A Machine Learning Model to Predict Risk for Hepatocellular Carcinoma in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background and Aims: Hepatocellular carcinoma (HCC) incidence is increasing and correlated with metabolic dysfunction-associated steatotic liver disease (MASLD; formerly nonalcoholic fatty liver disease), even in patients without advanced liver fibrosis who are more likely to be diagnosed with advanced disease stages and shorter survival time, and less likely to receive a liver transplant. Machine learning (ML) tools can characterize large datasets and help develop predictive models that can calculate individual HCC risk and guide selective screening and risk mitigation strategies. Methods: Tableau and KNIME Analytics were used for descriptive analytics and ML tasks. ML models were developed using standard laboratory and clinical parameters. Sci-kit learn algorithms were used for model development. Data from University of California (UC), Davis, were used to develop and train a pilot predictive model, which was subsequently validated in an independent dataset from UC San Francisco. MASLD and HCC patients were identified by International Classification of Diseases-9/10 codes. Results: Of the patients diagnosed with MASLD (n = 1561 training; n = 686 validation), HCC developed in 14% (n = 227) of the UC Davis training cohort and 25% (n = 176) of the UC San Francisco validation cohort. Liver fibrosis determined by the noninvasive Fibrosis-4 score was the strongest single predictor for HCC in the model. Using the validation cohort, the model predicted HCC development at 92.06% accuracy with an area under the curve of 0.97, F1-score of 0.84, 98.34% specificity, and 74.41% sensitivity. Conclusion: ML models can aid physicians in providing early HCC risk assessment in patients with MASLD. Further validation will translate to cost-effective, personalized care of at-risk patients.

Post-tubercular Left Lung Destruction With Compensatory Hyperinflation of the Right Lung: A Complicated Case.

Hyperinflation is the rise in functional residual capacity, i.e., the volume of air left in the lung after normal expiration. One lung is wholly damaged and nonfunctional, while the other lung increases its surface area to compensate for the loss of the respiratory system. Pulmonary tuberculosis (TB) is a respiratory disease caused by Mycobacterium tuberculosis, primarily targeting the lungs. However, if left untreated, it could lead to life-threatening conditions, such as systemic manifestations, and increase the mortality rate. When TB causes severe damage to one lung, the other lung may compensate by hyperinflating excessively to keep the body's oxygenation levels healthy. It was seen in the case of a 60-year-old male who presented to the Outpatient Department (OPD) with complaints of hearing loss, blood-tinged sputum, and cough. In investigations, compensatory hyperinflation was seen. TB and hyperinflation of the lung are not associated together, and hyperinflation is not a clinical sign of TB. This distinction is what distinguishes this particular case.

Quantitative PET imaging and modeling of molecular blood-brain barrier permeability.

Blood-brain barrier (BBB) disruption is involved in the pathogenesis and progression of many neurological and systemic diseases. Non-invasive assessment of BBB permeability in humans has mainly been performed with dynamic contrast-enhanced magnetic resonance imaging, evaluating the BBB as a structural barrier. Here, we developed a novel non-invasive positron emission tomography (PET) method in humans to measure the BBB permeability of molecular radiotracers that cross the BBB through different transport mechanisms. Our method uses high-temporal resolution dynamic imaging and kinetic modeling to jointly estimate cerebral blood flow and tracer-specific BBB transport rate from a single dynamic PET scan and measure the molecular permeability-surface area (PS) product of the radiotracer. We show our method can resolve BBB PS across three PET radiotracers with greatly differing permeabilities, measure reductions in BBB PS of 18F-fluorodeoxyglucose (FDG) in healthy aging, and demonstrate a possible brain-body association between decreased FDG BBB PS in patients with metabolic dysfunction-associated steatotic liver inflammation. Our method opens new directions to efficiently study the molecular permeability of the human BBB in vivo using the large catalogue of available molecular PET tracers.

Lateral Pancreaticojejunostomy in a Rare Case of Chronic Calcific Pancreatitis With Peripancreatic Pseudocyst in an 18-Year-Old Male: A Case Report.

