Determinants for male involvement in family planning and contraception in Nakawa Division, Kampala, Uganda; An urban slum qualitative study.

Current evidence shows that male involvement in family planning (FP) is crucial to women's contraceptive use decisions. This study explored the reasons for male involvement in FP and contraception in slum areas in Nakawa Division, Kampala, Uganda. A qualitative study was conducted among sexually active males in a slum area in Nakawa Division, Kampala. A purposive sampling technique was utilised to recruit 40 men for a Focus Group Discussion (FGDs), and 2 key informants (KI) for critical perspective interviews. A semi-structured FGDs and interview guides were used to collect the data. The FGDs were conducted in both English and the local language, Luganda. All interviews were recorded and transcribed verbatim. Transcripts for both FGDs and KI interviews were imported into the NVivo Qualitative Data Analysis Software version 10 application, and thematic data analysis was conducted. The findings show that males' involvement in FP and its decisions were minimal. The findings also show that several factors emerged as contributing to male's participation in FP and utilisation of contraceptives. Inadequate understanding of FP and contraceptives, lack of clarity on males' role in FP, unfriendly healthcare environment and community members' perceptions of male involvement in FP were reported as reasons contributing to male participation in FP and contraction. There is limited involvement of males in FP. There is a need for renewed efforts that will positively alter the factors that impact male involvement favourably. Promotion and education about FP for males will significantly address issues of limited understanding and clarity of males' role in FP services.

High-Grade Endometrial Cancer: Molecular Subtypes, Current Challenges, and Treatment Options.

Although many recent advancements have been made in women's health, perhaps one of the most neglected areas of research is the diagnosis and treatment of high-grade endometrial cancer (EnCa). The molecular classification of EnCa in concert with histology was a major step forward. The integration of profiling for mismatch repair deficiency and Human Epidermal Growth Factor 2 (HER2) overexpression, can further inform treatment options, especially for drug resistant recurrent disease. Recent early phase trials suggest that regardless of subtype, combination therapy with agents that have distinct mechanisms of action is a fruitful approach to the treatment of high-grade EnCa. Unfortunately, although the importance of diagnosis and treatment of high-grade EnCa is well recognized, it is understudied compared to other gynecologic and breast cancers. There remains a tremendous need to couple molecular profiling and biomarker development with promising treatment options to inform new treatment strategies with higher efficacy and safety for all who suffer from high-grade recurrent EnCa.

Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors.

PURPOSE: MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi. PATIENTS AND METHODS: We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts for: pancreatic, gynecologic (GYN), non-small cell lung cancer (NSCLC), and other cancers harboring KRAS/NRAS mutations. Paired pretreatment and day 15 tumor biopsies and serial cell-free (cf)DNA were analyzed. RESULTS: A total of 91 patients initiated treatment, with 38 in dose escalation. Fifty-eight percent had ≥3 prior therapies. A total of 15 patients (17%) had colorectal cancer, 19 (11%) pancreatic, 15 (17%) NSCLC, and 32 (35%) GYN cancers. The recommended phase II dose (RP2D) was established as trametinib 2 mg daily days 1 to 14 and navitoclax 250 mg daily days 1 to 28 of each cycle. Most common adverse events included diarrhea, thrombocytopenia, increased AST/ALT, and acneiform rash. At RP2D, 8 of 49 (16%) evaluable patients achieved partial response (PR). Disease-specific differences in efficacy were noted. In patients with GYN at the RP2D, 7 of 21 (33%) achieved a PR and median duration of response 8.2 months. No PRs occurred in patients with colorectal cancer, NSCLC, or pancreatic cancer. MAPK pathway inhibition was observed in on-treatment tumor biopsies. Reductions in KRAS/NRAS mutation levels in cfDNA correlated with clinical benefit. CONCLUSIONS: Navitoclax in combination with trametinib was tolerable. Durable clinical responses were observed in patients with RAS-mutant GYN cancers, warranting further evaluation in this population.

Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma.

