Heat Shock Factor 1 Inhibition: A Novel Anti-Cancer Strategy with Promise for Precision Oncology.

Heat shock factor 1 (HSF1) is a transcription factor crucial for regulating heat shock response (HSR), one of the significant cellular protective mechanisms. When cells are exposed to proteotoxic stress, HSF1 induces the expression of heat shock proteins (HSPs) to act as chaperones, correcting the protein-folding process and maintaining proteostasis. In addition to its role in HSR, HSF1 is overexpressed in multiple cancer cells, where its activation promotes malignancy and leads to poor prognosis. The mechanisms of HSF1-induced tumorigenesis are complex and involve diverse signaling pathways, dependent on cancer type. With its important roles in tumorigenesis and tumor progression, targeting HSF1 offers a novel cancer treatment strategy. In this article, we examine the basic function of HSF1 and its regulatory mechanisms, focus on the mechanisms involved in HSF1's roles in different cancer types, and examine current HSF1 inhibitors as novel therapeutics to treat cancers.

Iron metabolism and ferroptosis: A pathway for understanding preeclampsia.

Preeclampsia (PE) is a serious medical condition that poses a significant health risk to women and children worldwide, particularly in the middle- and low-income countries. It is a complex syndrome that occurs as a result of abnormal pregnancy. Hypertension is the most common symptom of PE, with proteinuria and specific organ systems as detrimental targets. PE's pathogenesis is diverse, and its symptoms can overlap with other diseases. In early pregnancy, when the placenta takes over control, oxidative stress may be closely associated with ferroptosis, a type of cell death caused by intracellular iron accumulation. Ferroptosis in the placenta is defined by redox-active iron availability, loss of antioxidant capacity and phospholipids containing polyunsaturated fatty acids (PUFA) oxidation. Recent studies suggest a compelling potential link between ferroptosis and PE. In this article, we comprehensively review the current understanding of PE and discuss one of its emerging underlying mechanisms, the ferroptosis pathway. We also provide perspective and analysis on the implications of this process in the diagnosis, prevention, and treatment of preeclampsia. We aim to bridge the gap between clinicians and basic scientists in understanding this harmful disease and challenge the research community to put more effort into this exciting new area.

Uterine conservative-resective surgery for selected placenta accreta spectrum cases: Surgical-vascular control methods.

INTRODUCTION: The incidence of placenta accreta spectrum (PAS) has increased, but the optimal management and the optimal way to achieve vascular control are still controversial. This study aims to compare maternal outcomes between different methods of vascular control in surgical PAS management. MATERIAL AND METHODS: A retrospective cohort study on consecutive cases diagnosed with PAS between 2013 and 2020 in single tertiary hospital. The final diagnosis of PAS was made following preoperative ultrasound and confirmation during surgery. Management of PAS using cesarean hysterectomy with internal iliac artery ligation (IIAL) was compared with two types of vascular control in uterine conservative-resective surgery (IIAL vs identification-ligation of the upper vesical, upper vaginal, and uterine arteries). RESULTS: Over an 8-year period, 234 pregnant women were diagnosed with PAS meeting the inclusion criteria. Uterine conservative-resective surgery (200 cases) was associated with lower mean blood loss compared with cesarean hysterectomy with IIAL (34 cases) in all PAS cases (1379 ± 769 mL vs 3168 ± 1916 mL; p < 0.001). In sub-analysis of the two uterine conservative-resective surgery subgroups, the group with identification-ligation of the upper vesical, upper vaginal, and uterine arteries had a significantly lower blood loss compared with uterine conservative-resective surgery with IIAL (1307 ± 743 mL vs 1701 ± 813 mL; p = 0.005). Women in the hysterectomy with IIAL group had more massive transfusion (35.3% vs 2.5%; p < 0.001; odds ratio [OR] 21.3, 95% confidence interval [CI] 6.9-66), major blood loss (>1500 mL) (70.6% vs 34%, p < 0.001; OR 4.7; 95% CI 2.1-10.3), catastrophic blood loss (>2500 mL) (64.7% vs 12.5%;p < 0.001; OR 12.8, 95% CI 5.7-29.1), other complications (32% vs 12.4%; p = 0.007; OR 3.4, 95% CI 1.5-7.7), and intensive care unit admission (32.4% vs 1.5%; p < 0.001; OR 31.4, 95% CI 8.2-120.7) compared with the uterine conservative-resective surgery groups. The identification-ligation of the upper vesical, upper vaginal and uterine arteries had a significant lower risk for major blood loss (30.5% vs 50%; p = 0.041; OR 0.44, 95% CI = 0.2-0.9) compared with IIAL for vascular control of uterine conservative-resective surgery. CONCLUSIONS: Cesarean hysterectomy is not the default treatment for PAS, PAS with invasion above the vesical trigone are suitable for uterine conservative-resective surgery with upper vesical, upper vaginal and uterine artery vascular control.

