Efficacy and Safety Profile of Tuberculin Protein Purified Derivative Injection As Immunotherapy For the Treatment of Cutaneous and Anogenital Warts: A Review Article.

Introduction: Various treatments available today for anogenital and cutaneous warts have limitations, including time-consuming, challenging to perform, and the risk of scarring. A new treatment using tuberculin purified protein derivative (PPD) has been developed, which is expected to generate cellular immunity against HPV. Objective: To assess the evidence for the efficacy and safety of PPD treatment for cutaneous and anogenital warts. Materials and methods: A literature search was performed with the keyword-based search on digital libraries, including the National Library of Medicine, Cochrane Controlled Register of Trial, and Google Scholar, using the following terms: anogenital warts, condyloma acuminata, cutaneous warts, human papillomavirus, immunotherapy, and tuberculin purified protein derivative. Original studies on treating cutaneous or anogenital warts with PPD were included. The results were 47 clinical trials and 4 case reports. Most of the research was done in countries with common Mycobacterium tuberculosis infection. The treatment showed good efficacy. Comparative studies showed that the treatment has similar efficacy with other immunotherapies. No significant side effects were reported, with evidence of the safety use on the pregnant population. Conclusion: Based on good efficacy and safety, PPD can be considered an alternative therapy, especially in countries where tuberculosis is frequent.

Assessing the Impact of the Zero Mother Mortality Preeclampsia Program on Maternal Mortality Rates at a Single Center in Bandung, West Java (2015-2022): A Retrospective Study.

BACKGROUND The Zero Mother Mortality Preeclampsia (ZOOM) program was adopted as an accelerated initiative to curb mortality related to hypertensive disorders in pregnancy, including preeclampsia. This single-center, retrospective study in Bandung, West Java, aims to evaluate the impact of the ZOOM program implemented from 2015 to 2022. MATERIAL AND METHODS We analyzed 19,176 childbirths and associated maternal deaths due to hypertension in pregnancy. Diagnoses were validated using blood pressure measures, lab tests including urine protein, liver function, blood profiles, platelets, X-ray, echocardiography, and COVID-19 testing. The case fatality rate (CFR) was assessed to evaluate the impact of the ZOOM program. RESULTS Hypertension in pregnancy was identified in 25.1% of cases, with 9.8% and 1.4% attributed to preeclampsia and eclampsia, respectively. Maternal deaths associated with hypertension accounted for 36.6%, with the majority linked to eclampsia. Heart failure (45.5%) and Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) syndrome (22%) were the most common complications. The CFR decreased from 61% in 2018 to 10% in 2022. The overall CFR from 2015 to 2022 was 1.3%, with the highest fatality rate observed in eclampsia cases (9.4%). However, a declining trend was seen since 2018, reaching a low of 0.2% in 2021. CONCLUSIONS The implementation of the ZOOM program, which includes preeclampsia re-education, early detection, prompt intervention, protocol adjustments, and a refined referral system, led to a marked reduction in maternal deaths from hypertensive pregnancy disorders.

Epigenetic Regulation Interplays with Endometriosis Pathogenesis in Low-Birth-Weight Patients via the Progesterone Receptor B-VEGF-DNMT1 Axis.

BACKGROUND: Low birth weight (LBW) is a risk factor associated with endometriosis. Our study aimed to analyze the risk of endometriosis in women with a LBW history and the relationships of progesterone receptor B (PR-B) gene promoter methylation, DNA methyltransferase-1 (DNMT1) expression, PR-B expression, and vascular endothelial growth factors (VEGF) with endometriosis. METHODS: This study was conducted in two stages, a retrospective case-control design and a cross-sectional design, with 52 cases of endometriosis and 30 controls, which were further subdivided into LBW and non-LBW groups, at Hasan Sadikin General Hospital and its hospital networks from October 2017 to August 2021. Menstrual blood was taken from subjects and analyzed using pyrosequencing techniques to assess DNA methylation, while q-RT PCR was used to assess gene expression. RESULTS: There were significant differences in PR-B methylation, DNMT1 expression, PR-B expression, and VEGF expression (p < 0.001) between the case and control groups. There was a significant negative correlation between PR-B methylation and PR-B expression (r = -0.558; p = 0.047). Based on a multiple logistic analysis, the most dominant factor affecting endometriosis incidence is PR-B (OR 10.40, 95% CI 3.24-33.4, R2 = 45.8). We found that patients with a low birth weight history had a 1.41-times-higher risk of developing endometriosis (95% CI 0.57-3.49, p = 0.113), although the relationship was not statistically significant. CONCLUSION: Endometriosis is associated with PR-B gene promoter hypermethylation, decreased PR-B expression, and increased DNMT1 and VEGF expression. The methylation of PR-B is the most dominant factor affecting endometriosis incidence.

