Peritoneal metastases from rare ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

Objectives: There are limited treatment options and no consensus on the management of advanced rare ovarian malignancies. Rare ovarian malignancies can present with peritoneal metastases (PM), featuring a similar presentation to more common ovarian subtypes. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an effective treatment for PM of non-gynecologic origin and, recently, epithelial ovarian cancer. We evaluated the feasibility of CRS/HIPEC in the management of PM from rare ovarian malignancies and report postoperative outcomes on these patients. Methods: A retrospective review of a single center, prospective database (1994-2021) was performed to identify patients with rare ovarian malignancies treated with CRS/HIPEC. Clavien-Dindo 90-day morbidity/mortality and Kaplan-Meier overall (OS) and progression-free survival (PFS) were analyzed. Results: Of 44 patients identified, 28 underwent CRS/HIPEC. Six were aborted due to extensive disease. Histologic subtypes included: clear cell (5/28, 17.9 %), endometrioid (5/28, 17.9 %), granulosa cell (3/28, 10.7 %), low-grade serous (6/28, 21.4 %), mesonephric (1/28, 3.6 %), mucinous (6/28, 21.4 %), and small cell (2/28, 7.1 %) carcinomas. Eight (28.6 %) patients had primary and 20 (71.4 %) had recurrent disease. Median peritoneal cancer index (PCI) was 21 (IQR: 6-29). Complete cytoreduction (<2.5 mm residual disease) was achieved in 27/28 (96.4 %). Grade III/IV complications occurred in 9/28 (32.1 %) with one (3.6 %) mortality. After a median follow-up of 65.8 months, 20 patients were alive. Five-year OS and PFS were 68.5 and 52.6 %, respectively. Conclusions: In patients with PM from rare ovarian malignancies, CRS/HIPEC is feasible and has an acceptable safety profile. Longer follow-up and multicenter trials are needed.

Collaborative expertise of gynecological and surgical oncologists in managing advanced epithelial ovarian cancer.

BACKGROUND: Most patients with epithelial ovarian cancer (EOC) present with significant peritoneal spread. We assessed collaborative efforts of surgical and gynecological oncologists with expertise in cytoreductive surgery (CRS) in the management of advanced EOC. METHODS: Using a prospective single-center database (2014-2022), we described the operative and oncologic outcomes of stage IIIC-IVA primary and recurrent EOC perioperatively managed jointly by gynecological and surgical oncologists both specializing in CRS and presented components of this collaboration. RESULTS: Of 199 identified patients, 132 (66 %) had primary and 53 (27 %) had recurrent EOC. Due to inoperable disease, 14 (7 %) cases were aborted and excluded from analysis. Median peritoneal cancer index (PCI) in primary and recurrent patients was 21 (IQR: 11-28) and 21 (IQR: 6-31). Upper abdominal surgery was required in 95 % (n = 125) of primary and 89 % (n = 47) of recurrent patients. Bowel resections were performed in 83 % (n = 110) and 72 % (n = 38), respectively. Complete cytoreduction (CC-0/1) with no disease or residual lesions <2.5 mm was achieved in 95 % (n = 125) of primary and 91 % (n = 48) of recurrent patients. Ninety-day Clavien-Dindo grade III-IV morbidity was 12 % (n = 16) and 21 % (n = 11), respectively. Median follow-up was 44 (95%CI: 33-55) months. Median overall survival in primary and recurrent EOC was 68 (95%CI: 45-91) and 50 (95%CI: 16-84) months. Median progression-free survival was 26 (95%CI: 22-30) and 14 (95%CI: 7-21) months, respectively. CONCLUSIONS: Perioperative collaboration between surgical and gynecological oncologists specializing in CRS allows safe performance of complete cytoreduction in the majority of patients with primary and recurrent EOC, despite high tumor burden.

Sufficient Regional Lymph Node Examination for Staging Adenocarcinoma of the Appendix.

