Comparative Analysis of Performance of Large Language Models in Urogynecology.

IMPORTANCE: Despite growing popularity in medicine, data on large language models in urogynecology are lacking. OBJECTIVE: The aim of this study was to compare the performance of ChatGPT-3.5, GPT-4, and Bard on the American Urogynecologic Society self-assessment examination. STUDY DESIGN: The examination features 185 questions with a passing score of 80. We tested 3 models-ChatGPT-3.5, GPT-4, and Bard on every question. Dedicated accounts enabled controlled comparisons. Questions with prompts were inputted into each model's interface, and responses were evaluated for correctness, logical reasoning behind answer choice, and sourcing. Data on subcategory, question type, correctness rate, question difficulty, and reference quality were noted. The Fisher exact or χ2 test was used for statistical analysis. RESULTS: Out of 185 questions, GPT-4 answered 61.6% questions correctly compared with 54.6% for GPT-3.5 and 42.7% for Bard. GPT-4 answered all questions, whereas GPT-3.5 and Bard declined to answer 4 and 25 questions, respectively. All models demonstrated logical reasoning in their correct responses. Performance of all large language models was inversely proportional to the difficulty level of the questions. Bard referenced sources 97.5% of the time, more often than GPT-4 (83.3%) and GPT-3.5 (39%). GPT-3.5 cited books and websites, whereas GPT-4 and Bard additionally cited journal articles and society guidelines. Median journal impact factor and number of citations were 3.6 with 20 citations for GPT-4 and 2.6 with 25 citations for Bard. CONCLUSIONS: Although GPT-4 outperformed GPT-3.5 and Bard, none of the models achieved a passing score. Clinicians should use language models cautiously in patient care scenarios until more evidence emerges.

Rate of deterioration of umbilical artery Doppler indices in fetuses with severe early-onset fetal growth restriction.

BACKGROUND: Incorporation of umbilical artery Doppler in the surveillance of fetal growth restriction has been shown to reduce the risk of perinatal deaths. Systole/Diastole ratio, Pulsatility Index and Resistance Index are obtained upon Doppler interrogation of the umbilical artery however it is unknown which index predicts more advanced stages of placental deterioration. OBJECTIVE: This study aimed to examine risk factors for the development of absent or reversed end-diastolic velocity and the time intervals of deterioration from normal umbilical artery end-diastolic velocity (indicated by systole/diastole ratio, pulsatility index, or resistance index) to decreased and absent or reversed end-diastolic velocity in fetuses with early-onset severe fetal growth restriction. STUDY DESIGN: This was a retrospective cohort study performed from 2005 to 2020. All singleton pregnancies with severe (estimated fetal weight or abdominal circumference below the third percentile) and early-onset (diagnosed between 20 0/7 and 31 6/7 weeks of gestation) fetal growth restriction were included. Patients with fetal genetic or structural anomalies, suspected congenital infections, absent or reversed end-diastolic velocity at diagnosis, poor pregnancy dating, and absence of follow-up ultrasounds were excluded. Estimated fetal weight, abdominal circumference, and Doppler indices were reviewed longitudinally from diagnosis to delivery. To examine risk factors for absent or reversed end-diastolic velocity, we performed backward stepwise logistic regression and calculated odds ratios with 95% confidence intervals. Kaplan-Meier curves were compared using log-rank tests. RESULTS: A total of 985 patients met the inclusion criteria, and 79 (8%) progressed to absent or reversed end-diastolic velocity. Factors associated with development of absent or reversed end-diastolic velocity included gestational age at diagnosis (adjusted odds ratio, 4.88 [95% confidence interval, 2.55-9.37] at 20 0/7 to 23 6/7 weeks; adjusted odds ratio, 1.56 [95% confidence interval, 0.86-2.82] at 24 0/7 to 27 6/7 weeks compared with 28 0/7 to 31 6/7 weeks) and presence of chronic hypertension (adjusted odds ratio, 2.37 [95% confidence interval, 1.33-4.23]). Rates of progression from diagnosis of fetal growth restriction with normal umbilical artery Doppler to absent or reversed end-diastolic velocity were significant after 4 weeks from diagnosis (5.84% [95% confidence interval, 4.50-7.57]). Regarding the Doppler indices, the progression from normal values to abnormal indices was similar at 1 and 2 weeks. However, the rate of progression from normal to abnormal systole/diastole ratio compared with the rates of progression from normal to abnormal pulsatility index or resistance index was higher at 4 and 6 weeks. Deterioration from abnormal indices to absent or reversed end-diastolic velocity was shorter with abnormal resistance index and pulsatility index when compared with the systole/diastole ratio at 2, 4, and 6 weeks after diagnosis and at 6 weeks, respectively. CONCLUSION: Earlier gestational age at diagnosis and chronic hypertension are considered as risk factors for Doppler deterioration and development of absent or reversed end-diastolic velocity in the umbilical artery. With normal Doppler indices, significant deterioration and progression to absent or reversed end-diastolic velocity is unlikely until 4 weeks after diagnosis. Abnormal systole/diastole ratio seems to appear first. However, abnormal pulsatility index or resistance index was associated with absent or reversed end-diastolic velocity.

