Carboplatin in Patients With Metastatic Castration-Resistant Prostate Cancer Harboring Somatic or Germline Homologous Recombination Repair Gene Mutations: Phase II Single-Arm Trial.

BACKGROUND: Approximately 20%-25% of patients with metastatic castration-resistant prostate cancer (mCRPC) harbor a deleterious germline or somatic mutation in the homologous recombination repair (HRR) pathway genes, which is involved in the repair of double-stranded DNA damage. Half of these mutations are germline, while the remaining are exclusively somatic. While polyadenosine 5'diphosphoribose [poly (ADP-ribose)] polymerase inhibitors, such as olaparib and rucaparib, are effective in this subgroup, their widespread use is limited due to the associated high cost, especially in resource-constrained settings. Notably, platinum agents like carboplatin have exquisite sensitivity to cells with defective DNA repair machinery. Carboplatin, a conventional, inexpensive chemotherapeutic agent, offers a potential alternative treatment in such patients. Several retrospective small case series support this hypothesis. However, there are no prospective clinical trials of carboplatin in patients with mCRPC with HRR mutations. OBJECTIVE: The primary objective is to assess the objective response rate of 3 weekly carboplatin treatments in patients with mCRPC harboring deleterious mutations in the HRR pathway genes and previously treated with a taxane or a novel antiandrogen agent. The secondary objectives include progression-free survival, health-related quality of life, and safety profile of carboplatin. METHODS: Patients diagnosed with mCRPC harboring HRR pathway mutations previously treated with docetaxel or novel antiandrogen agents (abiraterone, enzalutamide, apalutamide, or darolutamide) or both will be eligible. Genes involved directly or indirectly in the HRR pathway will be tested. In this single-arm phase II study, we will screen approximately 200 patients to enroll 49 patients, and carboplatin (dosing at the area under curve=5) will be administered every 3 weeks until progression or intolerable side effects. The primary end point will be assessed as the proportion of patients with a reduction of serum prostate-specific antigen by more than 50% from enrollment. Secondary outcomes include progression-free survival-soft-tissue disease progression (by response evaluation criteria in solid tumors, version 1.1, and bone lesion progression using Prostate Cancer Clinical Trials Working Group 3 criteria), health-related quality of life during carboplatin treatment using the Functional Assessment of Cancer Therapy-Prostate questionnaire and the European Organisation for Research and Treatment of Cancer questionnaire and safety profile of carboplatin (National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0). RESULTS: The trial started enrollment in September 2023. This trial is ongoing, and 12 patients have been recruited to date. All 49 participants will be enrolled according to plan. CONCLUSIONS: This prospective phase II trial represents a critical step toward addressing the therapeutic gap in patients with mCRPC harboring HRR pathway mutations, particularly in demographic regions with limited access to poly (ADP-ribose) polymerase inhibitors. Outcomes from this study will inform clinical practice and guide future phase III randomized trials, ultimately improving patient outcomes globally. TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/2023/04/051507; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Njc0NjU=&Enc=&userName=. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54086.

Menace of hepatitis E in pregnancy: unleashing the threat of fulminant liver failure.

This case report presents a primigravida in her 20s with a history of seizure disorder and chronic cholecystitis, who presented at 30 weeks and 6 days of gestation with upper abdominal pain, fever and vomiting. Initially diagnosed with acute calculous cholecystitis, the patient's condition rapidly deteriorated, resulting in fetal demise and the development of severe complications. Subsequent investigations revealed an enlarged fatty liver and signs of acute liver failure. The diagnosis of acute fatty liver of pregnancy was initially considered but later ruled out, and the patient was diagnosed with hepatitis E based on positive anti-hepatitis E virus IgM antibodies. Prompt termination of pregnancy was performed, followed by intensive care management. After a prolonged hospital stay, the patient recovered and was discharged in stable condition. This case emphasises the importance of considering hepatitis E as a potential cause of acute liver failure in pregnant women and the need for early recognition and multidisciplinary management to achieve favourable outcomes.

Comprehensive germline profiling of patients with breast cancer: initial experience from a Familial Cancer Clinic.