BACKGROUND: Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3's role in promoting USC pathology is lacking. METHODS: We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3's impact on cell function. RESULTS: TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids. CONCLUSION: These findings suggest inhibiting Gal3 may benefit USC patients.

Differential Clubbing and a Triad of Patent Ductus Arteriosus, Ventricular Septal Defect and Supravalvular Ring Mitral Stenosis: A Case Report.

It is not uncommon for congenital heart defects to occur in clusters. Those involving a right to left heart shunt commonly cause cyanosis and finger clubbing. Differential clubbing involving only the lower limb digits is a strong pointer to the presence of patent ductus arteriosus with reversal of shunt. We report a case of 25-year-old man with effort intolerance and differential clubbing. He was found to have the uncommon triad of patent ductus arteriosus, ventricular septal defect and supravalvular ring mitral stenosis. The presence of differential clubbing on a background of patent ductus arteriosus usually indicates a reversal of shunt and negates surgical intervention. This general rule may however not apply with co-existing mitral stenosis as the elevated pulmonary pressure may be predominantly post-capillary. The finding of mitral stenosis in a patient with patent ductus arteriosus and differential limb clubbing may signify a good prognostic surgical outcome.

Il n'est pas rare que des malformations cardiaques congénitales surviennent en clusters. Celles impliquant un shunt cardiaque droitegauche provoquent souvent une cyanose et un hippocratisme digital. L'hippocratisme digital différentiel touchant uniquement les orteils des membres inférieurs est un indicateur fort de la présence d'un canal artériel persistant avec inversion du shunt. Nous rapportons le cas d'un homme de 25 ans présentant une intolérance à l'effort et un hippocratisme digital différentiel. Il a été diagnostiqué avec la triade peu commune de canal artériel persistant, de communication interventriculaire et de sténose mitrale à anneau supravalvulaire. La présence d'un hippocratisme digital différentiel sur un fond de canal artériel persistant indique généralement une inversion du shunt et exclut une intervention chirurgicale. Cependant, cette règle générale peut ne pas s'appliquer en présence d'une sténose mitrale concomitante, car la pression pulmonaire élevée peut être principalement post-capillaire. La découverte d'une sténose mitrale chez un patient atteint de canal artériel persistant et d'un hippocratisme digital différentiel peut indiquer un bon pronostic pour l'intervention chirurgicale.

Structural basis for antibody recognition of the proximal MUC16 ectodomain.

BACKGROUND: Mucin 16 (MUC16) overexpression is linked with cancer progression, metastasis, and therapy resistance in high grade serous ovarian cancer and other malignancies. The cleavage of MUC16 forms independent bimodular fragments, the shed tandem repeat sequence which circulates as a protein bearing the ovarian cancer biomarker (CA125) and a proximal membrane-bound component which is critical in MUC16 oncogenic behavior. A humanized, high affinity antibody targeting the proximal ectodomain represents a potential therapeutic agent against MUC16 with lower antigenic potential and restricted human tissue expression. RESULTS: Here, we demonstrate the potential therapeutic versatility of the humanized antibody as a monoclonal antibody, antibody drug conjugate, and chimeric antigen receptor. We report the crystal structures of 4H11-scFv, derived from an antibody specifically targeting the MUC16 C-terminal region, alone and in complex with a 26-amino acid MUC16 segment resolved at 2.36 Å and 2.47 Å resolution, respectively. The scFv forms a robust interaction with an epitope consisting of two consecutive ß-turns and a ß-hairpin stabilized by 2 hydrogen bonds. The VH-VL interface within the 4H11-scFv is stabilized through an intricate network of 11 hydrogen bonds and a cation-π interaction. CONCLUSIONS: Together, our studies offer insight into antibody-MUC16 ectodomain interaction and advance our ability to design agents with potentially improved therapeutic properties over anti-CA125 moiety antibodies.

Phase IIa Study of PLX2853 in Gynecologic Cancers With Known ARID1A Mutation and Phase Ib/IIa Study of PLX2853/Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer.

