% CI) were used to determine the risk of CKD among women with endometriosis. The incidence rates (IR, per 10,000 person-years) of CKD among women with and without endometriosis were 4.64 and 7.01, respectively, with a significantly decreased risk of CKD (crude HR 0.65, 95% CI 0.53-0.81; adjusted HR 0.69, 95% CI 0.56-0.86) among women with endometriosis. The IR of CKD progressively increased with age, but the trend of lower CKD risk among women with endometriosis was consistent. However, the lower risk of CKD in women with endometriosis was no longer statistically significant after adjusting for menopausal status (adjusted HR 0.85, 95% CI 0.65-1.10). The results suggest that endometriosis is inversely associated with CKD, but this effect was mediated by menopause. The possible mechanism of this association is worthy of further evaluation.

An increased risk of epithelial ovarian cancer in Taiwanese women with a new surgico-pathological diagnosis of endometriosis.

BACKGROUND: Epidemiological evidence of relationships between endometriosis and epithelial ovarian cancer (EOC) has been obtained mainly from Western countries. Our goal was to determine the risk of EOC due to endometriosis in Taiwanese women. METHODS: A retrospective cohort study was performed by linking to the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 5,945 women with a new surgico-pathological diagnosis of endometriosis from 2000 to 2010 and 23,780 multivariable-matched controls (1:4) were selected. The Cox regression model adjusted for potential confounders was used to assess the risk of EOC due to endometriosis. RESULTS: The EOC incidence rate (IR) of the women with and without endometriosis was 11.64 and 2.66 per 10,000 person-years, contributing to a crude hazard ratio (HR) of 4.48 (95% confidence interval [CI] 2.84-7.06), and HR after adjustment for all confounders (adjusted HR) of 5.62 (95% CI 3.46-9.14); the risk was higher in clear-cell carcinoma subtypes (adjusted HR 7.36, 95% CI 1.91-28.33). The EOC IR of women with endometriosis consistently increased with increasing age, ranging from 4.99 (<30 years) to 35.81 (≥50 years) per 10,000 person-years, contributing to a progressively increased risk of EOC (crude HRs ranging from 2.80 to 6.74 and adjusted HRs ranging from 3.34 to 9.63) compared to age-matched women without endometriosis, whose EOC IR also increased with age. The older women (≥50 years) with endometriosis had a risk of EOC that was higher than both the age-matched women without endometriosis (adjusted HR 9.63, 95% CI 3.27-28.37) and the youngest women (<30 years) with endometriosis (adjusted HR 4.97, 95% CI 1.03-24.09). CONCLUSIONS: These significant findings corroborate the previously reported association between endometriosis and increased risk of EOC. Since the risk of EOC in women with a new surgico-pathological diagnosis of endometriosis constantly increased with age and this increased risk of EOC was more significant in women aged ≥50 years, active and intensive surgical intervention should be taken into consideration for older women with endometriosis.

Cervical cancer: Part II the landscape of treatment for persistent, recurrent and metastatic diseases (I).

The WHO (World Health Organization) conducted an elimination of cervical cancer program using triple pillar intervention strategy to target 90%-70%-90% of women before the year 2030, including (1) a full vaccination of HPV (human papillomavirus) vaccine to 90% of girls <15 years of age; (2) a high-performance screening procedure to 70% of women during the reproductive age (at the age of 35 and 45 years of age); and (3) an appropriate and adequate treatment to 90% of women with confirmed diagnosis of cervical lesions. Among the aforementioned three pillars, a full HPV vaccination has been introduced in our previous review, of which we have discussed the policy and strategy of HPV vaccination in the world and also reviewed the efficacy of HPV vaccination, with a successful reduction of over 90% of HPV-associated neoplasms. The aims of the current review will target another pillar-an appropriate and adequate treatment to 90% of women with confirmed diagnosis of cervical lesions. Since the early-stage cervical cancer has a favorable outcome and the treatment recommendation has been established, therefore, the current review focuses on women with persistent, recurrent and metastatic cervical cancers (advanced cervical cancers), which are still a biggest challenge based on its extremely worse outcomes before the introduction of immune checkpoint inhibitors (ICIs). Integration of ICIs into conventional chemotherapy (paclitaxel-cisplatin) has become the new standard therapy for those patients with advanced cervical cancers. The recent clinical trials, such as KENOTE 826 and KENOTE A18 showing a dramatical improvement of both progression free survival and overall survival have approved the therapeutic efficacy of this combination as ICI plus paclitaxel-platinum (cisplatin or carboplatin) with/without bevacizumab to women with persistent, recurrent and metastatic cervical cancers.