Clinical manifestations and pregnancy outcomes of COVID-19 in indonesian referral hospital in central pandemic area.

OBJECTIVE: s Data on the clinical manifestations and pregnancy outcomes of pregnant women with COVID-19 are limited, particularly in developing countries. The aim of this study was to analyze the clinical manifestations and pregnancy outcomes in COVID-19 maternal cases in a large referral hospital in Indonesia. METHODS: This study used a prospective cohort design and included all pregnant women with suspected COVID-19. Subjects were divided into COVID-19 and non-COVID-19 groups based on the results of real-time polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2. Clinical characteristics, laboratory results, and pregnancy outcomes were compared between the two groups. RESULTS: Of the 141 suspected maternal cases, 62 cases were COVID-19-confirmed (43.9%), while 79 suspected cases were negative (56.1%). The clinical manifestations and laboratory findings between the two groups were not significantly different (P>0.05). However, the maternal mortality directly caused by COVID-19 was significantly higher than that in the non-COVID-19 group (8.3% vs. 1.3%; P=0.044; odd ratio, 6.91; 95% confidence interval, 0.79-60.81). CONCLUSION: The clinical manifestations and laboratory results of suspected pregnant women with positive and negative RT-PCR COVID-19 results were similar. However, within the Indonesian setting, COVID-19 significantly increases the risk of maternal death through both direct and indirect factors.

Successful management of a pregnant woman with COVID-19 and multiple severe complications.

We report a case of a 36-year-old gravida 2 para 1 woman at 38 weeks of gestation. A caesarean section was performed for severe pre-eclampsia, intrauterine growth restriction and oligohydramnios. The patient suffered postoperative bleeding, and exploratory laparotomy was performed. Uterine atonia, Couvelaire uterus and left adnexal haematoma were found, requiring a supracervical hysterectomy. As COVID-19 pneumonia and superimposed bacterial infection developed, the patient was mechanically ventilated in the intensive care unit. Remdesivir and meropenem were initially administered, but were changed to levofloxacin and ciprofloxacin following antibiotic sensitivity tests. Blood culture grew Enterococcus galinarum Meanwhile, bleeding of the incisional wound occurred, which was controlled by the cessation of heparin therapy and regular wound care. With intensive monitoring and multidisciplinary management, the patient's condition improved, and she was discharged from the hospital on day 25 from admission.

INA-CBGs claim versus total hospital cost: A vaginal delivery investigation at Airlangga University Academic Hospital, Indonesia.