BACKGROUND: The presence of lymph node (LN) metastasis is a known negative prognostic factor in appendix cancer (AC) patients. However, currently the minimum number of LNs required to adequately determine LN negativity is extrapolated from colorectal studies and data specific to AC is lacking. We aimed to define the lowest number of LNs required to adequately stage AC and assess its impact on oncologic outcomes. METHODS: Patients with stage II-III AC from the National Cancer Database (NCDB 2004-2019) undergoing surgical resection with complete information about LN examination were included. Multivariable logistic regression assessed the odds of LN positive (LNP) disease for different numbers of LNs examined. Multivariable Cox regressions were performed by LN status subgroups, adjusted by prognostic factors, including grade, histologic subtype, surgical approach, and documented adjuvant systemic chemotherapy. RESULTS: Overall, 3,602 patients were included, from which 1,026 (28.5%) were LNP. Harvesting ten LNs was the minimum number required without decreased odds of LNP compared with the reference category (≥ 20 LNs). Total LNs examined were < 10 in 466 (12.9%) patients. Median follow-up from diagnosis was 75.4 months. Failing to evaluate at least ten LNs was an independent negative prognostic factor for overall survival (adjusted hazard ratio 1.39, p < 0.01). CONCLUSIONS: In appendix adenocarcinoma, examining a minimum of ten LNs was necessary to minimize the risk of missing LNP disease and was associated with improved overall survival rates. To mitigate the risk of misclassification, an adequate number of regional LNs must be assessed to determine LN status.

Factors associated with mental health in Peruvian medical students during the COVID-19 pandemic: a multicentre quantitative study.

OBJECTIVE: To assess the mental health status and associated factors of Peruvian medical students during the COVID-19 pandemic. METHODS: Descriptive, multicentre, correlational study that used the "Patient Health Questionnaire-9 (PHQ-9)", the "Generalized Anxiety Disorder-7 (GAD-7)" and the "Impact of Event Scale-Revised (IES-R)" questionnaires to evaluate mental health problems. RESULTS: A total of 1,238 students from 8 Peruvian medical schools participated in the study. Of these, 68.5% were women, and the mean age was 21.4 years. Depressive symptoms were found in 74% of the participants, anxiety symptoms in 57% and distress symptoms in 65%. The variables associated with the development of symptoms of moderate-severe depression, anxiety and distress were: not having family economic stability, being in the first years of medical training, being female, and fearing that their medical training would be delayed and impaired. CONCLUSIONS: In a sample of medical students surveyed during the COVID-19 pandemic, mental health problems were common. The factors associated with mental health reported in this study could be useful in identifying vulnerable medical students who require timely psychosocial support and/or psychiatric care.

Patterns of Recurrence in Appendix Cancer After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: It is thought that low-grade (LG) appendiceal cancer (AC) demonstrates predominantly intraperitoneal recurrence (IPR) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), whereas high-grade (HG) tumors progress both intra- and extraperitoneally (EPR). However, evidence supporting this conception is lacking; therefore, we assessed recurrence in various AC histologies. METHODS: A retrospective, cohort study was conducted by using a single-center database (1998-2022). Recurrence patterns (IPR, EPR, combined) were identified for LG, HG, high-grade with signet ring cells (SRC), and goblet cell carcinoma (GCC). RESULTS: We included 432 complete (CC-0/1) CRS/HIPECs: 200 LG, 114 HG, 72 SRC, and 46 GCC. Median follow-up was 78 (95% confidence interval [CI] 70-86) months. Overall, 34% (n = 148) of patients recurred. IPR was the most common (LG 16%, HG 27%, SRC 36%, GCC 26%) with median time to recurrence (MTR) of 21 (IQR: 12-40) months. EPR (liver, lung, pleura, lymph nodes, or bones) occurred in LG 3%, HG 9%, SRC 22%, and GCC 7%. MTR was 11 (IQR: 4-16) months. Combined pattern occurred in LG 0%, HG 8%, SRC 7%, and GCC 0%. MTR was 13 (IQR: 7-18) months. Iterative surgery was performed in 53% IPR, 18% EPR, and 51% combined. Median post-recurrence survival was longer after IPR compared with EPR and combined recurrence: 36 (95% CI 25-47) versus 13 (95% CI 7-19) and 18 (95% CI 6-30) months (p < 0.01). CONCLUSIONS: After complete CRS/HIPEC, IPR was the predominant pattern in all AC histologies and occurred later. Post-recurrence survival after IPR was longer. Knowing AC recurrence patterns can help to understand its biology and plan follow-up and post-relapse management.

Degradable Hydrogel for Sustained Localized Delivery of Anti-Tumor Drugs.

