GroEL/ES chaperonin modulates the mechanism and accelerates the rate of TIM-barrel domain folding.

The GroEL/ES chaperonin system functions as a protein folding cage. Many obligate substrates of GroEL share the (ßα)8 TIM-barrel fold, but how the chaperonin promotes folding of these proteins is not known. Here, we analyzed the folding of DapA at peptide resolution using hydrogen/deuterium exchange and mass spectrometry. During spontaneous folding, all elements of the DapA TIM barrel acquire structure simultaneously in a process associated with a long search time. In contrast, GroEL/ES accelerates folding more than 30-fold by catalyzing segmental structure formation in the TIM barrel. Segmental structure formation is also observed during the fast spontaneous folding of a structural homolog of DapA from a bacterium that lacks GroEL/ES. Thus, chaperonin independence correlates with folding properties otherwise enforced by protein confinement in the GroEL/ES cage. We suggest that folding catalysis by GroEL/ES is required by a set of proteins to reach native state at a biologically relevant timescale, avoiding aggregation or degradation.

PARK2 Depletion Connects Energy and Oxidative Stress to PI3K/Akt Activation via PTEN S-Nitrosylation.

PARK2 is a gene implicated in disease states with opposing responses in cell fate determination, yet its contribution in pro-survival signaling is largely unknown. Here we show that PARK2 is altered in over a third of all human cancers, and its depletion results in enhanced phosphatidylinositol 3-kinase/Akt (PI3K/Akt) activation and increased vulnerability to PI3K/Akt/mTOR inhibitors. PARK2 depletion contributes to AMPK-mediated activation of endothelial nitric oxide synthase (eNOS), enhanced levels of reactive oxygen species, and a concomitant increase in oxidized nitric oxide levels, thereby promoting the inhibition of PTEN by S-nitrosylation and ubiquitination. Notably, AMPK activation alone is sufficient to induce PTEN S-nitrosylation in the absence of PARK2 depletion. Park2 loss and Pten loss also display striking cooperativity to promote tumorigenesis in vivo. Together, our findings reveal an important missing mechanism that might account for PTEN suppression in PARK2-deficient tumors, and they highlight the importance of PTEN S-nitrosylation in supporting cell survival and proliferation under conditions of energy deprivation.

Biophysical and Biochemical Characterization of Structurally Diverse Small Molecule Hits for KRAS Inhibition.

We describe six compounds as early hits for the development of direct inhibitors of KRAS, an important anticancer drug target. We show that these compounds bind to KRAS with affinities in the low micromolar range and exert different effects on its interactions with binding partners. Some of the compounds exhibit selective binding to the activated form of KRAS and inhibit signal transduction through both the MAPK or the phosphatidylinositide 3-kinase PI3K-protein kinase B (AKT) pathway in cells expressing mutant KRAS. Most inhibit intrinsic and/or SOS-mediated KRAS activation while others inhibit RAS-effector interaction. We propose these compounds as starting points for the development of non-covalent allosteric KRAS inhibitors.

The Resurgence of Lymphogranuloma Venereum: Changing Presentation of Lymphogranuloma Venereum in the Era of HIV Preexposure Prophylaxis, 2004 to 2022.

