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Interstitial ectopic pregnancy is a rare but life-threatening condition, accounting for 2.4 % of all ectopic pregnancies. Diagnosing it can be challenging, as the interstitial portion of the fallopian tube allows for delayed rupture due to its capacity to expand, often leading to significant haemorrhage. Early detection is critical to preventing severe complications. We report the case of a 30-year-old primigravida who presented for routine antenatal care at 12 weeks of gestation, asymptomatic with no identifiable risk factors. Routine ultrasound revealed a suspicious gestation near the left uterine horn, leading to a diagnosis of interstitial ectopic pregnancy via MRI. The patient underwent a laparotomy with successful wedge resection and salpingectomy. She recovered well without complications. This case highlights the diagnostic challenges of interstitial ectopic pregnancy, which can remain asymptomatic longer than other types due to the anatomical features of the interstitial segment. Diagnostic imaging is vital for accurate diagnosis, especially in stable patients. Early intervention is key to avoiding catastrophic outcomes like uterine rupture and severe haemorrhage. Advances in imaging and surgical techniques have improved patient outcomes, but careful prenatal follow-up remains crucial for future pregnancies due to the increased risk of uterine rupture. Routine antenatal care and imaging play a pivotal role in the early detection of interstitial ectopic pregnancies. Prompt diagnosis and management can significantly reduce the risk of severe complications, emphasizing the importance of vigilant prenatal monitoring in reducing maternal morbidity and mortality. • Rare finding of interstitial ectopic pregnancy • Diagnosis on routine antenatal screening • Asymptomatic until catastrophic • Importance of components of antenatal screening [ABSTRACT FROM AUTHOR]

While long-term immunosuppression has drastically improved heart transplant (HT) viability, resultant side effects might contribute to morbidity and mortality. Discontinuation of corticosteroids might be feasible without adversely affecting outcomes. We compared outcomes in adult HT recipients with or without steroids 1-year post-transplant in a large, international registry. We reviewed adults (age ≥ 18 years) who underwent their first heart-only transplantation between January 2010 and June 2018 in the ISHLT database with follow-up through April 2019 who were discharged from the hospital on steroids. We divided the cohort into those with or without steroids by their 1-year follow-up. Those who died or who lacked information on steroid use by 1 year were excluded. We compared the risk-adjusted 2-, 3-, and 5-year survival as well as the development of coronary allograft vasculopathy (CAV), treated rejection within 2-years, diabetes, malignancy, and severe renal dysfunction after transplant. We identified 17,483 HT recipients, 8,750 (50.0%) of whom stopped steroids 1-year post-HT. Those who were receiving steroids were significantly younger, more likely female, had a higher BMI, higher IABP and LVAD use before HT, worse renal function, and slightly longer ischemic time. Survival rates (conditional on 1-year survival) significantly differed between the steroid and non-steroid groups at 2-years (96.2% vs. 98.0%, p<0.001), 3-years (93.3% vs. 96.5% p<0.001), and 5-years (89.8% vs. 94.0%, p<0.001)(Figure). After adjusting for factors such as recipient age, BMI, history of diabetes, and HF etiology among others, continuation of steroids was associated with a significantly higher risk of 2-year (HR 1.92, 95% CI 1.60-2.31), 3-year (HR 1.88, 95% CI 1.63-2.16), and 5-year mortality (HR 1.64, 95% CI 1.47-1.82). Furthermore, continuing steroid was also associated with significantly a higher odds of CAV (OR 1.09, 95% CI 1.01-1.18), diabetes (OR 1.23, 95% CI 1.12-1.36), 2-year treated rejection (OR 2.50, 95% CI 2.25-2.73), and severe renal dysfunction (OR 1.66, 95% CI 1.50-1.84) with no difference in malignancy rates (OR 0.85, 95% CI 0.70-1.04). Continuation of corticosteroid 1-year after heart transplant was associated with significantly lower survival and greater adverse outcomes among the heart transplant recipients enrolled in the ISHLT registry. [ABSTRACT FROM AUTHOR]