Disadvantages of systemically administered immunomodulatory anti-tumor therapies include poor efficacy and high toxicity. Direct intratumoral injection of a drug is often associated with rapid efflux from the site of administration, thus reducing local exposure and therapeutic efficacy, while potentially increasing systemic adverse events. To address this, a sustained release prodrug technology was developed using a transient conjugation (TransConTM) technology to provide long-term high local drug exposure after injection in the tumor while minimizing systemic exposure. TransCon technology for systemic delivery is clinically validated, with multiple compounds in late-stage clinical development and approval of a once-weekly growth hormone for pediatric growth hormone deficiency. As a further application of this technology, this report describes the design, preparation, and functional characterization of hydrogel microspheres as insoluble, yet degradable carrier system. Microspheres were obtained after reaction of PEG-based polyamine dendrimers and bifunctional crosslinkers. Resiquimod, a TLR7/8 agonist, and axitinib, a vascular endothelial growth factor tyrosine kinase inhibitor, were chosen as anti-cancer drugs. The drugs were covalently attached to the carrier by linkers, which released the drugs under physiological conditions. Essentially all resiquimod or axitinib was released over weeks before physical degradation of the hydrogel microsphere was observed. In summary, TransCon Hydrogel technology allows localized sustained-release drug delivery for cancer therapy enabling high local drug concentrations while at the same time ensuring low systemic drug exposure over weeks with a single injection, which may improve the therapeutic index and improve efficacy, while minimizing systemic adverse events. A hydrogel prodrug of resiquimod, TransCon TLR7/8 agonist, is currently being investigated in clinical trials of patients with solid tumors (NCT04799054).

Achieving Intraperitoneal Disease Control Using Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Two Cases of Metastatic Breast Cancer.

Peritoneal metastases from breast cancer (PMBC) tend to occur late in the disease course and are challenging to manage. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) provide peritoneal disease control in other malignancies and may achieve similar results in PMBC. We assessed intraperitoneal disease control and outcomes in two PMBC patients after CRS/HIPEC. Patient 1, diagnosed at age 64, had hormone-positive/human epidermal growth factor receptor 2 (HER2)-negative lobular carcinoma treated with mastectomy. Prior to salvage CRS/HIPEC at age 72, five cycles of intraperitoneal chemotherapy via an indwelling catheter failed to control recurrent peritoneal disease. Patient 2, diagnosed at age 52, had hormone-positive/HER2-negative ductal-lobular carcinoma and received lumpectomy, hormonal therapy, and target therapy. Prior to salvage CRS/HIPEC at age 59, she had recurring ascites that was resistant to hormonal therapy and required multiple paracenteses. Both underwent complete CRS/HIPEC with melphalan. The only major complication was anemia, which required a transfusion in both patients. They were discharged on postoperative days 8 and 13, respectively. Patient 1 had peritoneal recurrence 26 months post-CRS/HIPEC and died of disease at 49 months. Patient 2 never had peritoneal recurrence and died of extraperitoneal progression at 38 months. In conclusion, CRS/HIPEC is safe and can provide intraperitoneal disease and symptom control in select patients with PMBC. Thus, CRS/HIPEC can be offered to these rare patients who have failed standard treatments.

Outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal dissemination from ovarian carcinosarcoma.

BACKGROUND: Ovarian carcinosarcoma (OCS) is an uncommon and aggressive malignancy, with poor response to current treatment approaches and no clear guidelines. Our aim is to evaluate the outcomes of an OCS cohort after cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: A descriptive cohort study was performed. Patients who underwent CRS/HIPEC for peritoneal dissemination from tubo-ovarian malignancies (1999-2021) were retrospectively reviewed. Patients with confirmed histopathologic diagnosis of FIGO stage III/IV OCS were included. Overall (OS) and progression-free survival (PFS) were determined with the Kaplan-Meier method. RESULTS: Of 267 patients with tubo-ovarian malignancies reviewed, 7.5% (20/267) had OCS. Of these, 16 underwent CRS/HIPEC, including 9 for a new diagnosis and 7 for disease recurrence. Median age at surgery was 66.5 (IQR: 54.5-74.5) years. Nine (56.2%) patients were FIGO stage IV. Median peritoneal cancer index was 22 (IQR: 14-28). Complete cytoreduction was achieved in 15/16 (93.7%) cases. HIPEC agents included carboplatin (n = 7), cisplatin+doxorubicin (n = 4), and melphalan (n = 5). Major complications occurred in 4/16 (25%), with no 90-day mortality. Median follow-up was 41.8 months. Median PFS was 11.7 (95%CI: 10.5-17.1) months. Malignant bowel obstruction occurred in 3/16 (18.7%). Median OS from CRS/HIPEC was 21.3 (95%CI: 16.3-31.6) months, not reached for newly diagnosed vs 19.7 months for recurrent patients (p = 0.23). CONCLUSIONS: CRS/HIPEC showed promising survival and abdominal disease control with low rates of malignant obstruction in patients with advanced stage OCS. Collaborative studies with larger cohorts and longer follow-up may further elucidate the role of CRS/HIPEC in OCS.