BACKGROUND: Before the early 2000s, the sexually transmitted infection lymphogranuloma venereum (LGV) was rare in high-income countries. Initially, most cases in these countries were among symptomatic men who have sex with men (MSM) living with HIV. In the context of widespread HIV preexposure prophylaxis (PrEP), LGV's epidemiology may be changing. We aimed to characterize the epidemiology and clinical presentation of LGV in the PrEP era. METHODS: A retrospective chart review was performed on all LGV cases occurring between November 2004 to October 2022 in British Columbia (BC), Canada. Cases were stratified by having occurred before (2004-2017) or after widespread PrEP availability in BC (2018-2022). Annual rates and test positivity percentages were calculated. Bivariate logistic regression was performed to identify drivers of asymptomatic infection in the PrEP era. RESULTS: Among 545 cases identified, 205 (37.6%) occurred pre-PrEP and 340 (62.4%) occurred during the PrEP era. Most cases were among MSM (97.2%). The estimated rate of LGV has doubled from 2018 to 2022, reaching 1535.2 cases per 100,000 PrEP users. Most PrEP-era cases were among HIV-negative individuals (65.3%), particularly those on PrEP (72.6%). Cases in the PrEP era were often asymptomatic compared with pre-PrEP (38.6% vs. 19.3%; P < 0.001). Users of PrEP were more likely to experience asymptomatic infection compared with HIV-negative PrEP nonusers (odds ratio, 2.07; 95% confidence interval, 1.07-3.99). CONCLUSIONS: In the context of increased asymptomatic testing, LGV may be increasing in BC. Most infections now occur among HIV-negative MSM. A high proportion of infections are asymptomatic.

Simulation training in mammography with AI-generated images: a multireader study.

OBJECTIVES: The interpretation of mammograms requires many years of training and experience. Currently, training in mammography, like the rest of diagnostic radiology, is through institutional libraries, books, and experience accumulated over time. We explore whether artificial Intelligence (AI)-generated images can help in simulation education and result in measurable improvement in performance of residents in training. METHODS: We developed a generative adversarial network (GAN) that was capable of generating mammography images with varying characteristics, such as size and density, and created a tool with which a user could control these characteristics. The tool allowed the user (a radiology resident) to realistically insert cancers within different regions of the mammogram. We then provided this tool to residents in training. Residents were randomized into a practice group and a non-practice group, and the difference in performance before and after practice with such a tool (in comparison to no intervention in the non-practice group) was assessed. RESULTS: Fifty residents participated in the study, 27 underwent simulation training, and 23 did not. There was a significant improvement in the sensitivity (7.43 percent, significant at p-value = 0.03), negative predictive value (5.05 percent, significant at p-value = 0.008) and accuracy (6.49 percent, significant at p-value = 0.01) among residents in the detection of cancer on mammograms after simulation training. CONCLUSION: Our study shows the value of simulation training in diagnostic radiology and explores the potential of generative AI to enable such simulation training. CLINICAL RELEVANCE STATEMENT: Using generative artificial intelligence, simulation training modules can be developed that can help residents in training by providing them with a visual impression of a variety of different cases. KEY POINTS: Generative networks can produce diagnostic imaging with specific characteristics, potentially useful for training residents. Training with generating images improved residents' mammographic diagnostic abilities. Development of a game-like interface that exploits these networks can result in improvement in performance over a short training period.

Benefits of Rib Fixation Utilizing Low-Cost Materials: A Randomized Pilot Trial.

INTRODUCTION: Surgical stabilization of rib fractures (SSRF) using standard rib plating systems has become a norm in developed countries. However, the procedure has not garnered much interest in low-middle-income countries, primarily because of the cost. METHODS: This was a single-center pilot randomized trial. Patients with severe rib fractures were randomized into two groups: SSRF and nonoperative management. SSRF arm patients underwent surgical fixation in addition to the tenets of nonoperative management. Low-cost materials like stainless steel wires and braided polyester sutures were used for fracture fixation. The primary outcome was to assess the duration of hospital stay. RESULTS: Twenty-two patients were randomized, 11 in each arm. Per-protocol analysis showed that the SSRF arm had significantly reduced duration of hospital stay (22.6 ± 19.1 d versus 7.9 ± 5.7 d, P value 0.031), serial pain scores at 48 h and 5 d (median score 5, IQR (3-6) versus median score 7, IQR (6.5-8), P value 0.004 at 48 h and median score 2 IQR (2-3) versus median score 7 IQR (4.5-7) P value 0.0005 at 5 d), significantly reduced need for injectable opioids (9.9 ± 3.8 mg versus 4.4 ± 3.4 mg, P value 0.003) and significantly more ventilator-free days (19.9 ± 8.7 d versus 26.4 ± 3.2 d, P value 0.04). There were no statistically significant differences in the total duration of ICU stay (median number of days 2, IQR 1-4.5 versus median number of days 7, IQR 1-14, P value 0.958), need for tracheostomy (36.4% versus 0%, P value 0.155), and pulmonary and pleural complications. CONCLUSIONS: SSRF with low-cost materials may provide benefits similar to standard rib plating systems and can be used safely in resource-poor settings.

