Early evaluation of a next-generation surgical system in robot-assisted total laparoscopic hysterectomy: A prospective clinical cohort study.

INTRODUCTION: This study aimed to demonstrate the safe and effective use of the Versius surgical system (CMR Surgical, Cambridge, UK) in robot-assisted total laparoscopic hysterectomy. This surgical robot was developed iteratively with input from surgeons to improve surgical outcomes and end-user experience. We report data from the gynecology cohort of an early clinical trial designed in broad alignment with IDEAL-D (Idea, Development, Exploration, Assessment, Long-term follow-up - Devices) stage 2b (Exploration). MATERIAL AND METHODS: The study is registered in the Indian clinical trials register (CTRI/2019/02/017872). Adult women requiring total hysterectomy who provided informed consent and met the eligibility criteria underwent procedures at one of three hospitals in India. Five surgeons performed robot-assisted total laparoscopic hysterectomies using the device from March 2019 to September 2020. The primary endpoint was rate of unplanned conversion to conventional laparoscopic or open surgery. Adverse events were adjudicated by an independent clinical events committee using endoscope video recordings and clinical notes. RESULTS: In total, 144 women underwent surgery (median age: 44 years [range: 28-78]; median body mass index 25.8 kg/m2 [range: 14.3-47.8]). The rate of unplanned conversion to conventional laparoscopy was 2/144 (1.4%); neither conversion was device related. No surgery was converted to open. In total, 13 adverse events occurred among seven (4.9%) patients, comprising seven serious adverse events and six adverse events. One serious adverse event was deemed device-related. Two patients were readmitted to hospital within 30 days; both made a full recovery. No patients died within 90 days of surgery. CONCLUSIONS: The device provides a safe and effective option for total laparoscopic hysterectomy; these findings support its continued implementation in larger patient cohorts and expansion in other major minimal access indications.

Interim safety analysis of the first-in-human clinical trial of the Versius surgical system, a new robot-assisted device for use in minimal access surgery.

OBJECTIVE: The aim of this study was to provide an interim safety analysis of the first 30 surgical procedures performed using the Versius Surgical System. BACKGROUND: Robot-assisted laparoscopy has been developed to overcome some of the important limitations of conventional laparoscopy. The new system is currently undergoing a first-in-human prospective clinical trial to confirm the safety and effectiveness of the device when performing minimal access surgery (MAS). METHODS: Procedures were performed using Versius by a lead surgeon supported by an operating room (OR) team. Male or female patients aged between 18 and 65 years old and requiring elective minor or intermediate gynaecological or general surgical procedures were enrolled. The primary endpoint was the rate of unplanned conversion of procedures to other MAS or open surgery. RESULTS: The procedures included nine cholecystectomies, six robot-assisted total laparoscopic hysterectomies, four appendectomies, five diagnostic laparoscopy cases, two oophorectomies, two fallopian tube recanalisation procedures, an ovarian cystectomy and a salpingo-oophorectomy procedure. All procedures were completed successfully without the need for conversion to MAS or open surgery. No patient returned to the OR within 24 h of surgery and readmittance rate at 30 and 90 days post-surgery was 1/30 (3.3%) and 2/30 (6.7%), respectively. CONCLUSIONS: This first-in-human interim safety analysis demonstrates that the Versius Surgical System is safe and can be used to successfully perform minor or intermediate gynaecological and general surgery procedures. The cases presented here provide evidence that the Versius clinical trial can continue to extend recruitment and begin to include major procedures, in alignment with the IDEAL-D Framework Stage 2b: Exploration.

Experiences from Garbha-Swasthya helpline.