Long-chain polyunsaturated lipids associated with responsiveness to anti-PD-1 therapy are colocalized with immune infiltrates in the tumor microenvironment.

The programmed cell death protein-1 (PD-1) is highly expressed on the surface of antigen-specific exhausted T cells and, upon interaction with its ligand PD-L1, can result in inhibition of the immune response. Anti-PD-1 treatment has been shown to extend survival and result in durable responses in several cancers, yet only a subset of patients benefit from this therapy. Despite the implication of metabolic alteration following cancer immunotherapy, mechanistic associations between antitumor responses and metabolic changes remain unclear. Here, we used desorption electrospray ionization mass spectrometry imaging to examine the lipid profiles of tumor tissue from three syngeneic murine models with varying treatment sensitivity at the baseline and at three time points post-anti-PD-1 therapy. These imaging experiments revealed specific alterations in the lipid profiles associated with the degree of response to treatment and allowed us to identify a significant increase of long-chain polyunsaturated lipids within responsive tumors following anti-PD-1 therapy. Immunofluorescence imaging of tumor tissues also demonstrated that the altered lipid profile associated with treatment response is localized to dense regions of tumor immune infiltrates. Overall, these results indicate that effective anti-PD-1 therapy modulates lipid metabolism in tumor immune infiltrates, and we thereby propose that further investigation of the related immune-metabolic pathways may be useful for better understanding success and failure of anti-PD-1 therapy.

Factors associated with suicidal ideation among medical students during the initial phase of the COVID-19 pandemic in Peru: A multicenter study.

We aimed to describe the prevalence and factors associated with suicidal ideation in a sample of 1238 medical students from different medical schools in Peru based on question 9 of the Patient Health Questionnaire (PHQ-9). Our results revealed that 17.9% of the participants had suicidal ideation. Furthermore, using logistic regression, we found that not practicing any religion, the presence of clinically significant depression, and the presence of clinically significant anxiety were statistically related to the presence of suicidal ideation. Our results indicate that suicidal ideation was highly prevalent in the sample of medical students studied.

Association between Factor-V Leiden and occurrence of acute myocardial infarction using a large NIS database.

Factor V Leiden is an inheritable pro-thrombotic genetic condition caused by a point mutation at the 506th codon, resulting in activated protein C resistance. APC resistance has been shown to contribute to the development of venous thrombosis. However, the role of FVL in AMI has yet to be well defined in the current literature. To assess whether a mutation carrier is more apt to develop an AMI, we conducted a retrospective observational analysis of two populations aged 18-40 and 18 through end of life. We used ICD-10 codes to search the NIS, an electronic nationwide patient database, to establish our populations and obtain our data. The ICD-10 codes were specific for activated protein C resistance and acute myocardial infarction. Preliminary data indicated that FVL was related to AMI; however, this finding became insignificant in both populations when stratified for age. We concluded there was no association between Factor V Leiden and acute myocardial infarction across both examined populations. Future investigations into this field of research are warranted as there remains a need for more consensus among the scientific community. BACKGROUND: Medical literature regarding the correlation between Factor V Leiden (FVL) and acute myocardial infarctions (AMI) is controversial. We aim to investigate the association between FVL and AMI. MATERIALS AND METHODS: Using the Nationwide Inpatient Sample database, we evaluated any association between Factor V Leiden and acute myocardial infarction in 2016 using ICD-10 codes. RESULTS: Univariate analysis (18-40) showed an increase of AMI in patients with FVL 0.6% vs. 0.4%. However, after adjustment for age and comorbid conditions in multivariate analysis, FVL was not significantly associated with acute myocardial infarction (OR 1.44 (95% CI 0.913-2.273, p-value 0.117)). Univariate analysis (all patients over 18 years old) found that 2.9% of patients with FVL experienced AMI vs. 4.4% without the mutation. Multivariate analysis of the entire population ultimately showed no correlation between FVL and AMI. CONCLUSION: In a population over 18, Factor V Leiden did not correlate with an increased risk of acute myocardial infarction in our studied population.