Another name for the Puestow surgery is a lateral pancreaticojejunostomy. The primary pancreatic duct, which runs from the head to the tail of the organ, is opened, exposing the pancreas. In order to allow the pancreas to empty straight into the intestines, the opening of the pancreatic duct is subsequently joined to a tiny intestinal loop. For more than 50 years, this process has been used to effectively relieve pain caused by chronic pancreatitis. This technique has a very low mortality rate and a low rate of surgical complications, and a high success rate. The gradual fibrosis of the pancreas resulting in the loss of exocrine and endocrine function is known as chronic pancreatitis. Intense pain is the disease's most typical symptom. It is unclear what causes the discomfort in chronic pancreatitis. Nonetheless, a large number of these patients have dilated ducts that are made up of intervening structures and saccular dilations, a condition known as the "chain of lakes" phenomenon. Radiological investigations can be used for diagnosis in these patients. Lateral pancreaticojejunostomy is the most effective treatment option for these individuals. Preservation of endocrine and exocrine pancreatic function is another benefit of lateral pancreaticojejunostomy. With lateral pancreaticojejunostomy, chronic fibrocalcific pancreatitis that manifests as pancreatic ductal dilatation and persistent discomfort can be effectively treated. Excellent early outcomes have been observed in terms of pain alleviation as well as post-operative morbidity and mortality; however, the patient's overall outcome and long-term follow-up have not been as well defined.

Lung Metastases in Endometrial Carcinoma: A Deadly Twist.

This case report describes the clinical course of a 73-year-old postmenopausal female presenting with a persistent cough, breathlessness, and hypertension. Upon examination, she exhibited signs of respiratory distress, prompting transfer to the intensive care unit (ICU) where type 1 respiratory failure was diagnosed. Chest imaging revealed bilateral lung opacities, leading to a diagnosis of lung metastasis. Subsequent screening investigations unveiled endometrial carcinoma with atypical respiratory symptoms, highlighting the importance of thorough evaluation. Despite prompt management and biopsy confirmation, the patient's condition rapidly deteriorated, underscoring the aggressive nature of metastatic endometrial carcinoma. This case underscores the necessity of considering atypical presentations and timely intervention in managing such malignancies.

Chilaiditi Sign: A Rare Radiographic Encounter and Diagnostic Exploration.

This case report explores the complex diagnostic dilemma between the Chilaiditi sign and the pneumoperitoneum. The patient presented with chronic complaints of vague abdominal pain, abdominal distension, and breathlessness. A chest X-ray indicated an elevated right hemidiaphragm with transverse colon interposition, leading to the diagnosis of Chilaiditi's sign. Subsequent imaging, including abdominal ultrasound and contrast-enhanced computed tomography, revealed a large non-enhancing multilobulated multicystic mass adherent to the anterior wall of the uterus, raising suspicions of malignancy. Managed by gynecologists, the patient underwent a total abdominal hysterectomy, mass excision, and bilateral salpingo-oophorectomy. The discussion delves into Chilaiditi's sign, its historical context, and its complex pathophysiology involving intestinal, hepatic, and/or diaphragmatic components. Various anatomical and functional factors contributing to this condition are explored. This case highlights the importance of considering the Chilaiditi sign in patients with radiologic evidence of subdiaphragmatic air. It emphasizes the need for timely and accurate diagnosis to differentiate it from more severe conditions like pneumoperitoneum. Such consideration aids in optimizing management strategies and preventing unnecessary investigations.

A Case of Recurrent Sputum-Positive Pulmonary Tuberculosis Presenting With Pulmonary Mycetoma.

Pulmonary tuberculosis is a notorious disease as it can cause severe morbidity and mortality. In this case, we discuss a 75-year-old male tuberculosis patient from a rural area with no underlying comorbidities who failed to continue anti-tubercular medication after two months. The case discusses the diagnostic modalities confirming the diagnosis, sputum culture for Mycobacterium tuberculosis, imaging studies, including X-ray and CT of the chest, and laboratory parameters for identifying pulmonary mycetoma. The patient is now on anti-tubercular therapy (isoniazid, rifampicin, pyrazinamide, and ethambutol combination) and the anti-fungal drug itraconazole. Though pharmacotherapy for the treatment of mycetoma in patients with tuberculosis has a minimal role, the more appropriate treatment is surgical excision via lobectomy. As the occurrence of tuberculosis and mycetoma is a rare phenomenon, it is essential to rule out aspergillosis as both have similar presenting symptoms. Diagnosis of this co-infection can be the crucial difference between morbidity and mortality.

Hyperinsulinemic State and Hypokalemic Quadriparesis in Tropical Fever: Is There a Link?

It is rare for quadriparesis to manifest as a symptom of tropical illnesses. With a history of only one fever episode one week prior, our patient, a 48-year-old male with obesity and prediabetes, who was also known to have ankylosing spondylitis, presented with acute onset flaccid quadriparesis. He did not exhibit any additional symptoms of dengue, such as bleeding tendencies, petechial rashes, thrombocytopenia, or febrile episodes. Upon examination, it was discovered that he had extremely low serum potassium levels and was dengue non-specific antigen 1 (NS1) positive. His hyperinsulinemia, as seen by elevated C peptide levels, most likely caused a transcellular shift that was then triggered by the dengue infection, leading to hypokalemic paralysis.