Long term continuous intravenous inotrope infusion therapy (LTInT) has improved the quality of life for patients with refractory heart failure with reduced ejection fraction. However, its utility in symptomatic, refractory heart failure with preserved ejection fraction >40% (HFpEF) remains less well-described. We describe the characteristics and outcomes of such patients at our center. We conducted a retrospective review of consecutively enrolled patients with HFpEF who received LTInT from 2016-2022, for 19378 cumulative person-days of follow-up (∼646 person-months). Of the 65 participants (mean age 74±11 years), 23 were female and 42 were male. Dobutamine was used for 23 participants whereas 42 received milrinone. LTInT was used palliatively for 46 patients. A total of 150 hospitalizations occurred in the pre-inotrope year, with a median (quartile 1-3) of 2(1-4) hospitalizations per patient per year. While receiving LTInT, fewer cardiovascular hospitalizations were observed, totaling 96 hospitalizations with a median of 1(0-4) hospitalizations per patient per year, p=0.005. All-cause hospitalizations were numerically lower but the difference was not statistically significant (median 1[0-4], p=0.3, Total=142). 25 deaths (38%) occurred in the cohort. On an average, deaths occurred 7 months after initiating LTInT. Dobutamine recipients had a higher mortality rate than milrinone recipients (65% vs 24%, p=0.001) (Table). However, this was confounded by the observation that patients on dobutamine had a significantly worse NYHA class functional statuses and had higher N-terminal-pro-Brain Natriuretic Peptide (BNP) levels. Long term intravenous inotrope infusion therapy has the potential to reduce cardiovascular hospitalizations in patients with HFpEF. Given that heart failure is a progressive disease, the absence of an increase in the number of all-cause hospitalizations over a prolonged follow-up period is encouraging. [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure especially in patients with preserved ejection fraction. Care in a dedicated center involving a multidisciplinary team improves the management and outcomes in CA. Such centers are still scarce, and access to patient care is still limited. To promote awareness of the disease, and help standardize the care of these complex patients while keeping care local we established a cardiac amyloidosis management program (CAMP) in early 2019. We describe our 5-year experience with the program. Our CAMP was established in March 2019 in a tertiary care university affiliate teaching hospital system. Herein, we review the growth in awareness, referral patterns, and clinical outcomes from March 2019 to March 2024. We formed a multidisciplinary team including members from heart failure, imaging, hematology/oncology, neurology, and pathology. Since the inception of our CAMP, 320 patients have been referred for evaluation. A confirmed diagnosis of CA was made for 214 individuals (170 male) - 196 with ATTR CA, 15 with AL CA, 1 with AApoA-IV CA. The average age of the cohort with confirmed CA was 82.1 ± 9 years. Of the patients with TTR amyloid, 19 had hereditary ATTR. The most commonly identified pathological mutation was pV142I in 13 patients. Other identified mutations were p.Ala140Ser, p.V122I, pV30M mutation, pThr60Ala. Trends in referrals and diagnosis are described in the Illustration. We observed a slight decrease in referral rates below the projected trajectory in the months immediately following the COVID-19 pandemic, with a subsequent recovery (Illustration). The cumulative duration of follow-up was 266 patient years. A total of 1721 all-cause hospitalizations occurred during the duration of follow-up, averaging 6.5 admissions per person-year. The rates of all-cause hospitalizations were numerically higher for AL vs ATTR CA, but the difference was not statistically significant (median 18 vs 4, p=0.1). A total of 44 deaths occurred. Patients with ATTR CA had a significantly lower mortality than patients with AL CA (18% vs 53%, p=0.003). The growth of our dedicated CA program above predicted trends supports successful awareness about CA and the creation of a growing partnership in providing care with other providers in our community. [ABSTRACT FROM AUTHOR]