Synergistic effects of salt and ultraviolet radiation on the rice-field cyanobacterium Nostochopsis lobatus HKAR-21.

Environmental variation has a significant impact on how organisms, including cyanobacteria, respond physiologically and biochemically. Salinity and ultraviolet radiation (UVR)-induced variations in the photopigments of the rice-field cyanobacterium Nostochopsis lobatus HKAR-21 and its photosynthetic performance was studied. We observed that excessive energy dissipation after UVR is mostly caused by Non-Photochemical Quenching (NPQ), whereas photochemical quenching is important for preventing photoinhibition. These findings suggest that ROS production may play an important role in the UVR-induced injury. To reduce ROS-induced oxidative stress, Nostochopsis lobatus HKAR-21 induces the effective antioxidant systems, which includes different antioxidant compounds like carotenoids and enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). The study indicates that Nostochopsis lobatus HKAR-21 exposed to photosynthetically active radiation + UV-A + UV-B (PAB) and PAB + NaCl (PABN) had significantly reduced photosynthetic efficiency. Furthermore, maximum ROS was detected in PAB exposed cyanobacterial cells. The induction of lipid peroxidation (LPO) has been investigated to evaluate the impact of UVR on the cyanobacterial membrane in addition to enzymatic defensive systems. The maximal LPO level was found in PABN treated cells. Based on the findings of this research, it was concluded that salinity and UVR had collegial effects on the major macromolecular components of the rice-field cyanobacterium Nostochopsis lobatus HKAR-21.

Deployment of Artificial Intelligence in Radiology: Strategies for Success.

Radiology, as a highly technical and information-rich medical specialty, is well-suited for artificial intelligence (AI) product development, and many FDA-cleared AI medical devices are authorized for uses within the specialty. In this Clinical Perspective, we discuss the deployment of AI tools in radiology, exploring regulatory processes, the need for transparency, and other practical challenges. We further highlight the importance of rigorous validation, real-world testing, seamless workflow integration, and end-user education. We emphasize the role for continuous feedback and robust monitoring processes, to guide AI tools' adaptation and help ensure sustained performance. Traditional standalone and alternative platform-based approaches to radiology AI implementation are considered. The presented strategies will help achieve successful deployment and fully realize AI's potential benefits in radiology.

Pyrogallol-based dipodal optical probe as new smart analytical tool for sustainable detection of cobalt in biosystem.

The present research focuses on the micro-level detection of cobalt ions in biological and environmental samples using a new probe. The probe is a multifunctional symmetrical dipodal molecule with two pyrogallol binding units attached to the malonate scaffold through a propylene spacer. It was synthesized and characterized by 1H NMR, 13C NMR, IR, electronic spectroscopy, and mass spectrometry. The molecule's binding, thermodynamic, and photophysical properties are also described. The designed probe demonstrates an excellent sensing ability for Co(II) based on the ESIPT "OFF-ON" fluorescence mechanism. The experiments explore the high selectivity of the ligand for cobalt sensing over a wide range of metal ions of biological and environmental importance. The fluorescence intensity shows a linear response to Co(II) in 5-100 µM concentration with a detection limit of 8.75 x 10-5 and a 2.65-fold enhancement in the intensity. These results establish its potential application as a fluorescence sensor. The probe is also employed as a colorimetric sensor for the qualitative determination of cobalt ions in DMSO solution. The interesting behavior of the probe motivated us further to study its coordination properties with divalent cobalt in solution. The pre-organized assembly with an appropriate cavity size favors the ligand for an efficient Co(II) encapsulation by coordinating through imine-Ns and aromatic ring-Os donors, giving high formation constants.