Prospective observational study to validate a next-generation sequencing blood RNA signature to predict early kidney transplant rejection.

The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post-kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a nonrandomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia + serum creatinine at biopsy. Of the 151 kidney transplant recipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia + creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100) generated a high- and low-risk category for AR with a negative predictive value of 0.79 (95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odds ratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.

Dose-Dense Chemotherapy Regimen for Breast Cancer Associated with Significant Decline in Ovarian Reserve.

Purpose: To determine the impact of dose-dense chemotherapy administration on ovarian reserve in women undergoing treatment for breast cancer. Patients and Methods: We conducted a retrospective cohort study of reproductive age women who underwent dose-dense chemotherapy regimens with doxorubicin hydrochloride and cyclophosphamide with or without paclitaxel for a new diagnosis of breast cancer. We compared pre- and post-treatment serum antimullerian hormone (AMH) levels and assessed changes in AMH over time. Results: Fifty-seven patients met inclusion criteria. Median pre-treatment AMH was 2.9 ng/mL, whereas post-treatment AMH was 0.1 ng/mL, demonstrating a dramatic reduction in AMH levels after treatment with a dose-dense regimen. This change was independent of age and was sustained over 12 months from treatment completion. Conclusions: Dose-dense chemotherapy regimens for breast cancer lead to marked and sustained decreases in AMH irrespective of patient age.

Robotic-assisted vaginal natural orifice transluminal endoscopic surgery versus robotic-assisted single-site port for benign hysterectomy: a comparison of surgical outcomes.

The objective of this study is to evaluate the surgical outcomes for robotic-assisted vaginal natural orifice transluminal endoscopic surgery (R-VNOTES) hysterectomy versus robotic-assisted single-site port (RSSP) hysterectomy when performed for benign indications. This is a retrospective chart review in an academic tertiary setting. 404 patients underwent hysterectomy for benign indications. R-VNOTES hysterectomy and RSSP hysterectomy were performed by a single minimally invasive gynecologic surgeon from January 2015 to August 2022. The primary outcome of our study was total operative time (minutes). Secondary outcomes included estimated blood loss (mL), length of hospital stay (days), and postoperative pain score. Other intraoperative and postoperative surgical complications were also compared. 159 patients underwent R-VNOTES hysterectomy, and 269 patients underwent RSSP hysterectomy. Median length of surgery (minutes) demonstrated a statistically significant shorter operative time in the R-VNOTES hysterectomy group when compared to the RSSP hysterectomy group, (132 min versus 146 min, respectively, p = 0.0001). Additionally, patients in the R-VNOTES hysterectomy group experienced decreased postoperative pain levels at week 1 (6 versus 7, respectively, p = 0.01) and week 3 (1.5 versus 2.5, respectively, p = 0.01) after surgery. There were no statistically significant differences between the two groups when comparing length of hospital stay, estimated blood loss, and weight of the uterus. There was no difference in rates of urinary tract infection, blood transfusion, bowel injury, readmission, reoperation, conversion, deep surgical site infection, and venous thromboembolism between both groups. However, there was a higher rate of superficial SSI in the RSSP hysterectomy group (0.6% versus 4.5%, respectively, p = 0.03). When compared to RSSP hysterectomy, R-VNOTES hysterectomy is safe and feasible, as both approaches have comparable surgical outcomes. Patients undergoing R-VNOTES hysterectomy had shorter length of surgery, decreased postoperative pain, and lower rates of superficial surgical site infections.