In controlled studies, Mavacamten improved exercise capacity with minimal adverse effects in patients with symptomatic hypertrophic cardiomyopathy with obstruction (HOCM). We describe our experience from a cohort of adults treated with mavacamten in a hypertrophic cardiomyopathy center in the United States. We reviewed 26 consecutive adult patients with HOCM and peak left ventricular outflow gradients (LVOT) of ≥ 50 mmHg. We compared baseline characteristics and echocardiographic parameters, including ejection fraction (EF) and LVOT gradients at rest and during Valsalva. LVOT gradients at baseline and 4, 8, and 12 weeks were compared using Friedman's test, and EFs were compared using repeated measures ANOVA in similar timeframes. The mean age was 61.8 years; 53% were female, 88% were white, 61% were obese (average BMI 32 kg/m2), and 77% had hypertension. MYPBC3 and MYH7 pathogenic variants were identified in four and one patient, respectively. Most (84%) were treated with metoprolol succinate with an average dose of 79 mg, and 7% with calcium channel blockers before mavacamten. The starting dose of mavacamten per protocol was 5 mg daily. Compared to the baseline median LVOT gradient measured at rest and during Valsalva, there was a statistically significant reduction of 35.6 mmHg and 43 mmHg at four weeks, 30.8 mmHg and 37.2 mmHg at eight weeks and 27 mmHg and 32.2 mmHg at 12 weeks, respectively (p rest =0.00001, p valsalva =0.0001). Of note, 13 patients required dose reduction due to rapid decline in the LVOT gradients as per protocol, and two out of those 13 required temporary discontinuation due to persistence of the low LVOT gradients. One patient had persistently high gradients despite being maintained on a max dose of 15 mg daily. Compared to the baseline, there was a significant decrease in mean LVEF by 5.34% at four weeks, 5.45% at eight weeks, and 2.84% at 12 weeks (p=0.0002). No patients experienced significant adverse effects, including a reduction in EF to less than 50%, symptomatic heart failure, arrhythmia, syncope, or death. Twenty patients reported improvement in NYHA class by ≥1 class. Our clinical experience shows that treatment with mavacamten was highly effective at reducing LVOT gradients and alleviating symptoms without increased adverse effects. [ABSTRACT FROM AUTHOR]

The discharge loop diuretic regimen following the first hospitalization for decompensated heart failure (DHF) is unknown. We investigated the discharge loop diuretic prescription relative to admission dose following the first hospitalization for DHF in a large multi-hospital healthcare system in the United States. We reviewed 5,185 consecutive patients hospitalized with the first DHF who were discharged alive from January 2018 through May 2021. The study cohort was divided into 4 groups as per the relation between discharge and admission loop diuretic dosing: discharge greater than admission diuretic dose (Group 1), discharge equivalent to admission diuretic dose (Group 2), discharge less than admission diuretic dose (Group 3), and discharge with no diuretic (Group 4). For patients who were admitted on a different loop diuretic than the one they were prescribed at discharge, the following oral dose equivalents were used: 1 mg bumetanide = 20 mg torsemide = 40 mg furosemide. We identified 5,185 patients during the study period who were hospitalized with the first DHF. The study cohort had a mean age of 75.1±13.5 years, body mass index of 31.29±9.75 kg/m2, glomerular flow rate (GFR) of 47.39±23.63 ml/minute and 50.84±23.57 mL/minute at the time of admission and discharge, respectively, and included 50.4% who were female, 75.6% who were white, 80.6% who were admitted from home, and 60% who had a preserved left ventricular ejection fraction. A majority (71.4%) of these patients were discharged either with no (69.2%) or lower than admission (2.2%) loop diuretic regimen. Group 1 patients had significantly higher last hemoglobin level than group 4 (P=.002; 95% CI=0.14-0.86) and group 2 (P=.045, 95% CI=0.00-0.76). Group 1 had significantly lower first serum creatinine (p=.016, 95% CI=.03-0.49) and higher first GFR (p<.001; 95% CI = 2.19-10.59) than those in group 4. Group 1 also had higher first GFR than group 3 (p=.039; 95% CI = 0.23-14.40). Similarly group 2 had higher first GFR than group 4 (P=.003, 95% CI=0.63-4.73) (Table). The majority (71.4%) of patients were discharged either with no (69.2%) or lower than admission (2.2%) loop diuretic dose. Older patients with a lower GFR and patients with anemia were significantly less likely to be discharged on loop diuretics after the first hospitalization of decompensated heart failure. [ABSTRACT FROM AUTHOR]