Minimum information for reporting on the TEER (trans-epithelial/endothelial electrical resistance) assay (MIRTA).

Standard information reporting helps to ensure that assay conditions and data are consistently reported and to facilitate inter-laboratory comparisons. Here, we present recommendations on minimum information for reporting on the TEER (trans-epithelial/endothelial electrical resistance) assay (MIRTA). The TEER assay is extensively used to evaluate the health of an epithelial/endothelial cell culture model and as an indicator of the potential toxicity of a test substance. This publication is the result of an international collaboration─called the RespTox (Respiratory Toxicity) Collaborative─through which twelve laboratories shared their protocols for assessing the barrier function of respiratory epithelial cells using the TEER assay following exposure to substances. The protocols from each laboratory were reviewed to identify general steps for performing the TEER assay, interlaboratory differences between steps, the rationale for differences, whether these differences impact results or cross-laboratory comparisons between TEER measurements. While the MIRTA recommendations are focused on respiratory epithelial cell systems, these recommendations can be adapted for other cell systems that form barriers. The use of these recommendations will support data transparency and reproducibility, reduce challenges in data interpretation, enable cross-laboratory comparisons, help assess study quality, and facilitate the incorporation of the TEER assay into national and international testing guidance.

Pre-pregnancy planning for female patients seen at a pregnancy and rheumatic diseases clinic: a retrospective analysis of patients with rheumatic diseases seeking pregnancy-related care.

To assess the clinical utility of pre-pregnancy planning among female patients with rheumatic diseases attending a targeted pregnancy and rheumatic diseases clinic. We conducted a retrospective review using data collected via chart review of female patients with rheumatic diseases seen at the Pregnancy and Rheumatic Diseases Clinic at the Mary Pack Arthritis Centre in Vancouver, Canada, between January 2017 and July 2020. Patients were categorized according to an initial presentation at the clinic as (1) pregnant without pre-pregnancy planning; and (2) not pregnant with pre-pregnancy planning. The latter group was further categorized according to whether they had contraindications to pregnancy. Pregnancy outcomes were extracted from electronic medical records and analyzed using descriptive statistics. Our study included 230 female patients with rheumatic diseases. At the initial clinical presentation, 86 were pregnant and 144 were planning to become pregnant and presenting for pre-pregnancy planning. Compared to patients without pre-pregnancy planning, patients who received pregnancy planning experienced fewer prenatal disease flares (61.3% [38/62] vs. 22.6% [7/31]; p < 0.001), fewer medication changes during pregnancy (46.4% [39/84] vs. 18.9% [10/53]; p = 0.002), and improved disease control in the first trimester of pregnancy (p = 0.018). There were no statistically significant differences in the frequency of adverse pregnancy or fetal outcomes between patients with and without pre-pregnancy planning. Evaluation of patient outcomes suggests that pre-pregnancy planning may support early assessment of high-risk pregnancy status; therein, allowing healthcare providers to identify and manage risk factors for adverse pregnancy outcomes among patients living with rheumatic diseases.

Frequency of self-reported persistent post-treatment genital hypoesthesia among past antidepressant users: a cross-sectional survey of sexual and gender minority youth in Canada and the US.