Surgery-based radiation-free multimodality treatment for locally advanced cervical cancer.

The current review described a 55-year woman using 28 months to finish her surgery-based radiation-free multimodality treatment journey to fight International Federation of Gynaecology & Obstetrics (FIGO) 2018 clinical stage IIA2 (cT2aN0M0) squamous cell carcinoma (SCC) of the cervix. She received six cycles of perioperative adjuvant therapy, including three cycles of neoadjuvant therapy (NAT) and three cycles of postoperative adjuvant therapy by using combination of dose-dense chemotherapy (CT, weekly paclitaxel 80 mg/m2+triweekly cisplatin 40 mg/m2), immunotherapy (IO, triweekly pembrolizumab 200 mg) and half-dose anti-angiogenic agent (triweekly bevacizumab 7.5 mg/kg) plus interval radical surgery (radical hysterectomy + bilateral salpingo-oophorectomy + bilateral pelvic lymph node dissection + para-aortic lymph node sampling) and following maintenance therapy with monthly 22 cycles of half-dose of IO (pembrolizumab 100 mg) and concomitant 4 cycles of single-agent CT (paclitaxel 175 mg/m2) and 18 cycles of half-dose anti-angiogenic agent (bevacizumab 7.5 mg/kg). During the cervical SCC fighting journey, two unwanted adverse events (AEs) occurred. One was pseudo-progressive disease during the NAT treatment and pathology-confirmed upgrading FIGO stage IIIC1p (ypT2a1N1M0) after radical surgery and the other was the occurrence of hypothyroidism during the post operative adjuvant therapy. Based on this case we presented, we review the recent trend in the management of women with locally advanced cervical cancer (LACC) using the radiation-free but surgery-based multimodality strategy and highlight the strengths and limitations about perioperative adjuvant therapy with dose-dense CT + IO + half-dose anti-angiogenic agent and maintenance treatment of half-dose IO combining with short-term single agent CT and following long-term half-dose anti-angiogenic agent. All underscore the possibility that women with LACC have an opportunity to receive surgery-based RT-free multi-modality strategy to manage their diseases with satisfactory results. Additionally, the evolving role of IO plus CT with/without anti-angiogenic agent functioning as either primary treatment or adjuvant therapy for the treatment of advanced CC has been in process continuously. Moreover, the patient's positive response to IO, pembrolizumab as an example, both during the primary and maintenance therapy, highlights the importance of integrating IO into CT regimens for CC, especially in cases where conventional therapies, RT as an example, are insufficient or who do not want to receive RT-based treatment. The sustained disease-free status of the patient over several years reinforces the potential of IO to significantly increase long-term survival outcomes in CC patients, particularly for those with LACC.

Intrauterine adhesion.