Introduction: Breast cancer is the most common cancer among Indian females. There is limited data on germline profiling of breast cancer patients from India. Objective: The objective of the current study was to analyse the frequency and spectrum of germline variant profiles and clinicopathological characteristics of breast cancer patients referred to our Familial Cancer Clinic (FCC). Materials and methods: It is a single-centre audit of patients with a confirmed diagnosis of breast carcinoma referred to our FCC from January 2017 to 2020. All patients underwent pretest counselling. Genetic testing was done by multigene panel testing by next-generation sequencing along with reflex multiplication ligation-dependent probe amplification for BRCA1 and 2. The variants were classified based on American College of Medical Genetics guidelines. Demographic and clinicopathological details were extracted from the case record files. Results: One hundred and fifty-five patients were referred to the FCC and underwent pretest counselling. A total of 99 (63.9%) patients underwent genetic testing. Among them, 62 patients (62/99 = 62.6%) had a germline variant. A pathogenic/likely pathogenic (P/LP) germline variant was identified in 41 (41.4%) of the patients who underwent testing. Additional variants of unknown significance (VUS) were identified in seven patients who also carried a P/LP variant. VUS alone was detected in 21 patients (21/99 = 21.2%). Among the P/LP pathogenic variants (PV), BRCA 1 PV were seen in 27 patients (65.8%), BRCA 2 variants in 7 patients (17.1%), ATM variants in 3 patients (7.3%) and RAD51, TP53, CHEK2 and HMMR in 1 patient each. Variants were significantly more common in patients with a family history (FH) of malignancy than those without FH (58.5% versus 29.5%; p = 0.013). Age and triple-negative histology were not found to be significantly associated with the occurrence of P/LP PVs. Conclusion: We report a 41% P/LP variant rate in our selected cohort of breast cancer patients, with variants in BRCA constituting 83% and non-BRCA gene variants constituting 17%.

Fetomaternal outcomes in pregnant women with congenital heart disease: a comparative analysis from an apex institute.

OBJECTIVE: With advancements in cardiac surgical interventions during infancy and childhood, the incidence of maternal congenital heart disease (CHD) is increasing. This retrospective study compared fetal and cardiac outcomes in women with and without CHD, along with a sub-analysis between cyanotic versus non-cyanotic defects and operated versus non-operated cases. METHODS: A 10-year data were retrospectively collected from pregnant women with CHD and a 1:1 ratio of pregnant women without any heart disease. Adverse fetal and cardiac outcomes were noted in both groups. Statistical significance was set at P<0.05. RESULTS: A total of 86 pregnant women with CHD were studied, with atrial septal defects (29.06%) being the most common. Out of 86 participants, 27 (31.39%) had cyanotic CHD. Around 55% of cases were already operated on for their cardiac defects. Among cardiovascular complications, 5.8% suffered from heart failure, 7.0% had pulmonary arterial hypertension, 8.1% presented in New York Heart Association functional class IV, 9.3% had a need for intensive care unit admission, and one experienced maternal mortality. Adverse fetal outcomes, including operative vaginal delivery, mean duration of hospital stay, fetal growth restriction, preterm birth (<37 weeks), low birth weight (<2,500 g), 5-minute APGAR score <7, and neonatal intensive care unit admissions, were significantly higher in women with CHD than in women without heart disease. CONCLUSION: Women with CHD have a higher risk of adverse fetal and cardiac outcomes. The outcome can be improved with proper pre-conceptional optimization of the cardiac condition, good antenatal care, and multidisciplinary team management.

SMART-ESAS: Smartphone Monitoring and Assessment in Real Time of Edmonton Symptom Assessment System Scores for Patients With Cancer.

PURPOSE: Serial patient-reported outcome (PRO) measurements in clinical practice are associated with a better quality of life and survival. Recording electronic PROs using smartphones is an efficient way to implement this. We aimed to assess the feasibility of the electronically filled Edmonton Symptom Assessment System (e-ESAS) scale in the lower-middle-income country (LMIC) setting. METHODS: Baseline clinical features and conventional paper-based ESAS (p-ESAS) were collected in newly diagnosed patients with solid organ tumors. Text message link was sent to these patients for filling e-ESAS. ESAS was categorized into physical, psychological, and total symptom domains. Scores were divided into none to mild (0-3) and moderate to severe (4-10). Intraclass correlation coefficients (ICCs) were used to determine the correlation between p-ESAS and e-ESAS. Multivariable logistic regression was used to identify independent factors affecting symptom burden. RESULTS: Of 1,160 participants who filled out p-ESAS, 595 completed both e-ESAS and p-ESAS questionnaires and were included in the final analysis. Moderate to severe physical, psychological, and total symptom scores were seen in 39.8%, 40%, and 39% of participants. Tiredness and anxiety were the most common physical and psychological symptoms, respectively. ICCs between the p-ESAS and e-ESAS varied between 0.75 and 0.9. Total symptom scores were independently predicted by metastatic disease (odds ratio [OR], 1.83; 95% CI, 1.26 to 2.67; P = .001) and a higher level of education (OR, 0.42; 95% CI, 0.25 to 0.72; P = .001). CONCLUSION: Paper-based and electronically filled ESASs have good intraobserver reliability across individual symptoms and domain scores in a representative cohort at a tertiary care institute in the LMIC. This may help us incorporate e-ESAS in routine clinical care in the real-world setting with financial, infrastructural, and manpower limitations.