Comparison of Extravillous Intermediate Trophoblast Invasion Depth and Distribution Pattern Between Placenta Accreta and Non-Accreta.

BACKGROUND Placenta accreta spectrum (PAS) is a complex obstetric complication that poses a major risk for life-threatening hemorrhage. The pathogenesis of PAS is known to be related to placentogenesis, trophoblastic cells invasion, and previous obstetrical procedures that cause uterine wall defects. However, the precise mechanism of this disease has not been fully explained. This study aimed to evaluate the differences in maximum depth of invasion and distribution pattern of implantation site intermediate trophoblasts between PAS and non-accreta cases. MATERIAL AND METHODS This was an observational, analytic, cross-sectional study that utilized paraffin block specimen of peripartum hysterectomy performed in Hasan Sadikin General Hospital Bandung from 2018 to 2020. Sixty-four samples were obtained, then classified as PAS and non-accreta (normal placenta). Implantation site-intermediate trophoblasts were identified using CD-146 staining. Maximum invasion depth of intermediate trophoblasts was measured in micrometers, while the distribution pattern was assessed and classified into 2 groups: confluent and scattered. RESULTS We found that the maximum invasion depth of the intermediate trophoblasts was significantly higher in the PAS group compared to that of the non-accreta group (2453.52±1172.122 µm vs 1613.59±822.588 µm, P=0.009). The confluent distribution pattern was significantly more common in the PAS group compared to that of the non-accreta group (87.2% vs 17.6%, P=0.0001). CONCLUSIONS The findings of our study suggested that implantation site intermediate trophoblasts play a role in the pathophysiology of placenta accreta. Further studies are needed to determine factors that affect trophoblast invasion leading to placenta accreta spectrum.

Successful treatment of anogenital warts with single dose Bacillus Calmette Guerin vaccine without prior sensitization in tuberculosis endemic country: Two case report.

Anogenital Warts (AGWs) are benign proliferations caused by Human Papillomavirus (HPV) infection on the genital or anal areas. Various therapeutic options are available for the treatment of AGWs but there is no best or ideal therapy, and the recurrence of AGWs is significantly high. A promising new therapy that is currently being evaluated is immunotherapy with the intralesional Bacillus Calmette-Guérin (BCG) vaccine. Two cases of a 23-year-old woman and a 41-year-old man were presented with manifestations of condyloma acuminata type AGWs. The patients were immunocompetent and received single dose intralesional BCG vaccine on the largest lesion. Clinical improvements of AGWs lesions were noted starting on the 14th day after receiving therapy by the disappearance of some lesions with no recurrence and side effects. Intralesional BCG vaccine activates the immune system, treats other AGWs lesions that do not receive an intralesional injection, and also prevents recurrence. Although the intralesional BCG vaccine is effective for treating AGWs, further evaluation is still needed for its recurrence.

Cervical pre-cancerous lesion detection: development of smartphone-based VIA application using artificial intelligence.