Intrauterine adhesions (IUA) occurred in the reproductive-age women are a big economic and health problem, resulting in severe impairment of social, psychological and physical function of the female genital organs. IUA-related symptoms or signs are varied greatly from free of symptoms or ambiguous symptoms (an incidental finding during the intervention) to ceased menstruation and loss of fecundability. The underlying pathophysiology is not completely understood, but intrauterine damage with broken basal layers of the endometrium formatting scar tissues or fibrosis in the endometrium with subsequently causing partial or complete occlusion of the uterine cavity may be a well-accepted hypothesis. Previously, infection is the most common cause to develop IUA, but now, intrauterine surgery may be a critical cause contributing to the majority of cases of IUA. In the current review, update information about the etiology, epidemiology, pathophysiology, sequelae and prevention of IUA will be renewed. We emphasize the importance of awareness of IUA, and primary prevention should be considered in the routine clinical practice if intrauterine surgery has been applied, based on uncertainty of ideal treatment for the established IUA and unpredictable outcomes after IUA treatment. So far, evidence supports that hyaluronic acid with/without other strategy is the most valuable and effective method to reduce the formation and re-formation of IUA as well as to achieve the best fertility outcome.

Cervical cancer: Part I human papilloma virus vaccination in Taiwan.

A significant decline in both incidence and prevalence of cervical cancers after widespread-introducing cervical screening strategy by Papanicolau test (Pap test) has been found in the world, but cervical cancer is still one of the most common female cancers, reporting the fourth prevalence and also one of the leading causes to result in main women-associated morbidity and mortality, particularly for those women living in low- and middle-income countries. Cervical cancer is one of the most important health concerns directly destroying the global health-care system, partly because of not only increasing the disability either secondary to diseases themselves of victims or mediated by treatment-related adverse events to the survivors but also acting as a leading cause of death of diseased patients worldwide, alarming the urgent need to do something to minimize the catastrophic diseases-related heavy socioeconomic burden. It is fortunate that cervical cancer is a preventable disease, based on its strong association with human papillomavirus (HPV) infection (more than 95%), particularly for those high-risk HPV (HR-HPV) and its high possibility by detecting HPV infection before the development of cervical cancer as well as an effective prevention by HPV vaccination. That is why WHO (World Health Organization) considers cervical cancer as a public problem and attempts to accelerate the elimination of cervical cancer program by three-pillar approach (90:70:90% targets), including (1) 90% of girls are fully vaccinated with HPV vaccine by 15 years of age; (2) 70% of women are screened with a high-performance test by 35 and 45 years of age and precancerous lesions are treated early; and (3) 90% of women identified with cervical diseases receive appropriate and adequate treatment. Herein, this review focuses on the HPV vaccination as Part I, including global recommendations and Taiwan government's policy for HPV vaccination.

Front-line chemoimmunotherapy for treating epithelial ovarian cancer: Part II promising results of phase 2 study of paclitaxel-carboplatin-oregovomab regimen.

In the Part I, we have discussed the background of CA125 and the development of anti-CA125 monoclonal antibody (MAb) to highlight the potential role of CA125 and anti-CA125 MAb in the management of women with advanced stage epithelial ovarian cancer (EOC). Glycosylation change either by N-link or by O-link of CA125 is supposed to play a role in the modification of immunity. Anti-CA125 MAb, which can be classified as OC 125-like Abs, M11-like Abs, and OV197-like Abs, is often used for diagnosing, screening, monitoring and detecting the mesothelin-related diseases of the abdominal cavity, particular for those women with EOC. Additionally, anti-CA125 MAb also plays a therapeutic role, named as OvaRex MAb-B43.13 (oregovomab), which has also been extensively reviewed in the Part I review article. The main mechanisms include (a) forming CA125 immune complexes to activate the antigen-presenting cells; (b) triggering induction of CA125-specific immune responses, including anti-CA125 Abs against various epitopes and CA125-specific B and T cell responses; and (c) triggering CD4 and CD8 T-cell responses specific for B43.13 to produce specific and non-specific immune response. With success in vitro, in vivo and in primitive studies, phase II study was conducted to test the effectiveness of chemoimmunotherapy (CIT) for the management of EOC patients. In the 97 EOC patients after optimal debulking surgery (residual tumor <1 cm or no gross residual tumor), patients treated with CIT had a dramatical and statistically significant improvement of both progression-free survival (PFS) and overall survival (OS) compared to those treated with chemotherapy alone with a median PFS of 41.8 months versus 12.2 months (hazard ratio [HR] 0.46, 95 % confidence interval [CI] 0.28-0.7) and OS not yet been reached (NE) versus 42.3 months (HR 0.35, 95 % CI 0.16-0.74), respectively. The current review as Part II will explore the possibility of using CIT as front-line therapy in the management of advanced-stage EOC patients after maximal cytoreductive surgery based on the evidence by many phase 2 studies.