Minimally invasive autopsy in the evaluation of fetal malformations and stillbirths: A feasibility study.

BACKGROUND: Minimally invasive autopsy (MIA) using post-mortem magnetic resonance imaging with ancillary investigations is reported as accurate as conventional autopsy. This study assesses MIA's feasibility and accuracy compared to conventional autopsy. METHOD: MIA and/or conventional autopsy were performed on malformed fetuses (14-20 weeks gestation) and stillbirths (>20 weeks gestation), with/without malformation. Concordance in diagnostic accuracy (95% confidence interval [CI]) and agreement (Kappa coefficient [k]) were assessed in malformed cases where both MIA and autopsy were conducted. RESULTS: We enrolled 200 cases, including 100 malformed fetuses (<20 weeks) and 100 stillbirths (with/without malformations). Concordance of 97.3% was observed between MIA and autopsy in 156 malformed cases. The overall diagnostic accuracy of MIA was 96.04%. CONCLUSION: While conventional autopsy remains the gold standard, MIA is feasible in tertiary care settings. It can be considered a potential alternative for post-mortem assessment, particularly in settings with limited facility of conventional autopsy and parental refusal.

Introducing Birth Companion in Labour: A Quality Improvement Initiative.

Background: Birth companion (BC) has been globally recognised as an essential component of childbirth care. As our institution did not allow BC in labour, this study was planned as a quality improvement (QI) project to introduce the concept. We aimed to achieve birth companionship from existing 0 to 100% over a period of six months. Intervention: QI team was constituted, and an initial brainstorming session conducted. A fishbone diagram was drawn to analyse issues that need addressal before implementation of the initiative. The framework was defined, and team members assigned their roles and responsibilities. A series of five successive Plan-Do-Study-Act (PDSA) cycles were carried out over a period of six months, which included introduction of the concept, dissemination of information, infrastructural changes in labour room and introducing column for documentation in birth register. To achieve sustainability, comprehensive group counselling sessions were started for women during antenatal period, and sensitisation classes were regularly conducted for newly inducted trainees and faculty. Result: Birth companionship was achieved in 98% of cases. Conclusion: The QI tools helped in preparation and planning of changes by breaking down a large problem into smaller sections and covering all aspects of challenges in a systematic manner using team-based approach. National directives and recommendations, sensitisation of leadership and training of stakeholders were found to be important facilitators. Robust systems of monitoring and successive PDSA cycles were needed for continuous improvement and sustainability of the idea.

Comparison of Accuracy of Freestyle Libre Pro and Medtronic iPro2 Continuous Glucose Monitoring Systems in Pregnancy.

There are limited data on head-to-head performance of Freestyle Libre Pro (FSL-Pro) and blinded Medtronic iPro2 continuous glucose monitoring system in pregnancy. In this prospective observational study, women with hyperglycemia in pregnancy (n = 42) underwent simultaneous FSL-Pro and Medtronic iPro2 sensor insertion and self-monitoring of blood glucose using Contour Plus meter (reference). The overall mean absolute relative difference (MARD) for iPro2 and FSL-Pro systems were 8.0% ± 9.2% and 19.0% ± 12.7%, respectively. At hypoglycemic range, both sensors performed less accurately (MARD: 18.0% and 16.8%, respectively), whereas iPro2 showed higher accuracy at euglycemic (8.2% and 19.3%, respectively) and hyperglycemic (6.8% and 18.0%, respectively) ranges. On Bland-Altman analysis, iPro2 and FSL-Pro underestimated glucose by 0.01 and 1.09 mmol/L, respectively. The ISO criteria were fulfilled for 88.5% and 44.9% of all values, respectively. To conclude, iPro2 was more accurate; however, both sensors demonstrated inaccuracy at hypoglycemic range, highlighting the need for refinements in the current generation of sensors to address this problem.