OBJECTIVE: Visual inspection of cervix after acetic acid application (VIA) has been considered an alternative to Pap smear in resource-limited settings, like Indonesia. However, VIA results mainly depend on examiner's experience and with the lack of comprehensive training of healthcare workers, VIA accuracy keeps declining. We aimed to develop an artificial intelligence (AI)-based Android application that can automatically determine VIA results in real time and may be further developed as a health care support system in cervical cancer screening. RESULT: A total of 199 women who underwent VIA test was studied. Images of cervix before and after VIA test were taken with smartphone, then evaluated and labelled by experienced oncologist as VIA positive or negative. Our AI model training pipeline consists of 3 steps: image pre-processing, feature extraction, and classifier development. Out of the 199 data, 134 were used as train-validation data and the remaining 65 data were used as test data. The trained AI model generated a sensitivity of 80%, specificity of 96.4%, accuracy of 93.8%, precision of 80%, and ROC/AUC of 0.85 (95% CI 0.66-1.0). The developed AI-based Android application may potentially aid cervical cancer screening, especially in low resource settings.

Comparison of the JCAHO Scoring System and the ESAS Scoring System in Determining the Palliative Care Needs of Gynecological Cancer Patients Treated at Hasan Sadikin Hospital.

OBJECTIVE: The purpose of this study was to analyze the relationship between quality of life with the JCAHO and the ESAS scoring system, and to compare the JCAHO and the ESAS scoring system in determining the palliative care needs of gynecological cancer patients treated at RSHS. METHOD: The subjects of this study were all gynecological cancer patients who were treated at RSHS in May-August 2020. This study was an analytic study with a cross sectional design. The data of this study were obtained from interviews, questionnaires and patient medical records, the study was analyzed bivariate using chi square with α = 0.05. RESULTS: The results showed that the quality of life of patients with gynecological cancer was associated with the JCAHO palliative score (p <0.05), the better the patient's quality of life, the better the JCAHO palliative score. The quality of life of gynecological cancer patients was related to ESAS (p <0.05), the better the patient's quality of life, the better the ESAS. There was difference between the JCAHO palliative score and the ESAS in determining the palliative care needs of gynecological cancer patients (p< 0.05). CONCLUSION: Quality of life has correlation with palliative scores, the lower the palliative score, the better the quality of life. This study showed significant difference between the JCAHO palliative score and the ESAS in determining the palliative care needs of gynecological cancer patients. The JCAHO palliative score measures objectively how the patient is on admission for treatment, this score not only measures the intensity of symptoms but measures the underlying disease, comorbid disease, functional status of the patient and other criteria for the patient.  ESAS assesses the intensity of symptoms, the assessment of palliative care needed can change rapidly if the intensity of symptoms in patients changes.

Success of Intralesional Purified Protein Derivative Immunotherapy in the Treatment of Anogenital Warts: A Case Report.

Anogenital warts (AGW) are among the most common sexually transmitted infections worldwide. The condition may be persistent, increase in size and number, and have a high recurrence rate. There are many therapeutic options of AGW, but none of them prevented recurrence, only yielded partial responses and have the propensity to cause scars. Immunotherapy by purified protein derivative (PPD) is one of the therapeutic options for AGW, which effectively reduces the number of lesions until complete clearance, with minimal side effects and less recurrence rate. This case report aims to demonstrate the effectiveness, safety, and low recurrence rate of intralesional PPD injection as an alternative therapy for AGW. We reported one case of AGW in an immunocompetent 30-year-old homosexual man who was given 3 doses of 0.2 mL PPD injected intralesionally. As a result, clinical improvement was observed starting from the 18th day, with some of the lesions decreasing in size, and on the 46th day, all of the lesions disappeared. There was no significant side effect. Within two years of follow-up, no recurrence was observed. Intralesional injection of PPD can stimulate the immune response against human papillomavirus (HPV) infection both on the injection site and distant from the injection site. Previous studies have shown promising results of intralesional PPD, with low recurrence in over six-month follow-up and no side effects. Intralesional injection of PPD can be considered as an alternative therapy due to its minimal side effects and its long-term low recurrence rate.

Potential of Mesenchymal Stem Cells and Their Secretomes in Decreasing Inflammation Markers in Polycystic Ovary Syndrome Treatment: A Systematic Review.