Use of a pocket-device point-of-care ultrasound to assess cervical dilation in labor: correlation and patient experience.

OBJECTIVES: To estimate the correlation of cervical dilation between pocket-device point-of-care transperineal ultrasound (TPUS) and digital cervical examination (DCE). METHODS: Laboring pregnant individuals ≥37 weeks of gestation presenting were prospectively evaluated for cervical dilation with a handheld pocket-sized ultrasound (Butterfly iQ+®) applied to the perineum, with a blinded DCE directly following. Subjects completed a survey to rate pain and for any preference from the examinations. To detect a moderate correlation (r=0.5) between TPUS and DCE, with an alpha of 0.05 and power of 80%, a sample size of 30 examinations were needed. RESULTS: From April 2022 to July 2022, 30 pregnant individuals were assessed. The median cervical dilation by TPUS vs. DCE was 5.1 and 5 cm, respectively, with a Pearson's correlation coefficient, r=0.86 (95% CI 0.72 to 0.93), p<0.001. Transperineal ultrasound had a significantly less pain score than DCE, median pain score 0 vs. 2 for TPUS and DCE respectively, p<0.001. All individuals preferred the TPUS over the DCE. CONCLUSIONS: Measurement of cervical dilation using a pocket-device point-of-care TPUS has a strong positive correlation with DCE and offers a non-invasive, convenient alternative to traditional digital exams in term, laboring patients.

A pilot study of the role of the claustrum in attention and seizures in rats.

OBJECTIVE: The claustrum has been implicated in consciousness, and MRIs of patients with status epilepticus have shown increased claustral signal intensity. In an attempt to investigate the role of claustrum in cognition and seizures, we (1) assessed the effect of high-frequency stimulation (HFS) of the claustrum on performance in the operant chamber; (2) studied interclaustral and claustrohippocampal connectivity through cerebro-cerebral evoked potentials (CCEPs); and (3) investigated the role of claustrum in kainate-induced (KA) seizures. METHODS: Adult male Sprague-Dawley rats were trained in operant conditioning and implanted with electrodes in bilateral claustra and hippocampi. Claustrum HFS (50 Hz) was delivered bilaterally and unilaterally with increasing intensities from 50 to 1000 µA, and performance scores were assessed. CCEPs were studied by averaging the responses to bipolar stimulations, 1-ms wide pulses at 0.1 Hz to the claustrum. KA seizures were analyzed on video-EEG recordings. RESULTS: Generalized Estimating Equations analysis revealed that claustral stimulation reduced task performance scores relative to rest sessions (bilateral: -15.8 percentage points, p < 0.0001; unilateral: -15.2, p < 0.0001). With some stimulations, the rats showed a stimulus-locked decrease in attentiveness and, occasionally, an inability to complete the operant task. CCEPs demonstrated interclaustral and claustrohippocampal connectivity. Some KA seizures appeared to originate from the claustrum. CONCLUSIONS: Findings from the operant conditioning task suggest stimulation of the claustrum can alter attention or awareness. CCEPs demonstrated connectivity between the two claustra and between the claustrum and the hippocampi. Such connectivity may be part of the circuitry that underlies the alteration of awareness in limbic seizures. Lastly, KA seizures showed early involvement of the claustrum, a finding that also supports a possible role of the claustrum in the alteration of consciousness that accompanies dyscognitive seizures.