Bone health in breast cancer.

Early breast cancer is among the most common cancers worldwide. Recent advances continue to improve outcomes and increase long-term survivorship. However, therapeutic modalities are deleterious for patients' bone health. While antiresorptive therapy may partially negate this, consequent reduction in rates of fragility fractures remains unproven. Selective prescription of bisphosphonates or denosumab may be an amicable middle ground. Recent evidence also suggests a possible role of osteoclast inhibitors as adjuvant therapy, but the evidence is modest at best. In this narrative clinical review, we explore the impact of various adjuvant modalities on bone mineral density and fragility fracture rates of early breast cancer survivors. We also review optimal patient selection for antiresorptive agents, their impact on rates of fragility fractures, and the possible role of these agents as adjuvant therapy.

Primary Mediastinal Germ Cell Tumors (PMGCT): A Real-world Analysis From A Tertiary Cancer Care Center in India.

BACKGROUND: Primary mediastinal GCT (PMGCT) is a rare entity and comprises 10-15% of all mediastinal tumors. We present our institutional experience of MGCT treated with multimodality management. MATERIALS AND METHODS: We conducted a retrospective analysis between 2010 to 2020 of all mediastinal germ cell tumors registered at our center. Data on patient demographics, treatments received, treatment toxicities and response were recorded. Overall survival and relapse free survival were estimated using Kaplan-Meier methods. RESULTS: A total of 30 patients were identified. The median age was 25.5 (range, 18-45) years. Common presenting features included cough (70%) and shortness of breath (70%). Histology wise, 60% patients were non seminomatous histology, whereas 33.3% patients were Seminoma. Twenty-seven (90%) patients received chemotherapy as the first-line treatment, of whom five patients (16.6%) underwent surgery and radiation therapy subsequently. Median follow-up was 26.9 months. Thirteen patients (43.3%) had complete response (43.3%) and eight patients had partial response (26.7%), while three patients (5.5%) had progressive disease. Three-year relapse-free survival rate was 69.6% (95% confidence interval [CI], 42.8-85.6%). Overall survival (OS) at 3 years was 73.4% (95% CI, 49.4-87.3%). Patients with seminoma had a 3 year OS of 90.0% (95% CI, 47.3-98.5%) compared to those with non-seminoma (63.53% [95% CI, 32.3-83.3%]). CONCLUSIONS: Multiagent chemotherapy is the backbone of treatment in PMGCT. Seminomatous PMGCT have excellent prognosis, while further improvement is needed in those with nonseminomatous tumor.

Dexamethasone-free antiemetic strategy for highly emetogenic chemotherapy: safety and efficacy-pilot study.

OBJECTIVES: Dexamethasone sparing strategies have shown success. The feasibility of a dexamethasone-free antiemetic strategy remains undetermined. A prospective, single-arm, pilot study was planned to determine the efficacy of an olanzapine-based, dexamethasone-free, three-drug antiemetic regimen. METHODS: Chemotherapy naïve, adult patients (≥18 years) who received ondansetron, aprepitant and olanzapine during the first cycle of highly emetogenic chemotherapy were enrolled. The primary endpoint was the rate of complete response (CR: no vomiting and no use of rescue medications) during the overall period (0-120 hours). RESULTS: Out of the total of 101 patients enrolled, most were women (82%) and received anthracycline cyclophosphamide (73%) combination therapy. The rate of CR for the overall period was 65% (95% CI 55.2% to 74.5%). The rate of CR for the acute and delayed period was 79% (95% CI 70% to 86.7%) and 76% (95% CI 66.7% to 84.1%). The rate of nausea control rates for the acute, delayed and overall periods were 34%, 29% and 24%, respectively. The grade I, II and III sedation rates over the 5 days were 8%, 5% and 1%, respectively. CONCLUSIONS: The dexamethasone-free antiemetic strategy showed modest efficacy with low incidence of clinically significant somnolence. There is a need to prospectively investigate the role of dexamethasone in the era of newer potent antiemetics in a randomised fashion. TRIAL REGISTRATION NUMBER: CTRI/2021/07/034813.

Langerhans Cell Histiocytosis of Bilateral Parotid and Submandibular Glands: Findings on 18F-FDG PET/CT.