Garbha-Swasthya helpline is a telephone helpline run by a tertiary care private hospital to address issues related to pregnancy and its complications. A review of the helpline data from September 2010 to December 2012 was conducted to study caller characteristics, number of calls and related information, and the reasons to call. Out of the total 696 voice calls, 421 were new callers and 275 were repeat callers and they comprised mainly pregnant women (73.3%), their relatives (24.8%), and medical professionals (1.9%). Most calls were related to first pregnancy and were mainly from Pune and other cities of Maharashtra. All calls by the medical professionals were regarding drug safety in pregnancy. The commonest category of questions (27.4%) was about exposures (drugs, alcohol, eclipse, radiation, etc.) and preexisting medical illness followed by pregnancy complications (18.5%), common medical issues such as nausea/vomiting during pregnancy, and delivery and postpartum period (14% each). Although the total number of calls received has steadily increased, efforts to create public and professional awareness to increase the usage of this helpline are warranted.

Is germline transmission of MAD2 gene deletion associated with human fetal loss?

The spindle assembly checkpoint (SAC) monitors proper attachment of spindles to the kinetochore during mitotic and meiotic cell divisions and thus prevents aneuploidy. Chromosomal aneuploidy has been found to be associated with pregnancy loss and birth defects. Mad2 is one of the critical molecules of SAC. Deregulated Mad2 expression has been found to be associated with defective SAC-mediated abnormal meiotic progression in cell studies using animal models. Whether mutation in MAD2L1 is associated with the loss of Mad2 expression in aborted human fetuses is unknown. In this study, a correlation between aneuploidy and MAD2 defect was examined in primary fibroblast cultures obtained from abortuses. We report three trisomic abortuses with undetectable Mad2 expression. Further, quantitative real-time PCR revealed copy number deletion of MAD2 gene in these fetuses. Analysis of parental DNA samples available from two families revealed copy number loss of the same gene, suggesting Mendelian inheritance of MAD2 deletion. This germline transmission of exonic deletion of MAD2 is possibly associated with its loss of expression resulting in abnormal SAC function, subsequent aneuploidy and pregnancy loss.

Thrombolysis in the era of intervention.

Thrombolysis revolutionized the treatment of acute ST - elevation myocardial infarction in the latter part of the last century and has been in use for more than two decades. Use of thrombolytic therapy is widespread owing to its safety, efficacy, ease of use, and affordability. Thrombolytic therapy has several limitations, many of which have been overcome with the adoption of percutaneous coronary intervention techniques in recent years. Primary percutaneous intervention is currently the preferred form of reperfusion therapy in the management of ST elevation myocardial infarction. However, thrombolytic therapy continues to have a role in many situations even in this era of intervention.

A Multicenter, Randomized, Equivalence Trial of a New Recombinant Human Chorionic Gonadotropin Preparation versus Ovitrelle® for Ovulation in Women Undergoing Intrauterine Insemination Following Ovarian Stimulation.

CONTEXT: A new indigenous recombinant human chorionic gonadotropin (r-hCG) has been developed in India with a comparable pharmacological profile to that of Ovitrelle® (Merck Serono). AIMS: This study aims to compare the efficacy and safety of the new r-hCG with that of Ovitrelle for induction of ovulation in women undergoing intrauterine insemination (IUI). SETTINGS AND DESIGN: Randomized (2:1), multicenter, open-label, equivalence clinical trial conducted in India. SUBJECTS AND METHODS: A total of 217 women, aged 20-37 years, undergoing IUI were administered the new r-hCG (test) 250 mcg or Ovitrelle 250 mcg (comparator) after ovarian stimulation with gonadotropins. The ovulation rate was compared as the primary outcome. In addition, pregnancy rates, incidence of adverse events (AEs), and development of immunogenicity were assessed. Statistical Analysis Used: The ovulation and pregnancy rates were compared using Chi-squared test with statistical significance at P < 0.05. RESULTS: With 144 women in the test group and 73 in the comparator group, the ovulation rate (85.4% vs. 78.1%; P = 0.17) and pregnancy rate (serum ß hCG test) (11.8% vs. 12.3%; P = 0.91) were similar in both groups. A total of 15 AEs were reported (11 in the test r-hCG group and 4 in the comparator group) in 11 women; none of these were serious, and all were judged to be unrelated to the study drug. No subject developed immunogenic reaction to the test drug. CONCLUSIONS: The new preparation of r-hCG was equivalent to the conventional preparation of r-HCG in the induction of ovulation in patients undergoing IUI.