The role of sialylation in gynecologic cancers.

Sialic acids (SA) are a kind of nine-carbon backbone sugars, serving as important molecules in cell-to-cell or cell-to-extra-cellular matrix interaction mediated by either O-linked glycosylation or N-linked glycosylation to attach the terminal end of glycans, glycoproteins, and glycolipids. All processes need a balance between sialylation by sialyltransferase (STs) and desialylation by sialidases (also known as neuraminidases, NEU). Although there is much in uncertainty whether the sialyation plays in cancer development and progression, at least four mechanisms are proposed, including surveillance of immune system, modification of cellular apoptosis and cell death, alteration of cellular surface of cancer cells and tumor associated microenvironment responsible carcinogenesis, growth and metastases. The current review focuses on the role of glycosylation in gynecologic organ-related cancers, such as ovarian cancer, cervical and endometrial cancer. Evidence shows that sialylation involving in the alternation of surface components of cells (tumor and cells in the microenvironment of host) plays an important role for carcinogenesis (escape from immunosurveillance) and dissemination (metastasis) (sloughing from the original site of cancer, migration into the circulation system, extravasation from the circulatory system to the distant site and finally deposition and establishment on the new growth lesion to complete the metastatic process). Additionally, modification of glycosylation can enhance or alleviate the aggressive characteristics of the cancer behaviors. All suggest that more understandings of glycosylation on cancers may provide a new therapeutic field to assist the cancer treatment in the near future.

Front-line chemo-immunotherapy for treating epithelial ovarian cancer: Part I CA125 and anti-CA125.

The current standard therapy of epithelial ovarian cancer (EOC) is the combination of surgery (primary cytoreductive surgery or interval cytoreductive surgery) and platinum-based chemotherapy (mainly using paclitaxel and carboplatin either by neoadjuvant chemotherapy and/or by postoperative adjuvant chemotherapy) with/without adding targeted therapy (mainly using anti-angiogenesis agent- bevacizumab). After front-line chemotherapy, the advanced-stage EOC can be successfully controlled and three-quarters of patients can achieve a complete clinical remission. Unfortunately, nearly all patients will recur and progression-free survival (PFS) of these patients is seldom more than 3 years with a dismal median PFS of 12-18 months. With each recurrence, patients finally develop resistance to standard chemotherapy regimen, contributing to fewer than half of women who survive for more than 5 years after diagnosis with a median overall survival (OS) of 40.7 months. Due to the lower PFS and OS, particularly for those advanced-stage patients, novel therapeutic options during the front-line therapy are desperately needed to decrease the occurrence of recurrence, and the majority of them are still under investigation. It is well-known that overexpression of CA125 has been associated with attenuated cellular apoptosis, platinum chemotherapy resistance, tumor proliferation and disease progression, suggesting that anti-CA125 may play a role in the management of patients with EOC. The current review is a Part I which will focus on development of anti-CA125 monoclonal antibody, hoping that alternation of the front-line therapy by chemo-immunotherapy will be beneficial for prolonged survival of patients with EOC.

Endometriosis: Part I. Basic concept.