Background: Inadequate funding for vaginal delivery can be one of the barriers to reducing the maternal mortality rate. It could be therefore critical to compare the vaginal delivery cost between total hospital cost and INA-CBGs cost in national health insurance. Methods: This was a retrospective cross-sectional study conducted from October to December 2019 in Universitas Airlangga Academic Hospital. It collected data on primary diagnosis, length of stay, total hospital cost, INA-CBGs cost, and counted disparity. The data analyzed statistically using t-test independent sample (or Mann-Whitney test). Results: A total of 149 vaginal delivery claims were found, with the majority having a level II severity (79.87%) and moderate preeclampsia as a primary diagnosis (20.1%). There was a significant disparity in higher total hospital costs compared with government INA-CBGs costs (Rp. 9,238,022.09±1,265,801.88 vs 1,881,521.48±12,830.15; p<0.001). There was also an increase of LOS (p<0.001), total hospital cost (p<0.001), and cost disparity (p<0.01) in a higher severity level of vaginal delivery. Conclusion: Vaginal delivery costs in INA-CBGs scheme are underneath the actuarial value. There was also an increase in total hospital costs and a more significant disparity in the higher severity levels of vaginal delivery.

New three-dimensional/four-dimensional volume rendering imaging software for detecting the abnormally invasive placenta.

OBJECTIVE: This study aimed to determine the role of three-dimensional (3D)/four-dimensional (4D) volume rendering ultrasound (VRU) in the diagnosis of abnormally invasive placenta (AIP). MATERIALS AND METHODS: Twelve consecutive patients strongly suspected of having AIP on the basis of conventional ultrasound (US) and clinical history performed between September 2016 and December 2016 in the main tertiary referral hospital in Surabaya, East Java were included in this prospective observational study. A Samsung WS 80A Elite US scanner with a 3D/4D "crystal vue" and "realistic vue" volume rendering mode was used to establish the diagnosis of AIP and evaluate the site, and depth of placental invasion. The VRU images were compared with the intraoperative findings. RESULTS: Using this novel US technique, all cases of suspected AIP were subsequently confirmed during surgery. Importantly, the new US technique provided a correct diagnosis of the degree of invasion in 11 out of these 12 suspected AIP cases: 5/5 for placenta percreta, 3/3 for placenta increta, and 2/3 for placenta accreta; one patient was misdiagnosed in terms of the degree of placenta accreta, and one patient had normal implantation). CONCLUSION: This new software of 3D/4D VRU represents a promising technique for the preoperative diagnosis and staging of AIP.

Serum heme oxygenase 1 (HO-1), soluble FMS like tyrosine kinase (sFlt-1) level, and neonatal outcome in early onset, late onset preeclampsia, and normal pregnancy.

OBJECTIVE: To compare the level of serum heme oxygenase 1 (HO-1), soluble FMS like tyrosine kinase (sFlt-1), and neonatal outcome in early onset preeclampsia (EO-PE), late onset preeclampsia (LO-PE), and normal pregnancy (NP). METHODS: In this prospective observational case control study, HO-1 and sFlt-1 levels were measured in blood samples within 24 h of hospital admission. Preeclampsia cases were divided into two groups based on gestational age at delivery: EO-PE (<34 weeks) and LO-PE (≥34 weeks). A total of 45 patients were involved in this study. RESULT: Maternal serum level of sFlt-1 was higher in EO-PE than LO-PE and NP groups (mean ± SD; 14.50 ± 17.12 ng/ml vs 5.20 ± 6.69 ng/ml vs 2.72 ± 1.2 ng/ml [p = 0.020]. Maternal serum level of HO-1 was not different between EO-PE, LO-PE, and NP groups (p = 0.681). Birthweights were significantly lower in the EO-PE group compared with the LO-PE and NP groups (1580 ± 536 g vs 2635 ± 578 g vs 3010 ± 371 g [p = 0.000]). The rate of small for gestational age infant (26.7% vs 6.7% vs 0%; p = 0.046) and perinatal death (20% vs 0 vs 0; p = 0.037) was also significantly higher in EO-PE compared to LO-PE and NP. The maternal sFlt-1 level was negatively correlated with birthweight (p = 0.006; CC = -0.445). CONCLUSION: This study did not find a correlation between maternal HO-1 levels and sFlt-1 levels. Maternal serum sFLt-1 levels in preeclampsia were higher in EO-PE and were associated with a worse perinatal outcome.