Chylothorax Chronicles: Tubercular Lymphadenopathy and Hemophagocytic Lymphohistiocytosis.

Chylothorax delineates a state marked by the accumulation of chyle, an opalescent fluid laden with lipids, within the pleural cavity. This occurrence commonly ensues from the seepage of chyle originating from the thoracic duct, occasioned by trauma, surgical interventions, or underlying pathological conditions. This phenomenon induces respiratory distress, necessitating intricate and tailored interventions for its resolution. In this report, we present the case of a 27-year-old male who was admitted with a two-month history of symptoms, including dry cough, weakness, weight loss, and intermittent fever. Previously treated for pleural effusions and ascites, he was referred to our hospital with an intercostal drainage tube in place. Initial examinations revealed respiratory distress, fever, and bilateral pleural effusions. Laboratory results and fluid analysis indicated significant abnormalities, prompting further investigations, including CT scans and biopsies. The patient was diagnosed with chylothorax with chylous ascites due to abdominal tubular lymphadenopathy and hemophagocytic lymphohistiocytosis (HLH) and started on anti-tubercular therapy (AKT4) and octreotide. The patient was also initially managed with non-invasive ventilatory (NIV) support, intravenous antibiotics, nebulizations, an intercostal chest drain (ICD), and a thoracic duct embolization (TDE). Regular monitoring and collaboration between specialties were crucial, ultimately resulting in the removal of the drainage tube and the patient's stable discharge.

Inducing vulnerability to InhA inhibition restores isoniazid susceptibility in drug-resistant Mycobacterium tuberculosis.

Of the approximately 10 million cases of Mycobacterium tuberculosis (Mtb) infections each year, over 10% are resistant to the frontline antibiotic isoniazid (INH). INH resistance is predominantly caused by mutations that decrease the activity of the bacterial enzyme KatG, which mediates the conversion of the pro-drug INH to its active form INH-NAD. We previously discovered an inhibitor of Mtb respiration, C10, that enhances the bactericidal activity of INH, prevents the emergence of INH-resistant mutants, and re-sensitizes a collection of INH-resistant mutants to INH through an unknown mechanism. To investigate the mechanism of action of C10, we exploited the toxicity of high concentrations of C10 to select for resistant mutants. We discovered two mutations that confer resistance to the disruption of energy metabolism and allow for the growth of Mtb in high C10 concentrations, indicating that growth inhibition by C10 is associated with inhibition of respiration. Using these mutants as well as direct inhibitors of the Mtb electron transport chain, we provide evidence that inhibition of energy metabolism by C10 is neither sufficient nor necessary to potentiate killing by INH. Instead, we find that C10 acts downstream of INH-NAD synthesis, causing Mtb to become particularly sensitive to inhibition of the INH-NAD target, InhA, without changing the concentration of INH-NAD or the activity of InhA, the two predominant mechanisms of potentiating INH. Our studies revealed that there exists a vulnerability in Mtb that can be exploited to render Mtb sensitive to otherwise subinhibitory concentrations of InhA inhibitor.IMPORTANCEIsoniazid (INH) is a critical frontline antibiotic to treat Mycobacterium tuberculosis (Mtb) infections. INH efficacy is limited by its suboptimal penetration of the Mtb-containing lesion and by the prevalence of clinical INH resistance. We previously discovered a compound, C10, that enhances the bactericidal activity of INH, prevents the emergence of INH-resistant mutants, and re-sensitizes a set of INH-resistant mutants to INH. Resistance is typically mediated by katG mutations that decrease the activation of INH, which is required for INH to inhibit the essential enzyme InhA. Our current work demonstrates that C10 re-sensitizes INH-resistant katG-hypomorphs without enhancing the activation of INH. We furthermore show that C10 causes Mtb to become particularly vulnerable to InhA inhibition without compromising InhA activity on its own. Therefore, C10 represents a novel strategy to curtail the development of INH resistance and to sensitize Mtb to sub-lethal doses of INH, such as those achieved at the infection site.

Synthesis of Three-Dimensional Ring Fused Heterocycles by a Selective [4 + 2] Cycloaddition Between Bicyclic Thiazolo 2-Pyridones and Arynes.