PURPOSE: The Bromodomain and Extra-Terminal (BET) domain proteins facilitate the development of many human cancers via epigenetic regulation. BET inhibitors may be effective in reversing platinum resistance in ovarian cancer (OC) and may generate synthetic lethality with ARID1A loss. PLX2853 is an orally active, small-molecule inhibitor of BET bromodomain-mediated interactions that exhibits low nanomolar potency in blocking all four BET family members. METHODS: We conducted a multicenter and open-label study with two parallel arms: a phase IIa study of PLX2853 monotherapy in patients with advanced gynecologic malignancies with an ARID1A mutation and a phase Ib/IIa combination study of PLX2853 plus carboplatin in women with platinum-resistant OC. The primary objectives were safety and tolerability for phase Ib and efficacy for both phase IIa portions. Thirty-four of 37 enrolled patients completed at least one post-baseline response assessment. RESULTS: Of the 14 evaluable patients on the monotherapy arm, 1 (7.1%) achieved a best overall response of partial response (PR), 5 (35.7%) had stable disease (SD), and 8 (57.1%) had progressive disease (PD). Of the 20 evaluable patients on the combination arm, 1 (5.0%) had PR, 9 (45.0%) had SD, and 10 (50%) had PD. CONCLUSION: This study confirmed the safety profile of PLX2853 and demonstrated the feasibility of combination with carboplatin. Although these results did not meet the prespecified response criteria, evidence of clinical activity highlights the rationale for further exploration of BET inhibitors in patients with ARID1A-mutated gynecologic malignancies, possibly in combination with agents targeting potential feedback mechanisms such as the PI3K pathway.

Alzheimer's disease: The role of T lymphocytes in neuroinflammation and neurodegeneration.

Alzheimer's disease, the leading cause of progressive cognitive decline globally, has been reported to be enhanced by neuroinflammation. Brain-resident innate immune cells and adaptive immune cells work together to produce neuroinflammation. Studies over the past decade have established the neuroimmune axis present in Alzheimer's disease; the crosstalk between adaptive and innate immune cells within and outside the brain is crucial to the onset and progression of Alzheimer's disease. Although the role of the adaptive immune system in Alzheimer's disease is not fully understood, it has been hypothesized that the brain's immune homeostasis is significantly disrupted, which greatly contributes to neuroinflammation. Brain-infiltrating T cells possess proinflammatory phenotypes and activities that directly contribute to neuroinflammation. The pro-inflammatory activities of the adaptive immune system in Alzheimer's disease are characterized by the upregulation of effector T cell activities and the downregulation of regulatory T cell activities in the brain, blood, and cerebrospinal fluid. In this review, we discuss the major impact of T lymphocytes on the pathogenesis and progression of Alzheimer's disease. Understanding the role and mechanism of action of T cells in Alzheimer's disease would significantly contribute to the identification of novel biomarkers for diagnosing and monitoring the progression of the disease. This knowledge could also be crucial to the development of immunotherapies for Alzheimer's disease.

Reasons and prevention strategies of unintended pregnancy in Addis Ababa, Ethiopia: a phenomenological qualitative study.

OBJECTIVES: To explore the reasons for unintended pregnancy and effective prevention measures from the perspectives of women and healthcare providers in Addis Ababa, Ethiopia. DESIGN: Phenomenological qualitative study. SETTING AND PARTICIPANTS: This study was conducted at three public health facilities found in Addis Ababa, Ethiopia. Women with unintended pregnancies and healthcare providers currently working in maternal health services were purposively recruited for in-depth interviews. Twenty in-depth interviews were conducted until data saturation was achieved. Data were analysed using thematic analysis. RESULTS: Seven themes emerged from the transcribed interview data. These include: Personal characteristics (negligence; lower pregnancy expectation), family influence (fear of family), sociocultural and economic influence (stigma and discrimination), healthcare provider influence (disrespectful and abusive approach; disregard for women's contraceptive choice), preconception thoughts and behaviours (unprotected early sexual practice; myths and misunderstanding), lack of access to quality family planning services (lack of trained contraceptive counsellor, inappropriate contraceptive use), and preventive strategies for unintended pregnancy (comprehensive sexual education; sexual and reproductive health and rights service integration) CONCLUSIONS: This study identified multilevel reasons for unintended pregnancy from the perspective of the participants. Participants shared their views on preventive measures for unintended pregnancy, including comprehensive sexual education, service integration and male-inclusive contraceptive counselling. This study highlights the need to improve sexual and reproductive health services by shedding light on the viewpoints and experiences of women and healthcare providers.