Thyroid hormones: Metabolism and transportation in the fetoplacental unit.

The thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), are of vital importance for fetal development. The concentration of THs in fetal circulation varies throughout gestation and differs from the concentration in the maternal serum, indicating the presence of maternal-fetal thyroid homeostasis regulatory mechanisms in the placenta. The passage of THs from maternal circulation to fetal circulation is modulated by plasma membrane transporters, enzymes, and carrier proteins. Monocarboxylate transporter 8, iodothyronine deiodinases (DIO2 and DIO3), and transthyretin are especially involved in this maternal-fetal thyroid modulation, shown by a greater expression in the placenta. THs also play a role in placental development and as expected, abnormal variations in TH levels are associated with pregnancy complications and can result in damage to the fetus. Although new evidence regarding TH regulation during pregnancy and its effects in the mother, placenta, and fetus has been published, many aspects of these interactions are still poorly understood. The objective of this review is to provide an evidence-based update, drawn from current data, on the metabolism and transport of THs in the placenta and their vital role in the maternal-fetal relationship.

Intratumoral delivery of TransCon™ TLR7/8 Agonist promotes sustained anti-tumor activity and local immune cell activation while minimizing systemic cytokine induction.

BACKGROUND: Intratumoral (IT) delivery of toll-like receptor (TLR) agonists has shown encouraging anti-tumor benefit in preclinical and early clinical studies. However, IT delivery of TLR agonists may lead to rapid effusion from the tumor microenvironment (TME), potentially limiting the duration of local inflammation and increasing the risk of systemic adverse events. METHODS: To address these limitations, TransCon™ TLR7/8 Agonist-an investigational sustained-release prodrug of resiquimod that uses a TransCon linker and hydrogel technology to achieve sustained and predictable IT release of resiquimod-was developed. TransCon TLR7/8 Agonist was characterized for resiquimod release in vitro and in vivo, in mice and rats, and was assessed for anti-tumor efficacy and pharmacodynamic activity in mice. RESULTS: Following a single IT dose, TransCon TLR7/8 Agonist mediated potent tumor growth inhibition which was associated with sustained resiquimod release over several weeks with minimal induction of systemic cytokines. TransCon TLR7/8 Agonist monotherapy promoted activation of antigen-presenting cells in the TME and tumor-draining lymph nodes, with evidence of activation and expansion of CD8+ T cells in the tumor-draining lymph node and TME. Combination of TransCon TLR7/8 Agonist with systemic immunotherapy further promoted anti-tumor activity in TransCon TLR7/8 Agonist-treated tumors. In a bilateral tumor setting, combination of TransCon TLR7/8 Agonist with systemic IL-2 potentiated tumor growth inhibition in both injected and non-injected tumors and conferred protection against tumor rechallenge following complete regressions. CONCLUSIONS: Our findings show that a single dose of TransCon TLR7/8 Agonist can mediate sustained local release of resiquimod in the TME and promote potent anti-tumor effects as monotherapy and in combination with systemic immunotherapy, supporting TransCon TLR7/8 Agonist as a novel intratumoral TLR agonist for cancer therapy. A clinical trial to evaluate the safety and efficacy of TransCon TLR7/8 Agonist, as monotherapy and in combination with pembrolizumab, in cancer patients is currently ongoing (transcendIT-101; NCT04799054).

TransCon IL-2 ß/γ: a novel long-acting prodrug with sustained release of an IL-2Rß/γ-selective IL-2 variant with improved pharmacokinetics and potent activation of cytotoxic immune cells for the treatment of cancer.