Bartsocas-Papas syndrome.

We report three sibs born to a third degree consanguineous Indian family affected with Bartsocas Papas Syndrome. All the three pregnancies were complicated by severe oligohydramnios, which is not commonly seen with Bartsocas-Papas syndrome.

Maternal Serum Aneuploidy Screen and Adverse Pregnancy Outcomes.

OBJECTIVE: To find out whether maternal serum screening for fetal chromosomal aneuploidy predicts adverse pregnancy outcomes. METHODS: A two-year retrospective case-control study was conducted at a tertiary hospital. Pregnant women with a high-risk serum screen but with chromosomally normal fetuses (n = 189) were compared to those with low-risk screen (controls, n = 157) for adverse pregnancy outcomes. RESULTS: Women with high-risk double marker or combined screen were found to have higher prevalence of LBW [OR 2.56; 95 % CI (1.01-6.53), p < 0.05] and PT [OR 2.93; 95 % CI (1.11-7.65), p < 0.05], while women with high-risk triple screen had higher prevalence of PIH [OR 3.72; 95 % CI (1.23-11.18); p < 0.05], Oligo [OR 4.50; 95 % CI (1.30-15.64); p < 0.05], delivery by C-section [OR 2.51; 95 % CI (1.41-4.47); p < 0.005] as compared to low-risk women. PAPP-A was found to be a significant predictor of birth weight (R (2) = 12.2 %, ß ± SE = 0.224 ± 0.069; p < 0.005) and gestational age (R (2) = 4.9 %, ß ± SE = 0.613 ± 0.296; p < 0.05). Beta hCG in first and hCG in second trimester predicted oligohydramnios (R (2) = 9.2 %, ß ± SE = -0.077 ± 0.025; p < 0.005). The areas under the ROC curves of PAPP-A for LBW and PT were 0.70(p < 0.01) and 0.684 (p < 0.05), respectively. CONCLUSION: A "high-risk" maternal serum screen with abnormal PAPP-A and/or beta hCG/HCG is associated with adverse pregnancy outcomes and may help identifying women requiring additional fetal surveillance.

Correction: Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175.

[This corrects the article DOI: 10.1371/journal.pone.0117820.].

Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175.

BACKGROUND: A phase I randomised, controlled, single blind, dose escalation trial was conducted to evaluate safety and immunogenicity of JAIVAC-1, a recombinant blood stage vaccine candidate against Plasmodium falciparum malaria, composed of a physical mixture of two recombinant proteins, PfMSP-1(19), the 19 kD conserved, C-terminal region of PfMSP-1 and PfF2 the receptor-binding F2 domain of EBA175. METHOD: Healthy malaria naïve Indian male subjects aged 18-45 years were recruited from the volunteer database of study site. Fifteen subjects in each cohort, randomised in a ratio of 2:1 and meeting the protocol specific eligibility criteria, were vaccinated either with three doses (10 µg, 25 µg and 50 µg of each antigen) of JAIVAC-1 formulated with adjuvant Montanide ISA 720 or with standard dosage of Hepatitis B vaccine. Each subject received the assigned vaccine in the deltoid muscle of the upper arms on Day 0, Day 28 and Day 180. RESULTS: JAIVAC-1 was well tolerated and no serious adverse event was observed. All JAIVAC-1 subjects sero-converted for PfF2 but elicited poor immune response to PfMSP-1(19). Dose-response relationship was observed between vaccine dose of PfF2 and antibody response. The antibodies against PfF2 were predominantly of IgG1 and IgG3 isotype. Sera from JAIVAC-1 subjects reacted with late schizonts in a punctate pattern in immunofluorescence assays. Purified IgG from JAIVAC-1 sera displayed significant growth inhibitory activity against Plasmodium falciparum CAMP strain. CONCLUSION: Antigen PfF2 should be retained as a component of a recombinant malaria vaccine but PfMSP-1(19) construct needs to be optimised to improve its immunogenicity. TRIAL REGISTRATION: Clinical Trial Registry, India CTRI/2010/091/000301.