A selective [4 + 2] cycloaddition reaction of thiazolo-2-pyridones with arynes has been demonstrated. The developed protocol allows rapid access to highly functionalized, structurally complex thiazolo-fused bridged isoquinolones in high yields, which are susceptible to further late-stage functionalization.

A Clinical Encounter With Intrathoracic Extrapulmonary Hydatid Disease.

Intrathoracic extrapulmonary hydatid disease is an uncommon variant of hydatidosis. In this report, we describe a rare case of a 53-year-old female who presented with a left-side massive hydropneumothorax, initially treated as tubercular empyema and later came out to be intrathoracic extrapulmonary hydatid disease, with no signs of primary lesion in the lung. This case was managed with an intercostal drain insertion followed by a thoracoscopic-guided excision of the cyst, which on histopathological examination confirmed the diagnosis. Also, the Echinococcus antibody IgG test confirmed the same. The patient was then initiated on oral albendazole which showed a drastic reduction in the intrapleural cysts, but the patient later developed non-resolving pyopneumothorax with a bronchopleural fistula. The patient is being managed conservatively at present with oral albendazole and chest drain and is later advised to undergo decortication surgery of the lung.

Successful Surgical Management of Chronic Lower Limb Lymphedema: A Case Report.

Chronic lower limb lymphedema is a challenging and often debilitating medical condition characterized by the abnormal accumulation of lymphatic fluid in the extremities, leading to persistent swelling and discomfort. While this condition can be caused by various underlying factors, early diagnosis, and appropriate management are crucial for improving the patient's quality of life. This case report presents the successful surgical management of chronic lower limb lymphedema in a 30-year-old male patient who had been grappling with this condition for a decade. The patient's journey from the onset of symptoms, including swelling and difficulty in walking, to the eventual diagnosis and treatment is documented herein. Despite seeking medical care from allopathic and homeopathic sources, the patient's condition continued to deteriorate over the years, underscoring the complexity of chronic lower limb lymphedema and its challenges in clinical management. This case highlights the importance of accurate diagnosis, multidisciplinary evaluation, and a comprehensive surgical approach in addressing the complexities of chronic lower limb lymphedema. It also sheds light on the potential complications that may arise during treatment and the postoperative care required to achieve a favorable outcome. By sharing this case, we aim to contribute to understanding this condition and provide insights into the effective management of chronic lower limb lymphedema.

Oscillometry in Lung Function Assessment: A Comprehensive Review of Current Insights and Challenges.

Oscillometry, a non-invasive technique for assessing lung function, has gained significant recognition and importance in modern pulmonary medicine. This comprehensive review thoroughly explores its principles, applications, advantages, limitations, recent innovations, and future directions. Oscillometry's primary strength lies in its ability to offer a holistic assessment of lung mechanics. Unlike traditional spirometry, oscillometry captures the natural airflow during quiet breathing, making it suitable for patients of all ages and those with severe respiratory conditions. It provides a comprehensive evaluation of airway resistance, reactance, and compliance, offering insights into lung function that were previously challenging to obtain. In clinical practice, oscillometry finds extensive application in diagnosing and managing respiratory diseases. It plays a pivotal role in asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases. By detecting subtle changes in lung function before symptoms manifest, oscillometry facilitates early interventions, improving disease management and patient outcomes. Oscillometry's non-invasive and patient-friendly nature is precious in pediatric care, where traditional spirometry may be challenging for young patients. It aids in diagnosing and monitoring pediatric respiratory disorders, ensuring that children receive the care they need from an early age. Despite its many advantages, oscillometry faces challenges, such as the need for standardized protocols and the complexity of data interpretation. However, ongoing efforts to establish global standards and provide education and training for healthcare professionals aim to address these issues. Looking ahead, oscillometry holds great promise in the field of personalized medicine. With its ability to tailor treatment plans based on individualized lung function data, healthcare providers can optimize therapy selection and dosing, ultimately improving patient care and quality of life. In conclusion, oscillometry is poised to play an increasingly pivotal role in modern pulmonary medicine. As standardization efforts continue and technology evolves, it is an indispensable tool in the clinician's arsenal for diagnosing, managing, and personalizing respiratory care, ultimately leading to improved patient outcomes and better respiratory health.

Controlled Noncovalent Synthesis of Secondary Supramolecular Polymers.