BACKGROUND: Recombinant interleukin-2 (IL-2, aldesleukin) is an approved cancer immunotherapy but causes severe toxicities including cytokine storm and vascular leak syndrome (VLS). IL-2 promotes antitumor function of IL-2Rß/γ+ natural killer (NK) cells and CD8+, CD4+ and gamma delta (γδ) T cells. However, IL-2 also potently activates immunosuppressive IL-2Rα+ regulatory T cells (Tregs) and IL-2Rα+ eosinophils and endothelial cells, which may promote VLS. Aldesleukin is rapidly cleared requiring frequent dosing, resulting in high Cmax likely potentiating toxicity. Thus, IL-2 cancer immunotherapy has two critical drawbacks: potent activation of undesired IL-2Rα+ cells and suboptimal pharmacokinetics with high Cmax and short half-life. METHODS: TransCon IL-2 ß/γ was designed to optimally address these drawbacks. To abolish IL-2Rα binding yet retain strong IL-2Rß/γ activity, IL-2 ß/γ was created by permanently attaching a small methoxy polyethylene glycol (mPEG) moiety in the IL-2Rα binding site. To improve pharmacokinetics, IL-2 ß/γ was transiently attached to a 40 kDa mPEG carrier via a TransCon (transient conjugation) linker creating a prodrug, TransCon IL-2 ß/γ, with sustained release of IL-2 ß/γ. IL-2 ß/γ was characterized in binding and primary cell assays while TransCon IL-2 ß/γ was studied in tumor-bearing mice and cynomolgus monkeys. RESULTS: IL-2 ß/γ demonstrated selective and potent human IL-2Rß/γ binding and activation without IL-2Rα interactions. TransCon IL-2 ß/γ showed slow-release pharmacokinetics with a low Cmax and a long (>30 hours) effective half-life for IL-2 ß/γ in monkeys. In mouse tumor models, TransCon IL-2 ß/γ promoted CD8+ T cell and NK cell activation and antitumor activity. In monkeys, TransCon IL-2 ß/γ induced robust activation and expansion of CD8+ T cells, NK cells and γδ T cells, relative to CD4+ T cells, Tregs and eosinophils, with no evidence of cytokine storm or VLS. Similarly, IL-2 ß/γ enhanced proliferation and cytotoxicity of primary human CD8+ T cells, NK cells and γδ T cells. SUMMARY: TransCon IL-2 ß/γ is a novel long-acting prodrug with sustained release of an IL-2Rß/γ-selective IL-2. It has remarkable and durable pharmacodynamic effects in monkeys and potential for improved clinical efficacy and tolerability compared with aldesleukin. TransCon IL-2 ß/γ is currently being evaluated in a Phase 1/2 clinical trial (NCT05081609).

Advanced Abdominal Ectopic Pregnancy with Subsequent Fetal and Placental Extraction: A Case Report.

Abdominal ectopic pregnancy (AEP) occurs within the peritoneal cavity, outside the genital organs (uterus, tubes, ovaries). It is an unusual condition with an incidence that varies from 1:10,000 to 1:30,000 of all pregnancies worldwide. A 38-year-old primigravid patient was diagnosed in the second trimester with AEP. Pregnancy reached 35.6 gestational weeks, and the patient underwent surgery via laparotomy for extraction of the live fetus. Complete removal of the placenta was performed without maternal or fetal complications. AEP is an important cause of maternal and fetal death; the mortality rate in pregnant women with AEP is approximately 1-18%. Surgical intervention to deliver a baby in cases of AEP requires a multidisciplinary team, especially in countries with limited therapeutic options.

Management practices for placenta accreta spectrum patients: a Latin American hospital survey.

INTRODUCTION: Placenta accreta spectrum (PAS) causes severe morbidity and can result in maternal death. It must be managed in specialized centers with interdisciplinary groups, but few publications have described the usual management within a specific geographic region. We intend to describe the usual approach for PAS in reference centers in Latin America. METHODOLOGY: This was an observational, multicenter, cross-sectional study conducted in Latin American PAS reference centers. A standardized survey was implemented and applied to obstetric service coordinators and leaders of interdisciplinary groups with experience in PAS between September and November 2020. RESULTS: One hundred fifty-four hospitals were included. Most of them (64.3%) handle approximately one case of PAS every two months, and almost all centers (89.6%) believe that their performance could be improved. CONCLUSIONS: Most of the reference centers for PAS in Latin America attend to a small number of cases each year, and almost all of these hospitals identify opportunities to improve the management or approach for PAS in women.