Herpes simplex virus-2 transmission following solid organ transplantation: Donor-derived infection and transplantation from prior organ recipients.

BACKGROUND: Owing to limited availability of donor organs, previous solid organ transplant (SOT) recipients are increasingly considered as potential organ donors. We report donor-derived transmission of herpes simplex virus type-2 (HSV-2) to two clusters of SOT recipients with transmission from the original donor and an HSV-2-infected recipient who subsequently became a donor. METHODS: We reviewed medical records of the donors and recipients in both clusters. Pre-transplant serology and virological features of HSV-2 were characterized. Genotyping of HSV-2 isolates to determine potential for donor transmission of HSV-2 through transplantation of organs from prior organ recipients was performed. RESULTS: A kidney-pancreas recipient died day 9 post transplant. Following confirmation of brain death, the lungs and recently transplanted kidney were donated to two further recipients. The liver was not retrieved, but biopsy confirmed HSV-2 infection. Testing on the original donor showed negative HSV-2 polymerase chain reaction and HSV immunoglobulin (Ig)M, but positive HSV-2 IgG. The liver recipient from the original donor developed HSV-2 hepatitis and cutaneous infection that responded to treatment with intravenous acyclovir. In the second cluster, lung and kidney recipients both developed HSV-2 viremia that was successfully treated with antiviral therapy. Genotyping of all HSV-2-positive samples showed 100% sequence homology for three recipients. CONCLUSIONS: Donor-derived HSV infection affected two clusters of recipients because of transplantation of organs from a prior organ recipient. HSV should be considered as a possible cause of illness in febrile SOT recipients in the immediate post-transplant period and may cause disseminated disease and re-infection in HSV-2-seropositive recipients. Testing of HSV serology and prophylaxis may be considered in SOT recipients not receiving cytomegalovirus prophylaxis.

Effects of low-frequency electrical stimulation of the anterior piriform cortex on kainate-induced seizures in rats.

OBJECTIVE: Recent evidence in animals and humans suggests that low-frequency stimulation (LFS) has significant antiepileptic properties. The anterior piriform cortex (APC) is a highly susceptible seizure-trigger zone and may be critical for the initiation and propagation of seizures originating from cortical and limbic foci. We used the kainic acid (KA) seizure model in rats to assess the therapeutic effect of LFS of the APC on seizures. METHODS: Adult male Sprague-Dawley rats were implanted with electrodes in the left APC and recording electrodes bilaterally in the hippocampal CA3 regions. Rats were monitored continuously with video-EEG after the emergence of spontaneous recurrent seizures that followed induction of status epilepticus by intraperitoneal KA. After two weeks of baseline recordings to determine seizure frequency, LFS of the APC was applied 60-min On 15-min Off, for two weeks with 1Hz biphasic square waves, 0.2ms pulse width, at 200µA. Another 2-week period of video-EEG monitoring was done after the cessation of LFS to study the carry-over effect. Changes in seizure frequency, severity, and duration between baseline, during LFS, and post-LFS were analyzed using the Poisson regression model. RESULTS: Overall seizure frequency decreased during the post-LFS period to 5% of that at baseline (p=0.003). Severe seizures (stages 4 and 5 on the Racine scale) decreased to 0% of the baseline during the post-LFS period. CONCLUSIONS: Two weeks of LFS of the APC reduced spontaneous seizure frequency and severity in the KA model with the effect outlasting the stimulation. Our findings suggest that the APC can be an important therapeutic target for stimulation in epilepsy.

Acute and spontaneous seizure onset zones in the intraperitoneal kainic acid model.