Association between unintended pregnancy and maternal antenatal care services use in Ethiopia: analysis of Ethiopian demographic and health survey 2016.

Introduction: Unintended pregnancy disproportionately affects women in low and middle-income countries including Ethiopia. Previous studies identified the magnitude and negative health outcomes of unintended pregnancy. However, studies that examined the relationship between antenatal care (ANC) utilization and unintended pregnancy are scarce. Objective: This study aimed to examine the relationship between unintended pregnancy and ANC utilization in Ethiopia. Methods: This is a cross-sectional study conducted using the fourth and most recent Ethiopian Demographic Health Survey (EDHS) data. The study comprised a weighted sample of 7,271 women with last alive birth and responded to questions on unintended pregnancy and ANC use. The association between unintended pregnancy and ANC uptake was determined using multilevel logistic regression models adjusted for possible confounders. Finally p < 5% was considered significant. Results: Unintended pregnancy accounted for nearly a quarter of all pregnancies (26.5%). After adjusting for confounders, a 33% (AOR: 0.67; 95% CI, 0.57-0.79) lower odds of at least one ANC uptake and a 17% (AOR: 0.83; 95% CI, 0.70-0.99) lower odds of early ANC booking were found among women who had unintended pregnancy compared to women with intended pregnancy. However, this study founds no association (AOR: 0.88; 95% CI, 0.74, 1.04) between unintended pregnancy and four or more ANC visits. Conclusion: Our study found that having unintended pregnancy was associated with a 17 and 33% reduction in early initiation and use of ANC services, respectively. Policies and programs designed to intervene against barriers to early initiation and use of ANC should consider unintended pregnancy.

Protein-protein interaction and interference of carcinogenesis by supramolecular modifications.

Protein-protein interactions (PPIs) are essential in normal biological processes, but they can become disrupted or imbalanced in cancer. Various technological advancements have led to an increase in the number of PPI inhibitors, which target hubs in cancer cell's protein networks. However, it remains difficult to develop PPI inhibitors with desired potency and specificity. Supramolecular chemistry has only lately become recognized as a promising method to modify protein activities. In this review, we highlight recent advances in the use of supramolecular modification approaches in cancer therapy. We make special note of efforts to apply supramolecular modifications, such as molecular tweezers, to targeting the nuclear export signal (NES), which can be used to attenuate signaling processes in carcinogenesis. Finally, we discuss the strengths and weaknesses of using supramolecular approaches to targeting PPIs.

Identification of HER2 inhibitors from curcumin derivatives using combination of in silico screening and molecular dynamics simulation.

Breast cancer remains a major world health challenge in women. Some Breast cancers are human epidermal growth factor receptor 2 (HER2) positive. Since this protein promotes the growth of cancer cells, it remains a therapeutic target for novel drugs. This study uses in silico model to predict HER2 inhibitors from curcumin derivatives via QSAR, e-pharmacophore, ADMET as well as structure-based virtual screening using Schrodinger suite. The molecular dynamics simulation of lead compounds, reference ligand and co-crystalized ligand was performed using GROMACS. At the end, eight active curcumin derivatives were predicted as inhibitors of HER2 with high binding affinity and better interaction compared with the reference drug (Neratinib) but lower binding affinity compared with the co-crystalized ligand (TAK-285). After prediction of the bioactivity of the molecules using AutoQSAR, the hit compounds showed appreciable inhibitory pIC50 compared with the reference and co-crystalized ligands against HER2. The pharmacokinetics profile predicted the eight hit compounds as drug-like and drug candidates. The MD simulation predicted the stability of the two top-scored compounds (10763284 and 78321412) in complex with HER2 for the final 80 ns of the trajectory period after initial equilibration with higher H-bond interactions in the protein-reference drug complex compared to the hit compounds-HER2 complexes. This study revealed that curcumin derivatives especially (1E,6E)-1,8-bis(4-hydroxy-3-methoxyphenyl)octa-1,6-diene-3,5-dione and (1E,6E)-4-ethyl-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione were identified to demonstrate inhibitory activity against HER2 which is comparable to neratinib. Conclusively, the lead compounds require further in vitro and in vivo experimental validation for the discovery of new HER2 antagonists for breast cancer management.Communicated by Ramaswamy H. Sarma.