Tratamiento de la eclampsia y miastenia gravis: reporte de un caso y revisión de la literatura / Eclampsia treatment and myasthenia gravis: case report and review of literature

OBJETIVO: Reportar el caso de una gestante con miastenia grave (MG) más preeclampsia-eclampsia y crisis miasténica en el puerperio mediato, y realizar una revisión de la literatura sobre el manejo farmacológico. MÉTODO: Se presenta el caso de una mujer de 26 años con MG, primigesta de 36 semanas de gestación, quien cursó con eclampsia y recibió fenitoína por 24 horas. Tuvo parto espontáneo sin complicaciones y crisis miasténica al día 11 del puerperio asociada a infección de vías urinarias y sepsis. Se realiza revisión de la literatura en PubMed, Cochrane, Embase, LILACS y Scopus, empleando los términos "Hypertension, Pregnancy-Induced", "Preeclampsia" y "Eclampsia", combinados con "Myasthenia Gravis", durante el periodo de publicación de 1960 a junio 2020, en inglés y español. RESULTADOS: Se encontraron 12 reportes de caso, dos con eclampsia y MG; el caso aquí reportado es el número 13. Ocho pacientes no recibieron medicamentos profilácticos de eclampsia y tres de ellas convulsionaron. En las que se usó sulfato de magnesio, todas cursaron con crisis miasténica. CONCLUSIONES: La evidencia actual en cuanto a la profilaxis y el tratamiento de la eclampsia y la MG corresponde a reportes de casos. El uso de sulfato de magnesio está contraindicado en pacientes con MG, por lo que se han utilizado fenitoína y levetiracetam.

OBJECTIVE: To report a case of pregnant women with myasthenia gravis (MG), plus preeclampsia-eclampsia and myasthenic crisis in the mediate puerperium; to conduct a literature review regarding its pharmacological management. METHOD: 26-year-old primigravida with 36 weeks of gestation and previous history of MG, who developed eclampsia and was treated with phenytoin for 24 hours, with later spontaneous delivery without any complications nor new seizures; and myasthenic crisis on day 11 of the puerperium associated with urinary tract infection and sepsis. A literature review was conducted in PubMed, Cochrane, Embase, LILACS and Scopus, using the controlled vocabulary "Hypertension, Pregnancy-Induced", "Preeclampsia" and "Eclampsia", combined with "Myasthenia Gravis", between 1960 and June 2020, in English and Spanish. RESULTS: 12 case reports were found, two of these with eclampsia and MG, the case reported here was number 13. In eight cases patients did not receive any prophylactic drugs for eclampsia and three of them had convulsions. In the cases where magnesium sulfate was used, all developed myasthenic crisis. CONCLUSIONS: The current evidence regarding prophylactic management and treatment corresponds to case reports. The use of magnesium sulfate is contraindicated in patients with MG, therefore phenytoin and levetiracetam have been used.

Aciclovir endovenoso como tratamiento en la parálisis facial periférica e idiopática en un recién nacido. Reporte de caso

Introducción: la parálisis facial neonatal debida a la parálisis de Bell es rara. El mecanismo de parto traumático representa una etiología más común. Caso clínico: neonato, previamente sano, con parto espontáneo no instrumentalizado y sin complicaciones obstétricas, que cursó con parálisis facial derecha aguda. La imagen cerebral fue normal y los hallazgos clínicos compatibles con parálisis de Bell, con buena respuesta al manejo antirretroviral y fisioterapia. Discusión: la mayoría de infantes con parálisis de Bell mejora con o sin tratamiento y sin secuelas graves. No hay evidencia concluyente en la población pediátrica sobre el beneficio de usar esteroides, solos o con antirretrovirales. Actualmente, tampoco existe un consenso sobre la seguridad de usar esteroides posnatales tardíos, que se deben reservar para neonatos sin otra opción. El aciclovir a dosis de 60 mg/Kg/día es seguro en neonatos. Conclusiones: la parálisis de Bell neonatal puede presentar una respuesta favorable a la terapia antirretroviral y fisioterapia, prescindiendo del uso de esteroides.

SUMMARY Introduction: Neonatal facial palsy due to Bell's palsy is rare. A traumatic delivery mechanism represents a common etiology. Clinical case: Neonate, without previous illnesses, born by spontaneous non-instrumentalized delivery and without any obstetric complications; who presented acute right facial palsy, with normal brain imaging and clinical findings compatible with Bell's palsy, who had a good response to antiretroviral management and physical therapy. Discussion: Most infants with Bell's palsy improve with or without treatment, with no serious sequelae. In pediatric population, evidence on benefits of steroids use, alone or with antiretrovirals, has not been conclusive. There is not a current consensus on the safety of late postnatal steroid use, and they should be reserved for neonates who have no other treatment choice. Acyclovir use at 60/mg/Kg/day it's safe in neonates. Conclusions: Neonatal Bell's palsy may present a favorable response to antiretroviral therapy and an adherent physical rehabilitation program, irrespective of steroids use.