Orthotropic heart transplantation (OHT) remains the gold standard for end-stage heart failure, with left ventricular assist devices (LVAD) being offered as a bridge to transplant or as destination therapy when OHT cannot be performed. Advancements in LVAD technology and evolving organ allocation policies have shifted the dynamics between LVAD and OHT usage. This study leverages a nationwide database to compare index admission complications between OHT and LVAD recipients, providing critical insights into their real-world clinical implications. Our study population was derived from the 2018-2020 Nationwide Readmissions Database (NRD) from the Healthcare Cost and Utilization Project of the United States Agency for Healthcare Research and Quality. In our retrospective analysis, we examined data spanning from January 2018 to December 2020, focusing on individuals aged 18 years and older who were identified as recipients of OHT or newer generation centrifugal LVAD implantation. During the study, 4989 (48.66%) patients received OHT and 5263 (51.34%) received LVAD. In the comparative analysis we observed that, OHT patients had a lower risk of dysrhythmias (aOR: 0.66; CI: 0.57-0.76; p<0.001), acute myocardial infarction (AMI) (aOR: 0.41; CI: 0.20-0.85; p=0.01), respiratory failure (aOR: 0.78; CI: 0.66-0.93; p<0.001), electrolyte disorders (aOR: 0.84; CI: 0.73-0.95; p<0.001), valve disorders (aOR: 0.61; CI: 0.50-0.75; p<0.001), hepatic failure (aOR: 0.55; CI: 0.43-0.70; p<0.001), and severe sepsis (aOR: 0.67; CI: 0.53-0.85; p<0.001), compared to LVAD patients. However, patients undergoing OHT had an increased risk of acute renal failure (aOR: 1.22; CI: 1.04-1.43; p=0.012) and pericarditis (aOR: 1.61; CI: 1.37-1.89; p<0.001). OHT patients were found to have a higher likelihood of post-procedural surgical complications (aOR: 1.44; CI: 1.11-1.88; p<0.001). Gastrointestinal bleeding presented a similar risk for both groups (aOR: 0.67; CI: 0.45-1.00; p=0.05) (Figure 1). Despite technological advancement, LVAD still carries higher complication risks during the initial hospital stay compared to OHT. [ABSTRACT FROM AUTHOR]

Patients with symptomatic cardiac amyloidosis (CA) have limited therapeutic options with many being ineligible for left ventricular assist devices or heart transplants. Tafamidis has limited efficacy in reversing advanced refractory CA. While long term continuous intravenous inotrope infusion therapy (LTInoT) might improve quality of life in individuals with advanced heart failure, its utility in symptomatic, refractory heart failure due to cardiac amyloidosis remains unknown. We describe our experience with LTInoT in patients with cardiac amyloidosis and refractory heart failure. We conducted a retrospective review of consecutively enrolled patients with cardiac amyloidosis on LTInoT from 2019-2023, cumulatively for 9031 person-days of follow-up (∼301 person-months). 17 patients (12 male) were included. Participants were predominantly White (n=11) with a mean age of 79±8 years. 10 participants had HFrEF and 13 had ATTR. Chronic kidney disease, hyperlipidemia, and atrial fibrillation were comorbid in 13(76%), 12(71%), and 12(71%) patients, respectively. The mean left ventricular EF was 32±14%. LTInoT comprised milrinone (n=10) and dobutamine (n=7). Concurrent medications included a mineralocorticoid receptor antagonist (n=11, 65%), Tafamidis (n=9, 53%), and sodium-glucose co-transporter inhibitor (n=7, 41%). Cardiovascular hospitalizations (Median [quartile 1-3]) decreased while receiving LTInoT relative to a year prior (2[1-3] vs 3[2-4], p=0.03). All-cause hospitalizations were similar (3[2-4]). 6 (35%) patients died within a year of LInoT (Table). The median duration after which mortality occurred was 6 months (Q1-Q3: 3-16 months). LTInoT has potential to reduce cardiovascular hospitalizations in advanced heart failure due to cardiac amyloidosis. Further investigation is needed to identify suitable candidates for LInoT. [ABSTRACT FROM AUTHOR]

The widespread use of the pesticide fipronil in domestic and agriculture sectors has resulted in its accumulation across the environment. Its use to assure food security has inadvertently affected soil microbiome composition, fertility and, ultimately, human health. Degradation of residual fipronil present in the environment using specific microbial species is a promising strategy for its removal. The present study delves into the omics approach for fipronil biodegradation using the native bacterium Rhodococcus sp. FIP_B3. It has been observed that within 40 days, nearly 84% of the insecticide gets degraded. The biodegradation follows a pseudo-first-order kinetics (k = 0.0197/d with a half-life of ∼11 days). Whole genome analysis revealed Cytochrome P450 monooxygenase, peroxidase-related enzyme, haloalkane dehalogenase, 2-nitropropane dioxygenase, and aconitate hydratase are involved in the degradation process. Fipronil-sulfone, 5-amino-1-(2-chloro-4-(trifluoromethyl)phenyl)-4- ((trifluoromethyl)sulfonyl)-1H-pyrazole-3-carbonitrile, (E)-5-chloro-2-oxo-3- (trifluoromethyl)pent-4-enoic acid, 4,4,4-trifluoro-2-oxobutanoic acid, and 3,3,3- trifluoropropanoic acid were identified as the major metabolites that support the bacterial degradation of fipronil. In-silico