Clinical Characteristics, Management, and Six-Month Outcomes after Discharge of Patients Admitted for Acute Heart Failure in Ibadan, Nigeria.

BACKGROUND: The burden of acute heart failure (AHF) is on the increase globally however, there are few studies on AHF in Nigeria and among black populations. OBJECTIVE: This study described the clinical profile, conventional management and six-months outcome after discharge of patients admitted for acute heart failure at the University College Hospital, Ibadan, Nigeria. METHODS: The study was a prospective study of 160 consecutive AHF patients. Socio-demographic details, clinical history, basic laboratory parameters electrocardiographic and echocardiographic parameters were assessed. They were followed-up for six-months after discharge to ascertain death or readmission. RESULTS: The mean ± standard deviation (SD) age of all the patients was 58.0 ±15.1 years. Those aged 60 years and above constituted about half of the participants. Males comprised 59.3% and hypertension was the most common risk factor (77.5%). One hundred and thirty-four subjects (83.8%) were in New York Heart Association functional classes III or IV. The most common AHF type was heart failure with reduced ejection fraction and mostly presented de novo. The mean duration of admission was 11 days while intrahospital mortality and mortality at 6 months after discharge were 6.3% and 25.6% respectively. CONCLUSION: This study provided a real-world data of AHF at UCH, Ibadan, Nigeria. It showed AHF was predominantly associated with hypertension. There was high mortality among these AHF subjects. There is a need for more strategy in our environment for preventing AHF and its adverse outcomes.

CONTEXTE: Le fardeau de l'insuffisance cardiaque aiguë (ICA) est en augmentation dans le monde entier ; cependant, il existe peu d'études sur l'ICA au Nigeria et parmi les populations noires. OBJECTIF: Cette étude décrit le profil clinique, la prise en charge conventionnelle et le résultat six mois après la sortie des patients admis pour une insuffisance cardiaque aiguë à l'University College Hospital, Ibadan, Nigeria. MÉTHODES: L'étude était une étude prospective de 160 patients consécutifs souffrant d'insuffisance cardiaque aiguë. Les détails sociodémographiques, l'histoire clinique, les paramètres de laboratoire de base, les paramètres électrocardiographiques et échocardiographiques ont été évalués. Ils ont été suivis pendant six mois après leur sortie de l'hôpital pour vérifier le décès ou la réadmission. RÉSULTATS: L'âge moyen ± écart-type (ET) de tous les patients était de 58,0 ±15,1 ans. Les personnes âgées de 60 ans et plus constituaient environ la moitié des participants. Les hommes représentaient 59,3 % et l'hypertension était le facteur de risque le plus fréquent (77,5 %). Cent trente-quatre sujets (83,8 %) appartenaient aux classes fonctionnelles III ou IV de la New York Heart Association. Le type d'AHF le plus fréquent était l'insuffisance cardiaque avec fraction d'éjection réduite et se présentait le plus souvent de novo. La durée moyenne d'admission était de 11 jours tandis que la mortalité intrahospitalière et la mortalité à 6 mois après la sortie étaient respectivement de 6,3% et 25,6%. CONCLUSION: Cette étude a fourni des données réelles de l'AHF à l'UCH, Ibadan, Nigeria. Elle a montré que l'AHF était principalement associée à l'hypertension. Il y avait une mortalité élevée parmi ces sujets AHF. Il y a un besoin de plus de stratégie dans notre environnement pour prévenir l'AHF et ses résultats défavorables. Mots-clés: Insuffisance cardiaque. Insuffisance cardiaque aiguë, Nigeria, Hypertension, Maladie cardiovasculaire.