Dynamic supramolecular polymers, with their functional similarities to classical covalent polymers and their adaptive and self-repairing nature reminiscent of biological assemblies, have emerged as highly promising systems for the design of smart soft materials. Recent advancements in mechanistic investigations and novel synthetic strategies, such as living supramolecular polymerization, have significantly enhanced our ability to control the primary structure of these supramolecular polymers. However, realizing their full functional potential requires expanding their topological diversity in a manner akin to classical polymers as well as achieving precise molecular organization at higher hierarchical levels of self-assembly. In this paper, we present a remarkable advancement in this field, introducing an unprecedented and controlled synthesis of secondary supramolecular polymers. Our innovative strategy combines chirality-controlled surface-catalyzed secondary nucleation and a bioinspired peptide design, effectively stabilizing higher-order assembly. Furthermore, by harnessing this stereoselective nucleation process, we demonstrate the successful synthesis of racemic supramolecular polymers featuring parallelly stacked conglomerate microstructures─a previously unreported topology in synthetic self-assembled systems. Additionally, we elucidate that the extent of secondary supramolecular polymers can be regulated by modulating the enantiomeric excess of the chiral monomers. Consequently, our study unveils new topologies that exhibit enhanced higher-order structural complexity in the realm of supramolecular polymers.

Improved Detection of Fibrotic Nonalcoholic Fatty Liver Disease in Community-Based Referrals.

Background: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease with increasing rates globally. Patients with type 2 diabetes mellitus have higher risk of developing NAFLD. Patients with a higher degree of liver fibrosis in NAFLD are at an increased risk for liver-related mortality, but get missed easily during the referral process. This project aims to improve early detection and linkage-to-care of fibrotic NAFLD patients. Methods: We utilized a combination of automated electronic health record (EHR)-based fibrosis (FIB)-4 score and directed provider education. A health-system wide FIB-4 score calculator that providers can easily add to their workflow for NAFLD patient triaging. Data were analyzed at 6 and 12 months after implementation. Results: Postimplementation, there was an increase in patients referred to hepatology with higher degree of liver fibrosis and decreased referral to hepatology with low risk of liver fibrosis, measured by FIB-4 score. At baseline, ∼55% of referred patient to hepatology had FIB-4 score <1.3 compared to 38% at 12 months postimplementation. There was an increase in referral of patients with FIB-4 scores >1.3 when compared to preinterventions, 62% versus 45%. This is most pronounced in patients with severe fibrotic disease with FIB-4 score >2.67, 30% versus 12%. Conclusions: Automated FIB-4 score in EHR can improve appropriate linkage-to-care for at-risk fibrotic NAFLD, especially when coupled with targeted provider education. The durability of such improvement is essential to study along with the need to increase broad acceptance across health systems.

Design, Synthesis, and Evaluation of Novel Δ2-Thiazolino 2-Pyridone Derivatives That Potentiate Isoniazid Activity in an Isoniazid-Resistant Mycobacterium tuberculosis Mutant.

Mycobacterium tuberculosis (Mtb) drug resistance poses an alarming threat to global tuberculosis control. We previously reported that C10, a ring-fused thiazolo-2-pyridone, inhibits Mtb respiration, blocks biofilm formation, and restores the activity of the antibiotic isoniazid (INH) in INH-resistant Mtb isolates. This discovery revealed a new strategy to address INH resistance. Expanding upon this strategy, we identified C10 analogues with improved potency and drug-like properties. By exploring three heterocycle spacers (oxadiazole, 1,2,3-triazole, and isoxazole) on the ring-fused thiazolo-2-pyridone scaffold, we identified two novel isoxazoles, 17h and 17j. 17h and 17j inhibited Mtb respiration and biofilm formation more potently with a broader therapeutic window, were better potentiators of INH-mediated inhibition of an INH-resistant Mtb mutant, and more effectively inhibited intracellular Mtb replication than C10. The (-)17j enantiomer showed further enhanced activity compared to its enantiomer and the 17j racemic mixture. Our potent second-generation C10 analogues offer promise for therapeutic development against drug-resistant Mtb.

Persistent Winking Coronary Sign in a Case of Post-myocardial Infarction Ventricular Septal Rupture After Device Closure.

A winking coronary sign refers to the partial collapse of an artery situated over the ventricular septal rupture during systole and refilling of the same during diastole, which is seen as phasic filling and disappearance of the arterial segment during coronary angiography. In this article, we discuss the case of a patient who reported to the emergency department of a tertiary care hospital in central India with myocardial infarction of the anterior wall. Two-dimensional echocardiography and coronary angiography revealed ventricular septal rupture. The patient was promptly managed by a percutaneous coronary angiography and interventricular septal device closure. Even after the defect closure, the winking coronary sign persisted on coronary angiography, and the patient was then discharged in stable condition.