Endometriosis, manifested by pain and infertility, is a chronic inflammatory disease, associated with a large disability of daily living, causing a socio-economic diastrophic problem and burden. The main goal of therapy attempts to reduce pain, correct infertility and possibly avoid or delay occurrence of long-term endometriosis-associated sequelae, such as fibrosis, adhesion and malignant transformation. Although the advanced technology (minimally invasive diagnostic tools, magnetic resonance imaging, high-resolution vaginal ultrasound etc.) and the better understanding pathophysiology of endometriosis for development of new therapeutic strategy is continuous for both diagnosis and management of endometriosis, there is still presence of many debated issues, which commonly occur in routine clinical practice. For example, the timing and duration of medications may be one of most frequently discussed issues. In this part I, we would like to overview the general background knowledge (basic concept) about the endometriosis, and emphasize the role of clinical diagnosis and possible empirical medical treatment (therapeutic test) for the management of women with endometriosis.

Endometrial cancer: Part I. Basic concept.

Endometrial cancer (EC) has become one of rapidly increasing women's cancers, contributing to the most common cancer of the female genital tract in high- and middle-incomed countries, including Taiwan. In general, EC is believed its favorable outcome; however, high-grade endometrial cancers have a tendency to recur and also have a high risk to be presented as an advanced stage or accompanied with metastatic lesions, which result in a biggest therapeutic challenge. The standard therapy includes complete staging surgery (sentinel node sampling)/optimal debulking surgery, and subsequent adjuvant therapy, by either radiotherapy locally or systemic therapy as chemotherapy or targeted therapy, or in combination or in subsequential strategy is made based on the risk stratification using clinicopathological prognostic factors. All efforts are made to minimize the risk of recurrence and possible therapeutic failure. In this part I, we would like to overview the general background knowledge (basic concept) about the cancer of uterine corpus, and discuss the recent transformation to patients-tailored therapy based on modern molecular technology as the optimal strategy to balance the therapeutic efficacy and treatment-related toxicity. Optimally, it is possible to reach the best benefits.

To do one and to get more: Part I. Diabetes and bone.

Type 2 diabetes mellitus (T2DM), is a chronic metabolic disease, characterized by the presence of hyperglycemia and insulin resistance. The key treatment strategies for T2DM include modification of lifestyle, medications, and continuous glucose monitoring. DM patients often have DM-associated morbidities and comorbidities; however, disorders of musculoskeletal system are often neglected, compared to other major systems in DM patients. Based on sharing similar pathophysiology of DM and osteoporosis, it is supposed that the use of antidiabetic agents (ADAs) may not only provide the lowering glucose level effect and the maintenance of the sugar homeostasis to directly delay the tissue damage secondary to hyperglycemia but also offer the benefits, such as the prevention of developing osteoporosis and fractures. Based on the current review, evidence shows the positive correlation between DM and osteoporosis or fracture, but the effectiveness of using ADA in the prevention of osteoporosis and subsequent reduction of fracture seems to be inconclusive. Although the benefits of ADA on bone health are uncertain, the potential value of "To do one and to get more" therapeutic strategy should be always persuaded. At least, one of the key treatment strategies as an establishment of healthy lifestyle may work, because it improves the status of insulin resistance and subsequently helps DM control, prevents the DM-related micro- and macrovascular injury, and possibly strengthens the general performance of musculoskeletal system. With stronger musculoskeletal system support, the risk of "fall" may be decreased, because it is associated with fracture. Although the ADA available in the market does not satisfy the policy of "To do one and to get more" yet, we are looking forward to seeing the continuously advanced technology of drug development on diabetic control, and hope to see their extra-sugar-lowering effects.