Regulation of effector and memory CD8 + T cell differentiation: a focus on orphan nuclear receptor NR4A family, transcription factor, and metabolism.

CD8 + T cells undergo rapid expansion followed by contraction and the development of memory cells after their receptors are activated. The development of immunological memory following acute infection is a complex phenomenon that involves several molecular, transcriptional, and metabolic mechanisms. As memory cells confer long-term protection and respond to secondary stimulation with strong effector function, understanding the mechanisms that influence their development is of great importance. Orphan nuclear receptors, NR4As, are immediate early genes that function as transcription factors and bind with the NBRE region of chromatin. Interestingly, the NBRE region of activated CD8 + T cells is highly accessible at the same time the expression of NR4As is induced. This suggests a potential role of NR4As in the early events post T cell activation that determines cell fate decisions. In this review, we will discuss the influence of NR4As on the differentiation of CD8 + T cells during the immune response to acute infection and the development of immunological memory. We will also discuss the signals, transcription factors, and metabolic mechanisms that control cell fate decisions. HIGHLIGHTS: Memory CD8 + T cells are an essential subset that mediates long-term protection after pathogen encounters. Some specific environmental cues, transcriptional factors, and metabolic pathways regulate the differentiation of CD8 + T cells and the development of memory cells. Orphan nuclear receptor NR4As are early genes that act as transcription factors and are highly expressed post-T cell receptor activation. NR4As influence the effector function and differentiation of CD8 + T cells and also control the development of immunological memory following acute infection.

Mass Spectrometric ITEM-ONE and ITEM-TWO Analyses Confirm and Refine an Assembled Epitope of an Anti-Pertuzumab Affimer.

Intact Transition Epitope Mapping-One-step Non-covalent force Exploitation (ITEM-ONE) analysis reveals an assembled epitope on the surface of Pertuzumab, which is recognized by the anti-Pertuzumab affimer 00557_709097. It encompasses amino acid residues NSGGSIYNQRFKGR, which are part of CDR2, as well as residues FTLSVDR, which are located on the variable region of Pertuzumab's heavy chain and together form a surface area of 1381.46 Å2. Despite not being part of Pertuzumab's CDR2, the partial sequence FTLSVDR marks a unique proteotypic Pertuzumab peptide. Binding between intact Pertuzumab and the anti-Pertuzumab affimer was further investigated using the Intact Transition Epitope Mapping-Thermodynamic Weak-force Order (ITEM-TWO) approach. Quantitative analysis of the complex dissociation reaction in the gas phase afforded a quasi-equilibrium constant (KD m0g#) of 3.07 × 10-12. The experimentally determined apparent enthalpy (ΔHm0g#) and apparent free energy (ΔGm0g#) of the complex dissociation reaction indicate that the opposite reaction-complex formation-is spontaneous at room temperature. Due to strong binding to Pertuzumab and because of recognizing Pertuzumab's unique partial amino acid sequences, the anti-Pertuzumab affimer 00557_709097 is considered excellently suitable for implementation in Pertuzumab quantitation assays as well as for the accurate therapeutic drug monitoring of Pertuzumab in biological fluids.

Intraperitoneal Therapy for Ovarian Cancer - Some Answers, More Questions, and Missed Opportunities.

Intraperitoneal (i.p.) therapy set a new treatment standard for patients with advanced-stage ovarian cancer in 2006 based on data showing improved overall survival in the trial by Armstrong et al.1 This trial showed a statistically significant and clinically meaningful improvement in median overall survival of almost 16 months in favor of patients treated with i.p. chemotherapy compared with an intravenous approach. Since then, several clinical trials have aimed to better understand what population of patients are most likely to benefit from this therapy. Will patients with earlier-stage disease or suboptimal cytoreduction after surgery benefit? Does tumor histology matter?