PURPOSE: Persistent post-treatment genital hypoesthesia (PPTGH) is a primary symptom of post-SSRI sexual dysfunction (PSSD), an iatrogenic syndrome characterized by enduring sexual dysfunction following the discontinuation of some antidepressants. We aimed to estimate the frequency of PPTGH among past users of psychiatric treatments, particularly antidepressants. METHODS: We used a subsample of UnACoRN, a US/Canada survey of sexual and gender minority youth aged 15 to 29. We included participants with a history of psychiatric drug use. We excluded individuals with genital surgeries or without sexual experience. The analysis involved chi-square tests for initial group comparisons, post hoc tests for multiple comparisons, and logistic regression among those who had stopped taking medication. We exponentiated the regression to estimate the odds of PPTGH by drug type, adjusting for age, sex-assigned-at-birth, hormone treatment, and depression severity in three nested models. RESULTS: 574 of 2179 survey participants reported genital hypoesthesia. They were older and more likely to report male sex assignment at birth, hormonal therapy history, and psychiatric drug history. The frequency of PPTGH among antidepressant users was 13.2% (93/707) compared to 0.9% (1/102) among users of other medications; adjusted odds ratio: 14.2 (95% CI: 2.92 to 257). CONCLUSION: Antidepressant discontinuation is strongly associated with PPTGH in the US and Canada where SSRI/SNRI medications account for 80% of antidepressant prescriptions. We call for standardized international warnings and transparent, informed consent. Future research should expand upon our efforts to estimate the risk of PSSD by including all the proposed diagnostic criteria, including documentation of temporal changes in PSSD-related symptoms before and after treatment (≥3 months).

This study explored the long-lasting sexual side effects­specifically, reduced genital sensitivity­of certain antidepressants, even after stopping the medication, in a diverse group of young people, primarily those identifying as sexual and gender minorities. We analyzed responses from a large survey, focusing on participants with a history of psychiatric drug use but without genital surgeries. Our findings indicate that those who used antidepressants experienced a substantial increase in reports of reduced genital sensitivity­13.2% of antidepressant users compared to 0.9% of users of other medications. This symptom is more common among individuals who had used antidepressants and sedatives. Our results emphasize the necessity for clear warnings and proper consent processes about potential long-term sexual side effects, particularly for young patients, and standardization of these procedures across countries. Further research is needed to explore this condition more deeply, including studies of all related symptoms and their development over time before and after treatment.

May Measurement Month 2021: an analysis of blood pressure screening campaign results from India.

Raised blood pressure (BP) is the leading preventable risk factor for cardiovascular diseases that makes a major impact on early mortality and morbidity. Recognizing hypertension in the community, educating people about routine BP monitoring, and improving medication compliance are all important steps in detecting, controlling, and managing hypertension. During the course of 5 months, members of the Indian Society of Hypertension organized unique medical indoor and outdoor camps at 100 screening locations around India for the May Measurement Month (MMM) 2021 study. At every location, BP was measured three times, and a questionnaire was completed. Participants known to have hypertension before the study whether taking or not taking treatment were not included (not a normal pre-requisite for exclusion in MMM). The analysis included 15 045 participants in total. After calculating the average of the second and third BP measurements, 16.4% of participants were found to have hypertension based on ≥140/90 mmHg thresholds (2461 out of 15 045). 14.0% of females and 16.4% of males had hypertension. 16.4% of participants had undiagnosed hypertension and were not receiving treatment. The MMM screening campaign has the potential for identifying large numbers of people with undiagnosed hypertension and raising awareness of the importance of raised BP among the general public, medical professionals, policymakers, the government, and the media. Future BP screening campaigns should be larger in scope and involve follow-ups with past participants.

Preoperative topical estrogen application in the management of hypospadias: a systematic review.

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18 years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies.Registration and protocol: Registered in Prospero CRD42024502183.

Risk factors and outcome of antenatally diagnosed congenital diaphragmatic hernia following in-utero transfer in a busy public-sector tertiary care center in North India.