OBJECTIVE: Hippocampal monitoring is often used in the intraperitoneal kainic acid (KA) seizure model for detection and quantification of early ictal activity. Here, we investigated extra-hippocampal seizure onset zones (SOZs) in this model. METHODS: Eight male Sprague Dawley rats implanted with depth electrodes were continuously recorded during intraperitoneal KA injections until status epilepticus (SE) was induced. Another group of four rats was monitored chronically up to two weeks after emergence of spontaneous recurrent seizures. All rats had hippocampal electrodes. Other sampled brain regions included, among others, the claustrum, piriform cortex, and orbital cortex. Seizures recorded with video-EEG were visually analyzed. RESULTS: In the 58 seizures recorded during KA injections, the SOZ was extrahippocampal in 7 (12%), diffuse in 29 (50%), and hippocampal in 22 (38%). Of the 14 spontaneous seizures recorded, none were solely extrahippocampal, 10 (71%) were diffuse, and 4 (29%) were of hippocampal onset. All extra-hippocampal seizures propagated to the hippocampus within 4 to 50s (mean=14, n=7). No distinctive semiological manifestations correlated with the SOZs. SIGNIFICANCE: We conclude that seizures can have multifocal SOZs in the KA model. This finding is important to consider when using this model, among other purposes, to screen for new therapies, study pharmacoresistance, or investigate comorbidities of epilepsy.

Production of homozygous alpha-1,3-galactosyltransferase knockout pigs by breeding and somatic cell nuclear transfer.

We report here our experience regarding the production of double or homozygous Gal knockout (Gal KO) pigs by breeding and somatic cell nuclear transfer (SCNT). Large White x Landrace female heterozygous Gal KO founders produced using SCNT were mated with Hampshire or Duroc males to produce a F1 generation. F1 heterozygous pigs were then bred to half-sibs to produce a F2 generation which contained Gal KO pigs. To determine the viability of mating Gal KO pigs with each other, one female F2 Gal KO pig was bred to a half-sib and subsequently a full-sib Gal KO. F1 and F2 heterozygous females were also mated to F2 Gal KO males. All three types of matings produced Gal KO pigs. To produce Gal KO pigs by SCNT, heterozygous F1s were bred together and F2 fetuses were harvested to establish primary cultures of Gal KO fetal fibroblasts. Gal KO embryos were transferred to five recipients, one of which became pregnant and had a litter of four piglets. Together our results demonstrate that Gal KO pigs can be produced by breeding with each other and by SCNT using Gal KO fetal fibroblasts.

Characterization of the swine major histocompatibility complex alleles at eight loci in Westran pigs.

BACKGROUND: Pigs are an important large animal model for transplantation and a potential source of xenografts. Swine leukocyte antigen (SLA) molecules are strong mediators of alloreactive and xenoreactive immune responses. We have characterized the SLA alleles of a new pig line bred for transplantation research, the Westran (Westmead Hospital transplantation) pig, described in a companion paper. METHODS: Three sixth generation inbred Westran pigs and a Large White pig control were used to assess SLA alleles. We examined the SLA-1, SLA-3, SLA-6, SLA-2, DQA1, DQB1, DRA1 and DRB1 loci using reverse transcription-polymerase chain reaction and sequencing-based method. RESULTS: All of the Westran pigs had a single allele at each locus, except for the SLA-1 locus. Typing of the SLA-1 locus in additional animals indicated that this is most likely the result of a duplication of the SLA-1 locus rather than heterozygosity. The lack of SLA heterozygosity is consistent with the previous finding of low microsatellite marker heterozygosity and is the result of both the recent deliberate inbreeding of these pigs and their derivation from a feral stock from Kangaroo Island, South Australia, established by the release of a single pair in 1803. CONCLUSIONS: After comparing DNA and protein sequences of the Westran SLA alleles with published GenBank SLA sequences, the SLA class I alleles found in the Westran pigs were all novel, while the SLA-DR and DQB1 alleles have been previously described in other pig breeds. Characterization of the SLA alleles in the Westran pigs has identified novel alleles and will be useful for designing protocols for modulation of immune responses to allografts and xenografts.