ABSTRACT: Langerhans cell histiocytosis is a disorder of the mononuclear phagocytic system. Virtually any organ can be involved, the bone, skin, lungs, and pituitary gland being the most common. We describe the case of a 30-year-old man who presented with painless neck swelling. 18 F-FDG PET/CT showed bilateral bulky parotid and submandibular glands with increased metabolic activity. Histopathology confirmed the diagnosis of Langerhans cell histiocytosis. To our knowledge, there has been no description of 18 F-FDG PET/CT findings in Langerhans cell histiocytosis of salivary glands in literature. We aim to aid in the diagnosis and management of this rare presentation.

Prevalence of mental health problems in mothers of preterm infants admitted to NICU: A cross-sectional study.

OBJECTIVE: To study the prevalence of mental health problems among mothers of preterm infants admitted to the neonatal intensive care unit (NICU). METHODS: In this cross-sectional two-arm study, 130 mothers in each group, with either term infants not in NICU or preterm infants admitted to NICU, underwent mental health assessment using the Generalized Anxiety Disorder Scale, Centre for Epidemiologic Studies-Depression Scale, Stanford Acute Stress Reaction Questionnaire and Modified Parental Stress Scale-NICU. Their coping styles and quality of life were also assessed. Data were analyzed using SPSS IBM 25.0. RESULTS: Anxiety (66.2% versus 46.9%) and depression (45.4% versus 23.1%) were more common among NICU mothers. Regarding subdomains of acute stress reaction, a higher number of NICU mothers showed symptoms of anxiety, re-experience and functional impairment. For mothers with infants in NICU, sight, sound, and parental role alterations were stressful. They had reduced quality of life scores in domains of physical health, psychological health, and social relationships. Also, a higher number of these mothers exhibited problem-solving and emotion-focused coping. CONCLUSION: Preterm birth with NICU admission of the infant is more stressful for a mother than the term birth of a healthy neonate. It affects her mental health and quality of life. Both the obstetrician and the pediatrician should be mindful of this.

Real World Presentation and Treatment Outcomes with a Predominant Induction Chemotherapy Based Approach in Nasopharyngeal Carcinoma: A Sixteen Year Report from a Teaching Hospital in India.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a rare malignancy in India except in north-eastern states. We present our institutional experience of 16 years highlighting management, outcomes, responses and toxicities. MATERIALS AND METHODS: NPC patients registered at our center during the period of 2000-2015. The primary objective of the study was to assess the overall survival (OS). Secondary outcome included determinations of response rates, progression free survival (PFS) and to assess treatment-related toxicity (CTCAE v4.0). Institute ethics committee approval was obtained prior to initiation of this study. RESULTS: Data was retrieved from complete records of 222 patients out of 390 registered during study period. There were 163 males (73.4%) and 59 females (26.6%) with a male to female ratio of 2.8:1. The median age was 35 years (range 6-73). Only 5.6% (n = 12) presented in early-stage disease (stage I and II) while 89.6% (n = 199) were advanced stage (stage III, IVA, IVB). Five patients (2.2%) presented as metastatic disease. Majority of patients were treated with induction chemotherapy followed by concurrent chemoradiation (CCRT) {76.1%, n = 169}. Relapses were documented in 10.4% patients. 5% patients had loco-regional relapse while distant metastases were seen in 4% patients. The 3-year PFS and OS rates are 60.9% and 68.4%, respectively. Achieving a CR predicted superior OS on multivariate analysis. CONCLUSIONS: NPC is a rare malignancy and majority presented with advanced stages. This data outlines our experience and outcomes with a predominantly induction chemotherapy followed by definitive CCRT based approach.

Gut microbiome dysbiosis in the setting of solid organ transplantation: What we have gleaned from human and animal studies.

The human gut microbiome refers to all of the microorganisms present throughout the length of the gastrointestinal tract. Gut flora influence host metabolic and immune processes in myriad ways. They also play an important role in maturation and modulation of the immune system. Dysbiosis or a pathologic alteration in gut flora has been implicated in a number of diseases ranging from metabolic, autoimmune and degenerative. Whether dysbiosis has similar implications in organ transplant has been the focus of a number of pre-clinical and clinical studies. Researchers have observed significant microbiome changes after solid organ transplantation in humans that have been associated with clinical outcomes such as post-transplant urinary tract infections and diarrhea. In this article, we will discuss the available data regarding pathologic alterations in gut microbiome (dysbiosis) in solid organ transplant recipients as well as some of challenges in this field. We will also discuss animal studies focusing on mouse models of transplantation that shed light on the underlying mechanisms that explain these findings.