We analyzed the risk factors and outcomes of antenatally diagnosed congenital diaphragmatic hernia (CDH) from a tertiary-care children's hospital following in-utero transfer. A total of 41 antenatally detected cases of CDH were included; 30 were live-born and 11 were still-born. The primary outcome was postnatal survival. The secondary outcome was the probable factor affecting survival. No medical termination of the pregnancy was done. The mean gestational age at diagnosis was 23 weeks. The diagnostic accuracy of antenatal ultrasonography was 40/41 (97.5%). Lung-to-head ratio (LHR) was <1 in 20 cases (survived 2), LHR was >1 in 10 cases (survived 8), and LHR was not recorded in 11 cases (survived 4). Overall survival was 14/41 (34.1%). Survival in fetuses with polyhydramnios was 0% (n=3; survived 0), associated anomalies were 33.3% (n=3; survived 1), and liver herniation was 22.2% (n=9; survived 2). Postnatally, significant risk factors included a low Apgar score, the need for ventilation, and neonatal intensive care unit (NICU) management. Survival in live-born cases was 14/30 (46.6%) and in operated cases was 14/19 (73.6%). We concluded that antenatal ultrasound had a high accuracy rate for detecting CDH. Antenatal risk factors affecting outcomes were low LHR, maternal polyhydramnios, liver herniation, and associated malformations. Postnatal risk factors included a low Apgar score, NICU admission, and a need for ventilation. The overall survival rate, as well as the survival rates for live-borns and those undergoing surgery, were 34.1%, 46.6%, and 73.6%, respectively. This data will guide clinicians in counseling the families of antenatally diagnosed CDH.

Fortifying Micronutrient Supplementation in India: Indian Expert consensus.

Micronutrients play a key role in human health, being involved in energy metabolism, immunity, cellular functioning, growth, and development. Deficiencies in micronutrients occur in individuals of all ages due to several factors, including inadequate diets, disease states, and overweight/obesity. Guidelines from the Indian Council of Medical Research (ICMR) National Institute of Nutrition (NIN) Expert Group on Nutrient Requirements for Indians (2023) have specified the Recommended Dietary Allowances (RDA) for macronutrients and micronutrients. In addition, a healthy diet is crucial for overall health and should be the first step toward addressing micronutrient deficiencies. When diet is inadequate, micronutrient supplements can be provided to compensate. An expert panel of Indian doctors was convened to develop a pathway toward micronutrient supplementation among the Indian population. This Consensus Statement recognizes that different populations have varying needs for specific micronutrients, and ensuring adequate intake of such micronutrients can improve health outcomes. The panel provided recommendations for dietary practices and micronutrient supplementation when diet is inadequate. Addressing micronutrient deficiencies at the primary care level can prevent chronic deficiencies and their consequences. This Consensus Statement can serve as a primer for physicians to monitor and address deficiencies and thus help individuals maintain their health.

Responsible Use of Oral Corticosteroids in People with Comorbid Diabetes: An Expert Consensus.

Globally, diabetes mellitus (DM) is a substantial contributor to morbidity and mortality. Comorbidities and intercurrent illnesses in people with diabetes may necessitate the use of steroids. Acute as well as chronic use of steroids contributes substantially to the development of various complications. Despite this, there are no standard guidelines or consensus to provide a unified approach for the rational use of steroids in people with diabetes. Also, there is scant harmonization among clinicians with the use of different steroids in routine practice. To address the inconsistencies in this clinical arena, the consensus working group (CWG) formulated a unified consensus for steroid use in people with diabetes. In people with diabetes, the use of steroids causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA). An increase in weight is directly related to the dose and duration of the steroid therapy. Steroid-related alterations in hyperglycemia, dyslipidemia, and hypertension (HTN) add to the increased risk of cardiovascular (CV) disease. The risk of complications such as infections, osteoporosis, myopathy, acne, cataracts, and glaucoma may increase with the use of steroids. Appropriate and timely monitoring of these complications is necessary for early detection and treatment of such complications. Given the systemic effects of various antihyperglycemic drugs, there is a possibility of aggravating or diminishing the specific complications. Preference to a safer steroid is required matching the steroid dose equivalence and individualizing patient management. In conclusion, short-, intermediate-, or long-term use of steroids in people with diabetes demands their rational use and holistic approach to identify, monitor, and treat the complications induced or aggravated by the steroids.