Association between Pre-Pregnancy Overweightness/Obesity and Pregnancy Outcomes in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Polycystic ovary syndrome (PCOS) is a common metabolic problem in women of reproductive age. Evidence suggests pregnant women with PCOS may have a higher risk of the development of adverse pregnancy outcomes; however, the relationship between pre-pregnancy overweight/obesity and pregnancy outcomes in women with PCOS remains uncertain. We try to clarify the relationship between pre-pregnancy overweight/obesity and subsequent pregnancy outcomes. Therefore, we conducted this systematic review and meta-analysis. We used the databases obtained from the PubMed, Embase, Web of Science, and Cochrane databases, plus hand-searching, to examine the association between pre-pregnancy overweightness/obesity and pregnancy outcomes in women with PCOS from inception to 4 February 2022. A total of 16 cohort studies, including 14 retrospective cohort studies (n = 10,496) and another two prospective cohort studies (n = 818), contributed to a total of 11,314 women for analysis. The meta-analysis showed significantly increased odds of miscarriage rate in PCOS women whose pre-pregnancy body mass index (BMI) is above overweight (OR 1.71 [95% CI 1.38-2.11]) or obese (OR 2.00 [95% CI 1.38-2.90]) under a random effect model. The tests for subgroup difference indicated the increased risk was consistent, regardless which body mass index cut-off for overweight (24 or 25 kg/m2) or obesity (28 and 30 kg/m2) was used. With the same strategies, we found that pregnant women in the control group significantly increased live birth rate compared with those pregnant women with PCOS as well as pre-pregnancy overweight/obesity (OR 0.79 [95% CI 0.71-0.89], OR 0.78 [95% CI 0.67-0.91]). By contrast, we did not find any association between PCOS women with pre-pregnancy overweight/obesity and preterm birth. Based on the aforementioned findings, the main critical factor contributing to a worse pregnancy outcome may be an early fetal loss in these PCOS women with pre-pregnancy overweight/obesity. Since PCOS women with pre-pregnancy overweightness/obesity were associated with worse pregnancy outcomes, we supposed that weight reduction before attempting pregnancy in the PCOS women with pre-pregnancy overweightness/obesity may improve the subsequent pregnancy outcomes.

To do one and to get more: Part II. Diabetes and metabolic dysfunction-associated fatty liver diseases.

Type 2 diabetes mellitus (DM) is characterized by inability of faulty pancreatic ß-cells to secret a normal amount of insulin to maintain normal body consumption, and/or peripheral tissue has a decreased susceptibility to insulin, resulting in hyperglycemia and insulin resistance. Similar to other chronic systemic inflammatory diseases, DM is a result from dysregulated interactions between ethnic, genetic, epigenetic, immunoregulatory, hormonal, and environmental factors. Therefore, it is rational to suppose the concept as "To do one and to get more", while using antidiabetic agents (ADA), a main pharmacologic agent for the treatment of DM, can provide an extraglycemia effect on comorbidities or concomittent comorbidities to DM. In this review, based on the much strong correlation between DM and metabolic dysfunction-associated fatty liver diseases (MAFLD) shown by similar pathophysiological mechanisms and a high prevalence of DM in MAFLD and its vice versa (a high prevalence of MAFLD in DM), it is possible to use the strategy to target both diseases simultaneously. We focus on a new classification of ADA, such as glucagon-like peptide-1 receptor (GLP1R) agonist and sodium-glucose cotransporter-2 (SGLT-2) inhibitors to show the potential benefits of extraglycemic effect on MAFLD. We conclude that the management of DM patients, especially for those who need ADA as adjuvant therapy should include healthy lifestyle modification to overcome the metabolic syndrome, contributing to the urgent need of an effective weight-reduction strategy. GLP1R agonist is one of effective body weight-lowering medications, which may be a better choice for DM complicated with MAFLD or its-associated severe form as metabolic associated steatohepatitis (MASH), although the role of SGLT-2 inhibitors is also impressive. The prescription of these two classes of ADA may satisfy the concept "To do one and to get more", based on successful sugar-lowering effect for controlling DM and extraglycemia benefits of hepatoprotective activity in DM patients.

Myomectomy for uterine myomas through ultramini-laparotomy.

Uterine fibroids are the most common benign tumors in the female reproductive tract during the reproductive years. Among the options in the treatment spectrum, myomectomy is always considered one of the best choices in the management of women with symptomatic uterine fibroids who wish to preserve future fertility. Myomectomy through conventional exploratory laparotomy may be the most familiar surgical approach. However, with the advances being made in techniques and instruments, there are many alternative approaches to myomectomy, including mini-laparotomy, ultramini-laparotomy, laparoscopy, laparoscopy-aided, and vaginal and hysteroscopic approaches. The focus of this review article is limited to discussing the use of the ultramini-laparotomy approach to completing myomectomy in the management of the uterine fibroids.