Impact of Prolonged Cold Ischemia Time on One Year Kidney Transplant Outcomes.

BACKGROUND: Prolonged cold ischemia times (CIT) of kidney allografts remains a significant reason for graft refusal in the new allocation system. We sought to investigate the effect of prolonged CIT on kidney transplant outcomes at a center without an international airport. METHODS: Retrospective study of kidney transplant patients treated at an academic medical center from January 1, 2018 to May 1, 2020. The 117 patients were divided into 2 categories. Fifty-four patients (46%) had CIT of 30-35.99 hours, and 63 (54%) had CIT of 36± hours. Kidney function was evaluated using creatinine and at 12 months, which was the primary endpoint. RESULTS: All of the transplanted allografts were carefully selected and had ≤ 20% glomerulosclerosis and an average kidney donor profile index of 54%. Among the 117 patients analyzed in this study, there was no significant difference in creatinine at 12 months between groups with CIT above 36 hours and < 35.99 hours (2.07 vs 1.78; P value .2339). There were a total of 18 rejection events (15%) and no cases of primary non-function in either group. Patients that were able to be maintained on calcineurin inhibitors had improved graft function at 12 months (1.69 vs 2.96; P value .0267). CONCLUSIONS: Our study indicated that prolonged CITs over 36 hours were not associated with poorer patient outcomes at 1 year when using creatinine as an endpoint. They also had similar rates of rejection, consistent with previously published rates for kidney transplantation.

Microbiomics for enhancing electron transfer in an electrochemical system.

In microbial electrochemical systems, microorganisms catalyze chemical reactions converting chemical energy present in organic and inorganic molecules into electrical energy. The concept of microbial electrochemistry has been gaining tremendous attention for the past two decades, mainly due to its numerous applications. This technology offers a wide range of applications in areas such as the environment, industries, and sensors. The biocatalysts governing the reactions could be cell secretion, cell component, or a whole cell. The electroactive bacteria can interact with insoluble materials such as electrodes for exchanging electrons through colonization and biofilm formation. Though biofilm formation is one of the major modes for extracellular electron transfer with the electrode, there are other few mechanisms through which the process can occur. Apart from biofilm formation electron exchange can take place through flavins, cytochromes, cell surface appendages, and other metabolites. The present article targets the various mechanisms of electron exchange for microbiome-induced electron transfer activity, proteins, and secretory molecules involved in the electron transfer. This review also focuses on various proteomics and genetics strategies implemented and developed to enhance the exo-electron transfer process in electroactive bacteria. Recent progress and reports on synthetic biology and genetic engineering in exploring the direct and indirect electron transfer phenomenon have also been emphasized.

Is menstruation a valid reason to postpone cardiac surgery?

Background: Cancellation of any scheduled surgery is a significant drain on health resources and potentially stressful for patients. It is frequent in menstruating women who are scheduled to undergo open heart surgery (OHS), based on the widespread belief that it increases surgical and menstrual blood loss. Aims: The aim of this study was to evaluate blood loss in women undergoing OHS during menstruation. Settings and Design: A prospective, matched case-control study which included sixty women of reproductive age group undergoing OHS. Patients and Methods: The surgical blood loss was compared between women who were menstruating (group-M; n = 25) and their matched controls, i.e., women who were not menstruating (group-NM; n = 25) at the time of OHS. Of the women in group M, the menstrual blood loss during preoperative (subgroup-P) and perioperative period (subgroup-PO) was compared to determine the effect of OHS on menstrual blood loss. Results: The surgical blood loss was comparable among women in both groups irrespective of ongoing menstruation (gr-M = 245.6 ± 120.1 ml vs gr-NM = 243.6 ± 129.9 ml, P value = 0.83). The menstrual blood loss was comparable between preoperative and perioperative period in terms of total menstrual blood loss (gr-P = 36.8 ± 4.8 ml vs gr-PO = 37.7 ± 5.0 ml, P value = 0.08) and duration of menstruation (gr-P = 4.2 ± 0.6 days vs gr-PO = 4.4 ± 0.6 days, P value = 0.10). Conclusion: Neither the surgical blood loss nor the menstrual blood loss is increased in women undergoing OHS during menstruation.

Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis.

IMPORTANCE: Carboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial. METHODS: The study was prospectively registered at PROSPERO (CRD42021228386). We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes. RESULTS: Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I2 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I2 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44-3.08; I2 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm. CONCLUSION: and relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.