Responses against complex antigens in various models of CD4 T-cell deficiency: surprises from an anti-CD4 antibody transgenic mouse.

The most common models of CD4 T-cell deficiency are mice exogenously injected with anti-CD4 antibody (Ab), CD4 knockout (CD4-/-) and major histocompatibility complex (MHC) class II knockout (class II-/-) mice. We recently described the anti-CD4 Ab transgenic mouse (GK) as an improved CD4 cell-deficient model. This review compares this new GK mouse model with the widely available class II-/- and CD4-/- mice, when exposed to complex antigens (foreign grafts and during bacterial or viral infection). We highlight here the cytometric and functional differences (including Ab isotype, viral or bacterial clearance, and graft survival) among these CD4 cell-deficient models. For example, whereas grafts are generally rejected in class II-/- and CD4-/- mice as quickly as in wild-type mice, they survive longer in GK mice. Also, CD4-/- mice produce IgG against both simple model and complex antigens, but class II-/- and GK mice produce small amounts of IgG2a against complex antigens but not simple model antigens. These differences harbinger the caveats in the use of these various mice.

Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: toxicity and clinical outcome.

PURPOSE: To assess the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) in pancreatic and bile duct (cholangiocarcinoma) malignancies. METHODS AND MATERIALS: Twenty-five patients with pancreatic and bile duct cancer were treated with IMRT. Twenty-three received concurrent 5-fluoruracil. One patient with a pancreatic primitive neuroectodermal tumor received concurrent etoposide and ifosfamide. Eight patients had resected tumors, and 17 had unresectable primary (n = 14) or recurrent (n = 3) tumors. Six patients underwent treatment planning with conventional three-dimensional four-field techniques for dosimetric comparison with IMRT. RESULTS: Compared with conventional RT, IMRT reduced the mean dose to the liver, kidneys, stomach, and small bowel. IMRT was well tolerated, with 80% experiencing Grade 2 or less acute upper GI toxicity. At a median follow-up of 10.2 months, no resected patients had local failure, and only 1 of 10 assessable patients with unresectable cancer had local progression. The median survival and distant metastasis-free survival of the 24 patients with adenocarcinoma was 13.4 and 7.3 months, respectively. Grade 4 late liver toxicity occurred in 1 patient surviving >5 years. The remainder of the assessable patients experienced no (n = 9) or Grade 1 (n = 4) late toxicity. CONCLUSION: In this hypothesis-generating analysis, the acute and chronic toxicity profile with IMRT in the treatment of pancreatic and bile duct cancer was encouraging. Local control was not compromised, despite efforts to increase conformality and avoid doses to normal structures. Distant failure remains a major obstacle in pancreatic cancer.

Impact of hormone therapy when combined with external beam radiotherapy for early-stage, intermediate-, or high-risk prostate cancer.

The purpose of this investigation was to explore the potential benefit of hormone therapy in addition to external beam radiotherapy for patients with early-stage (T1-2), intermediate-(prostate-specific antigen [PSA] > 10 or Gleason score >or= 7) or high-risk (PSA > 10 and Gleason score >or= 7) prostate cancer. The charts of 412 patients with early-stage intermediate- and high-risk prostate cancer treated with external beam radiotherapy with or without a 4-month total androgen blockade were reviewed. The groups were balanced with respect to age, pretreatment PSA, and stage, but differed with respect to Gleason score and radiation dose. Biochemical failure rates, as defined by the ASTRO consensus panel, were compared between those receiving and those not receiving hormones. With a median follow-up of 2.0 years, the biochemical failure rate was 12.1 versus 23.1% (p = 0.02) in favor of those receiving hormones. This difference was seen for the subgroups followed for more than 6 months (12.5 vs. 25.0%), more than 9 months (14.5 vs. 26.3%), and more than 12 months (17.3 vs. 27.0%). Thus, biochemical failure decreased with the administration of hormone therapy in this group of patients with early stage, intermediate- or high-risk prostate cancer. This finding requires validation by ongoing randomized trials.