Perinatal Use and Discontinuation of Disease-Modifying Antirheumatic Drugs: Outcomes of Patients Seen at a Pregnancy and Rheumatic Diseases Clinic.

BACKGROUND: Managing rheumatic disease activity using pregnancy-compatible medications is essential for reducing adverse maternal and fetal outcomes. We characterized medication use and discontinuation before, during, and after pregnancy, among female patients with rheumatic diseases attending a targeted pregnancy and rheumatic diseases clinic. METHODS: We conducted a cross-sectional medical record review of female patients with rheumatic diseases at a Canadian clinic between January 2017 and July 2020. Patients were categorized by pregnancy stage at their latest clinic visit: (1) preconception; (2) pregnant; (3) postpartum. We assessed use of conventional, biologic, and targeted synthetic disease-modifying antirheumatic drugs (DMARDs), prednisone, and nonsteroidal anti-inflammatory drugs across 6 perinatal windows: 24 and 12 months preconception, each pregnancy trimester, and 3 months postpartum. We reported adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for medication discontinuation in the first trimester and subsequent disease flare. RESULTS: Of 230 included patients, 85 (37.0%), 12 (5.2%), and 133 (57.8%) were preconception, pregnant, and postpartum, respectively. Approximately half experienced at least 1 disease flare during each pregnancy stage (56.4% preconception, 58.1% during pregnancy, and 53.7% postpartum). Most used at least 1 DMARD throughout the perinatal period (82.6% preconception, 55.6% during pregnancy, and 45.1% postpartum). Overall, 25.5% discontinued at least 1 DMARD in the first trimester. DMARD discontinuation was associated with disease flare during pregnancy (aOR, 1.49; 95% CI, 0.55-4.03; p = 0.87) and postpartum (aOR, 3.09; 95% CI, 0.83-11.47; p = 0.09). CONCLUSIONS: Patients receiving care at a pregnancy and rheumatic disease clinic show perinatal medication use patterns consistent with recent recommendations and clinical guidelines.

Adjuvant therapy may improve overall survival in high-risk periampullary adenocarcinomas patients - A match-pair analysis from a multi-institutional cohort study (The MIPPAP study).

BACKGROUND: The role of adjuvant therapy in resected periampullary adenocarcinomas is equivocal due to contrasting data and limited prospective trials. METHODS: The Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP), included data from 8 institutions across India. Of the 1679 pancreatic resections, 736 patients with T3/T4 and/or Node positive adenocarcinomas (considered as high risk for recurrence) were included for analysis. Three (adjuvant): one (observation) matching, using T3/T4 T staging, nodal positivity and ampullary subtype was performed by using the nearest neighbour matching method. RESULTS: Of 736 patients eligible for inclusion, 621 patients were matched of which 458 patients received adjuvant therapy (AT) (predominantly gemcitabine-based) and 163 patients were observed (O). With a median follow-up of 42 months, there was a statistical difference in overall survival in favour of patients receiving AT as compared to those on observation [68.7 months vs. 61.1 months, Hazard ratio: 0.73 (95% CI: 0.54-0.97); p = 0.03]. Besides AT, presence of nodal involvement (median OS: 65.4 months vs not reached; p = 0.04) predicted for inferior OS. CONCLUSIONS: The results of the match-pair analysis suggest that adjuvant therapy improves overall survival in periampullary adenocarcinomas at high risk of recurrence with a greater benefit in T3/T4, node-positive and ampullary subtypes.

A Case Report on Hendren's Technique for Managing Symptomatic Isolated Urogenital Sinus in an Infant.

Isolated urogenital sinus is a rare anomaly. These cases may have high confluence which adds complexity to surgical correction. There are controversies regarding timing and techniques of management. We present a case report on managing such a case in an infant with bladder outlet obstruction and pyocolpos.