molecular docking and molecular dynamic simulation-based analyses of degradation pathway intermediates with their respective enzymes have indicated stable interactions with significant binding energies (−5.9 to −9.7 kcal/mol). These results have provided the mechanistic cause of the elevated potential of Rhodococcus sp. FIP_B3 for fipronil degradation and will be advantageous in framing appropriate strategies for the bioremediation of fipronil-contaminated environment. [Display omitted] • Rhodococcus sp. FIP_B3 is an efficient bio-degrader of fipronil. • Microcosm study reported ∼84 % degradation with pseudo-first-order kinetics. • Peroxidase enzyme potentially mediates fipronil to fipronil sulfone degradation. • Proteome analysis evidenced differential expression of fipronil degradative enzymes. • Metabolome analysis detected intermediary products validating the proposed pathway. [ABSTRACT FROM AUTHOR]

Plant diseases constantly threaten crops and food systems, while global connectivity further increases the risks of spreading existing and exotic pathogens. Here, we first explore how an integrative approach involving plant pathway knowledgegraphs, differential gene expression data, and biochemical data informing Raman spectroscopy could be used to detect plant pathways responding to pathogen attacks. The Plant Reactome (https://plantreactome.gramene.org) demonstrates the potential to synthesize knowledgegraphs depicting plant-pathogen interactions, leveraging availability of publicly available OMIC data sets related to major diseases of rice and maize. Plant pathway signatures may then guide the development of drone and satellite remote-sensing methods for early monitoring of disease outbreaks across farms and landscapes. A review of current proximal- and remote-sensing technology demonstrates the potential for actionable early pathogen detection. We furthermore identify knowledge gaps that need to be addressed for developing these tools as components of effective strategies for safeguarding global food security against current and emerging pathogens., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All Authors reports financial support was provided by Defense Advanced Research Projects Agency. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Reliable and recent data of human rabies deaths and animal bites are not available in India, where a third of global cases occur. Since there is a global target of eliminating dog-mediated human rabies by 2030, understanding whether the country is on track is essential. We aimed to estimate the animal-bite burden and the number of human rabies deaths in India., Methods: We conducted a community-based nationwide cross-sectional survey with a multistage cluster-sampling design from March 2, 2022 to Aug 26, 2023, covering 60 districts in 15 Indian states. The head of the household or an adult family member was interviewed to collect information about animal-bite history in family members, receipt of anti-rabies vaccination (ARV), and death following animal bite in the family. Annual animal-bite incidence along with 95% CIs were estimated after applying the sampling weights and adjusting for clustering. We estimated annual human rabies deaths using a decision-tree probability model with parameters from the community survey and laboratory data on rabies positivity among suspected rabid dogs., Findings: Of the 337 808 individuals residing in the 78 807 households surveyed, 2052 gave a history of animal bite, mostly (1576 [76·8%]) due to dogs in the past 1 year. The weighted and adjusted annual incidence of animal bite was 6·6 (95% CI 5·7-7·6) per 1000 population, translating into 9·1 million bites nationally. Annual dog-bite incidence was 5·6 (4·8-6·6) per 1000. Among people who had been bitten by a dog, 323 (20·5%) did not receive ARV, and 1043 (66·2%) received at least three doses. Nearly half (615 [49·1%]) of the 1253 individuals who received one dose did not complete their full course of vaccination. We estimated 5726 (95% uncertainty interval 3967-7350) human rabies deaths occurring annually in India., Interpretation: Although there was a substantial decline in human rabies deaths over the past two decades, to eliminate dog-mediated human rabies by 2030, India needs to fast-track its actions by adopting a focused one-health approach. Integrating human and animal surveillance, ensuring timely administration of full course of post-exposure prophylaxis, and accelerating dog vaccination across the country are crucial steps towards this goal., Funding: Indian Council of Medical Research., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)