Background: Polycystic ovary syndrome (PCOS) is a chronic disorder and is one of the most common endocrine disorders in women of a reproductive age. The prevalence of PCOS is growing globally; 52% of women in Southeast Asia alone suffer from this disorder. This disorder is caused by chronic hyperandrogenism, which hinders folliculogenesis. There is also a close relationship between hyperandrogenism and hyperinsulinemia/insulin resistance (IR), and it is estimated that 40-80% of PCOS patients suffer from insulin resistance (IR). Mesenchymal stem cells (MSCs) and their secretomes have been shown to alleviate PCOS symptoms by decreasing IR and androgen secretion by reducing inflammation. This study aimed to systematically review the literature to study the reported potential of MSCs and their secretomes in decreasing inflammation markers in PCOS treatment. Methods: A systematic literature search was performed on EMBASE, PubMed (MEDLINE), and the Cochrane Library with the terms insulin-resistant PCOS, mesenchymal stem cells, and secretome or conditioned medium as the search keywords. A total of 317 articles were reviewed. Four articles were identified as relevant for this systematic review. Results: The results of this study supported the use of mesenchymal stem cells and their secretions in decreasing inflammatory markers in the treatment of polycystic ovary syndrome. Conclusions: This review provided evidence that treatment with mesenchymal stem cells and their secretomes has the potential to treat PCOS due to its ability to downregulate androgen levels and increase insulin sensitivity, which thereby lowers the level of proinflammatory factors.

A Case of Rapid Transformation from Hydatidiform Mole to Invasive Mole: The Importance of ß-hCG (Human Chorionic Gonadotropin) Serum Levels in Follow-Up Evaluation.

BACKGROUND Gestational trophoblastic disease (GTD) is a spectrum of disorders consisting of premalignant (ie, complete [CHM] and partial hydatidiform moles [PHM]) and malignant conditions (ie, invasive moles, choriocarcinoma, placental site trophoblastic tumors, and epithelioid trophoblastic tumor). If GTD persists after initial treatment and has persistent elevated beta human chorionic gonadotropin (ß-hCG), it is referred to as post-molar gestational trophoblastic neoplasia (pGTN). To date, there is no detailed information regarding how fast invasive moles can develop from CHM. However, the risk of developing any pGTN from CHM is rare within 1 month and is greatest in the first 12 months after evacuation, with most cases presenting within 6 months. CASE REPORT We present a case of a 46-year-old primigravida woman with rapid transformation of an invasive mole. In the beginning, the patient had a chief concern of a uterus size greater than the gestational dates. Laboratory evaluation showed high ß-hCG serum level (>300 000 mIU/mL), and ultrasonography evaluation revealed a hydatidiform mole. Suction evacuation and curettage procedures were then performed. Pathology evaluation afterwards revealed a complete hydatidiform mole without any sign of malignancy. Twenty-two days afterwards, the patient came to the emergency room with vaginal bleeding. ß-hCG serum level was high (53 969 mIU/mL), and ultrasonography examination showed the presence of fluid filling the uterine cavity. The patient was then diagnosed with GTN, and hysterectomy was chosen as the treatment of choice. After the surgery, her ß-hCG serum level gradually reverted back to normal. CONCLUSIONS Invasive moles can develop less than 1 month after suction evacuation and curettage procedure for CHM. Serial ß-hCG serum level evaluation according to the guideline should be performed to prevent late diagnosis, which could lead to the development of metastasis and worsen the prognosis.

A Rare Case of Early Transformation of Gestational Trophoblastic Neoplasia Following Molar Pregnancy.

BACKGROUND Gestational trophoblastic disease (GTD) encompasses a group of disorders that arise from abnormal growth of trophoblastic tissue. The spectrum of GTD includes 2 major groups: benign and malignant. The benign form is a hydatidiform mole, either complete or partial; the malignant forms, referred to as gestational trophoblastic neoplasia (GTN), consist of invasive moles, choriocarcinomas, placental site trophoblastic tumors, and epithelioid trophoblastic tumors. Most patients who undergo evacuation of a hydatidiform mole by curettage have a disease-free period before a new tumor develops that can be considered malignant. In rare cases, metastasis occurs rapidly and manifests coincidentally before the hydatidiform mole can be evacuated. CASE REPORT A 19-year-old woman in Bandung City, West Java, Indonesia, was diagnosed with a molar pregnancy with early evidence of a mass in her vagina that was suspicious for stage II GTN. The early emergence of a vaginal mass was a rare case of early transformation of a molar pregnancy into GTN. CONCLUSIONS Careful evaluation is warranted of patients with characteristics typical of an intrauterine molar pregnancy who have an early presentation of a vaginal mass because of the possibility that the diagnosis could be GTN.