Special Issue "Reproductive Health Concerns for Women".

There are specific health issues concerning the reproductive age of women, including inflammatory disease, fertility, and childbearing [...].

The impact of COVID-19 in pregnancy: Part II. Vaccination to pregnant women.

Effective strategies are urgently needed to decrease the risk of untoward outcomes of pregnant women with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) infection. Pregnant women are a vulnerable population to infectious disease pandemics with dramatically increased infectious diseases-related serious complications, such as the need of hospitalizations, the need of admission to intensive care unit, and the final disease-related death compared with those nonpregnant counterparts or those pregnant women without infection. Several studies have shown that vaccinations in pregnancy are a safe and highly effective strategy, not only for pregnant women but also for fetus and/or newborn because of the passive transplacental transfer of antibodies to the offspring. Active and passive prevention of infectious diseases is approved as effective strategies for women who attempt to become pregnant or during pregnancy. Despite the large and proven scientific evidence, pregnant women still puzzle over whether they should get vaccinated. The question therefore arises: Why are pregnant women so reluctant to receive vaccination? The explanation is more likely in the way that the benefits of vaccination have been communicated "confusedly." In fact, like virtually all clinical trials, all the COVID-19 vaccine trials have excluded pregnant and lactating women from participating, contributing to uncertainty of safety and efficacy in COVID-19 vaccines that have been well prepared and available for the general adult population worldwide. Moreover, messenger RNA vaccine is a relatively brand-new vaccine, and experience with this type of vaccine is still scarce. It is hard to overcome this innovation deadlock. The knowledge and awareness of pregnant women who are at risk, and full information on the knowledge of vaccines and related preventable diseases in pregnant women may avoid hesitancy and increase vaccine acceptance. The current review is a part two addressing the impact of COVID-19 on pregnant women. We focus on the up-to-date information about the application of vaccination on pregnant women, especially during this COVID-19 pandemic.

The impact of COVID-19 in pregnancy: Part I. Clinical presentations and untoward outcomes of pregnant women with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019, COVID-19) is a pandemic disease with rapidly and widely disseminating to the world. Based on experiences about the H1N1, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) coronavirus pandemics, pregnant women who are infected are disproportionately more likely to develop severe illness and need more hospitalizations, intensive care, and finally die of diseases compared with those nonpregnant counterparts or those pregnant women without infection. Although more than one half of pregnant women with COVID-19 are asymptomatic, and as well as their symptoms are frequently mild, this observation presents a further challenge regarding service provision, prevention, and management, in which this may result in overlooking the risk of COVID-19 during pregnancy. As predictable, despite much advance in critical care in recent decades, during the 2020 COVID-19 pandemic, pregnant women with COVID-19 are really at higher risk to progress to severe illness; require hospitalization; need intensive care, such as the use of mechanical ventilation as well as extracorporeal membrane oxygenation (ECMO), and of most important, die than their nonpregnant counterparts and pregnant women without COVID-19. The magnitude of the risk to pregnant women further extend to their newborn from COVID-19 with resultant significantly increasing perinatal and neonatal morbidity and mortality rates. The heightened risk of untoward outcomes in pregnant women emphasizes an urgent need of national or international recommendations and guidelines to optimize prevention and management strategies for COVID-19 in pregnancy. Active and passive prevention of COVID-19 is approved as effective strategies for women who attempt to be pregnant or during pregnancy. Understanding that pregnant women who are a vulnerable population is essential to improve the care in the novel and urgent COVID-19 pandemic. The current review is a part I to summarize the up-to-date information about the impact of laboratory-confirmed SARS-CoV-2 infection on pregnant women and focus on clinical presentations and untoward pregnancy outcomes of these pregnant women infected with SARS-CoV-2.