Analysis of Curcumin as a Radiosensitizer in Cancer Therapy with Serum Survivin Examination: Randomised Control Trial.

OBJECTIVE: One of the important treatments for cervical cancer is radiation therapy. This study sought to determine the role of curcumin as a radio-sensitizing agent for use with radiation therapy for cervical cancer. To accomplish this, we assessed the levels of survivin, which is an anti-apoptotic protein that plays a role in cell division and apoptosis inhibition. METHOD: This study used a quasi-experimental design, including a pretest-posttest control group design approach. The study subjects included cervical carcinoma stage IIB-IIIB patients who were scheduled to undergo surgery at the Hasan Sadikin Hospital Bandung during the research period. The advanced cervical cancer patients were assigned to two groups: i) those who received curcumin + radiation therapy and ii) those who received placebo + radiation therapy. RESULTS: In the group treated with curcumin + radiation, 15 (75%) patients showed decreased survivin levels and 5 (25%) showed increased survivin levels. Whereas, in the placebo + radiation group, there were 8 (40%) patients who showed decreased survivin levels and 12 (60%) who showed increased survivin levels. CONCLUSION: In conclusion, curcumin is an effective, alternative radiosensitizer agent for application in cervical cancer treatment.
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Correlation of Serum Anti-Mullerian Hormone (AMH) Level on Ovarian Volume in Women with Endometrioma.

BACKGROUND: The correlation between endometrioma and serum Anti-mullerian hormone (AMH) level is a benchmark in determining the prognosis and management of endometrioma. Endometrioma causes a decrease in ovarian reserve due to tissue damage that affects the formation of serum AMH. Serum AMH levels in daily practice are useful as a tool to determine ovarian reserve, markers for diagnosis and prognosis in infertility and reproductive abnormalities. The purpose of this study was to determine the relationship of serum AMH level in women with endometrioma and their correlation to ovarian volume. METHODS: This research was an analytical observational study with a cross-sectional design in women of reproductive age who were diagnosed with endometrioma within the period of August 2019-March 2020 at Hasan Sadikin Hospital, Bandung. Forty-four women who met the inclusion and exclusion criteria were then divided into endometrioma (n=22) and control (n=22) groups. In both groups, transvaginal ultrasound examination was performed to measure the volume of the ovary, then a laboratory examination of serum AMH level was carried out. RESULTS: Serum AMH levels in the endometrioma group were significantly lower than those in the control group (P<0.001). Serum AMH level did not differ significantly based on laterality of the observation group (P=1.000). There was a negative correlation between serum AMH level and the volume of ovarian endometrioma, although not statistically significant (r=-0.332; P=0.066). CONCLUSION: There was a correlation between serum AMH level and endometrioma. Serum AMH levels were significantly lower in the endometrioma group but were not influenced by their laterality. We found a negative correlation between serum AMH level and ovarian volume containing endometrioma, but not statistically significant.

Chemokine Ligand 5 to Predict Optimal Cytoreduction in Ovarian Cancer.

PURPOSE: The ultimate goal of cytoreduction surgery is the complete removal of all visible tumors (complete cytoreductive surgery) or tumor residues <1 cm (optimal cytoreduction surgery). Following cytoreduction surgery in ovarian cancer, tumor residue is one of the most important prognostic factors. Oncologists strive to be able to predict the outcome of cytoreduction surgery during the presurgical period. The purpose of this study was to assess CCL5 as a modality for determining whether a patient could perform optimal cytoreduction surgery or not. MATERIALS AND METHODS: This was an observational, analytic, and cross-sectional study of patients with ovarian cancer who underwent surgery at the Dr. Hasan Sadikin Bandung from 2019 to 2020. All of the patients had stage I-IV disease based on the International Federation of Gynecology and Obstetrics (FIGO) score. RESULTS: In total, 72 patients were enrolled in this study, 31 of whom underwent suboptimal cytoreduction surgery and 41 underwent optimal cytoreduction surgery. The mean serum CCL5 level at suboptimal cytoreduction was 70,920.87 ± 36,362.966, while that at optimal cytoreduction was 43,244.95 ± 21,983.887. CCL5, as a predictor of suboptimal cytoreduction surgery, had a sensitivity of 61.3%, a specificity of 68.3%, and an accuracy of 65.7% (p = 0.012). CONCLUSION: Preoperative CCL5 serum levels can predict suboptimal cytoreduction surgery outcomes in patients with ovarian cancer.

Efficacy of Oral Vitamin A in Reducing ß-hCG Levels in Low-Risk Gestational Trophoblastic Neoplasia Patients.

OBJECTIVE: Low-risk gestational trophoblastic neoplasia (GTN) is generally treated with single agent chemotherapy and methotrexate (MTX) as a first-line therapy. Vitamin A helps to increase trophoblast cell regression, as well as to decrease ß-hCG levels. Vitamin A also increases the effectiveness of MTX by inducing more malignant cell death than MTX alone. Therefore, the aim of the current study was to analyze the changes in ß-hCG levels in low-risk GTN patients following vitamin A administration. METHODS: This study was a randomized clinical trial, which examined initial serum vitamin A and ß-hCG levels in GTN patients before and after three cycles of MTX therapy. Patients were given vitamin A supplementation of 6,000 IU (1.8 mg RAEs) per day, and the changes in serum ß-hCG were observed after three cycles. Patients were grouped by ß-hCG levels (decreased or stagnant). RESULTS: A total of 32 low-risks GTN patients were divided into the intervention group (16 patients who received vitamin A supplementation) and the control group (16 patients who did not receive vitamin A supplementation). In the intervention group, the average initial ß-hCG level was 170,949.3 ± 354,452.1 mIU/mL, and the average ß-hCG post-cycle level was 1,611.9 ± 3,652.5 mIU/mL. In the control group, the average initial ß-hCG level was 178,834.1 ± 2913844.6 mIU/mL, and the average ß-hCG post-cycle level was 25,388.5 ± 58,437.7 mIU/mL. CONCLUSION: In patients with low-risk GTN who underwent MTX chemotherapy, the levels of ß-hCG and the incidence of chemo resistance in the intervention group were lower than those in the control group. Older age may also influence the incidence of chemo resistance in GTN patients. Oral administration of 6,000 IU vitamin A could help to reduce ß-hCG levels in low-risk GTN patients who receive MTX chemotherapy.
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Pulsatility Index and Hypoxia Inducible Factor-1α Expression Predict the Clinical Response after External Radiation in Patients with Stage IIB to IVA Cervical Cancer.

Objective: To evaluate the ability of pulsatility index (PI), resistance index (RI), and hypoxia inducible factor-1α (HIF-1α) expression in predicting the clinical response after radiation in patients with cervical cancer. Methods: A prospective cohort was carried on in Department of Obstetric and Gynecology Dr. Hasan Sadikin Hospital/ Faculty of Medicine, Padjadjaran University, during the period of July 2017 to March 2018 which include 51 samples with stage IIB to IVA cervical cancer. Tumor perfusion and oxygenation were evaluated using color Doppler ultrasound indices (pulsatility index and resistance index) and the expression of hypoxia inducible factor-1α (HIF-1α). The clinical response was assessed 2 months after external radiation. Result: Among 51 patients, 31 patients demonstrated good response and 20 patients demonstrated poor response to radiation. The mean value of PI was significantly lower in patients who demonstrated good response as compared to patients with poor response (0.84±0.916 vs. 1.70±1.260, p = 0.004). The mean value of RI did not differ significantly (0.29±0.112 vs. to 0.36±0.189 p =0.173). HIF-1α expression was significantly lower in patients who demonstrated good response as compared to patients with poor response (1.83±1.529 vs. 6.55±2.625, p = 0.0001). In multivariate model, PI and HIF-1α expression both predicted the clinical response after radiation. Conclusion: PI and HIF-1α expression predict the clinical response after radiation in patients with cervical cancer.