Predicting drug outcome of population via clinical knowledge graph.

Optimal treatments depend on numerous factors such as drug chemical properties, disease biology, and patient characteristics to which the treatment is applied. To realize the promise of AI in healthcare, there is a need for designing systems that can capture patient heterogeneity and relevant biomedical knowledge. Here we present PlaNet, a geometric deep learning framework that reasons over population variability, disease biology, and drug chemistry by representing knowledge in the form of a massive clinical knowledge graph that can be enhanced by language models. Our framework is applicable to any sub-population, any drug as well drug combinations, any disease, and to a wide range of pharmacological tasks. We apply the PlaNet framework to reason about outcomes of clinical trials: PlaNet predicts drug efficacy and adverse events, even for experimental drugs and their combinations that have never been seen by the model. Furthermore, PlaNet can estimate the effect of changing population on the trial outcome with direct implications on patient stratification in clinical trials. PlaNet takes fundamental steps towards AI-guided clinical trials design, offering valuable guidance for realizing the vision of precision medicine using AI.

Therapeutic management of Mycobacterium avium subspecies paratuberculosis infection with complete resolution of symptoms and disease in a patient with advanced inflammatory bowel syndrome.

BACKGROUND: A 26-year-old male had a history of frequent bowel movements, mushy stool with mucus and loss of 25 kg body weight in 6 months was diagnosed as a case of inflammatory bowel disease (IBD). The patient did not respond to routine and standard treatment for IBD. His condition was steadily deteriorating, and he was in a very precarious state when he reported to us. METHODS: Upon laboratory investigation by using IS900 specific PCR [which is specific for Mycobacterium avium subspecies paratuberculosis (MAP)], the blood and stool samples were found negative. However, the presence of low titer MAP-antibodies by indigenous ELISA were found followed by detection of the typical acid-fast MAP bacilli (with 3 + or 4 + grade) microscopically. The MAP stool culture was positive after 6 months incubation. The biotyping by IS1311 specific polymerase chain reaction restriction enzyme (PCR-RE) confirmed infection with 'Indian Bison Type Genotype', a dominant biotype infecting the domestic livestock population of India. Standard anti-MAP therapy was initiated under supervision of the treating physician. The drug of choice in prescribed treatment regimen included Isoniazid (5 mg/kg), Rifampicin (10 mg/kg), Ethambutol (15-25 mg/kg) once a day for 24 weeks and Clarithromycin (250 mg)/Levofloxacin (250 mg) twice a day for 6 weeks. RESULTS: Following treatment, the patient started improving progressively with reduction in bowel movement frequency and gained body weight with an enhanced appetite propensity. Upon follow-up of the patient after 1 year of treatment, stool-microscopy and stool-culture were found negative for MAP. Till the recent past, the patient was further monitored for disease relapse, if any. CONCLUSIONS: This patient has experienced a complete resolution of IBD using a combination of anti-MAP antibiotics. The initial detection of heavy shedding of acid-fast MAP bacilli and typical colony morphology with its characterization obtained from culturing of stool sample indicated the infection of MAP. Interestingly, the present case is one more example of the linkage of demonstrable MAP infection treated with anti-MAP therapy in the presence and then absence of disease in the human host.

Isolated Oculomotor Nerve Palsy - A Rare Initial Manifestation of Tuberculous Meningitis.

Tuberculous meningitis (TBM) is a sub-acute / chronic meningitis known for its diverse manifestations which may lead to delayed diagnosis. An isolated oculomotor nerve palsy as an initial presentation of TB meningitis is quite rare. One such case has presented here; A 18 year female presented to us with ptosis of the left eye. Complete neurological examination revealed it to be a case of isolated 3rd cranial nerve palsy. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) brain revealed no significant abnormality. Cerebrospinal fluid (CSF) analysis was done and diagnosis of Tuberculous Meningitis was confirmed. This case report focuses on the fact that tuberculous meningitis should be included in the differential diagnosis of isolated oculomotor nerve palsy.

Should screening voluntary blood donors be used as strategy to diagnose diabetes and diabetic nephropathy?

INTRODUCTION AND AIM: The present study aims to assess the glycemic status during voluntary blood donation as a strategy to detect undiagnosed diabetes mellitus and diabetic nephropathy. MATERIAL AND METHOD: Study was conducted at a tertiary care hospital and medical college. All voluntary blood donors underwent random capillary blood glucose screening and patients who had random blood sugar exceeding 200 mg/dl were subjected to undergo oral glucose tolerance test (OGTT). The subjects thus detected diabetic by capillary blood sugar and OGTT underwent screening diabetic kidney disease with urine albumin to creatnine ratio (UACR). Data collected was statistically analyzed using SPSS 16 using Student's t test. RESULTS: Seven hundred and sixty five males and 443 females were enrolled for the study. Capillary blood sugar of 54 subjects was ≥200 mg/dl. 48 subjects gave consent for OGTT, stratified data showed 22 subjects (12 males and 10 females) were in range of 200-300 mg/dl. 20 subjects (12 males and 8 females) were in range of 300-400 mg/dl, whereas 6 subjects (5 males and 1 female) had blood sugar more than 400 mg/dl. The HbA1C ranges in respective glycemic groups were 200-300 mg/dl - 7.4% to 8.6% (mean - 8.05%), 300-400 mg/dl - 8.7% to 11.8% (mean 9.63%), more than 400 mg/dl - 11.8% to 14.2% (mean - 13%). Male preponderance was observed in all glycemic groups, though the difference was statistically insignificant. Of the 48 diabetic subjects, 13 (27.08%) were detected to have albuminuria, of these 11 (22.91%) had microalbuminuria (UACR 30 - 300 mg/gm), whereas 2 (4.16%) had overt proteinuria (UACR exceeding 300 mg/gm). CONCLUSION: Glycemic screening with random capillary blood glucose screening, 75 gm 2 hour OGTT and HbA1C amongst voluntary blood donors can be used to detect pre diabetes and undiagnosed diabetes mellitus and diabetic nephropathy.

The Consensus from the Mycobacterium avium ssp. paratuberculosis (MAP) Conference 2017.

On March 24 and 25, 2017 researchers and clinicians from around the world met at Temple University in Philadelphia to discuss the current knowledge of Mycobacterium avium ssp. paratuberculosis (MAP) and its relationship to human disease. The conference was held because of shared concern that MAP is a zoonotic bacterium that poses a threat not only to animal health but also human health. In order to further study this problem, the conferees discussed ways to improve MAP diagnostic tests and discussed potential future anti-MAP clinical trials. The conference proceedings may be viewed on the www.Humanpara.org website. A summary of the salient work in this field is followed by recommendations from a majority of the conferees.

Concurrent Resolution of Chronic Diarrhea Likely Due to Crohn's Disease and Infection with Mycobacterium avium paratuberculosis.

Examination of samples of stool from a 61-year-old male patient, presenting with the clinical symptoms of Crohn's disease (CD), revealed massive shedding of acid fast bacilli with the morphology of Mycobacterium avium paratuberculosis (MAP), the causative agent of Johne's disease in cattle. MAP was cultured from the stool. Biotyping of the bacterium isolated from cultures of stool demonstrated, it was the Indian Bison biotype of MAP, the dominant biotype infecting livestock and humans in India. Based on this finding and because the patient was unresponsive to standard therapy used in India to treat patients with gastrointestinal inflammatory disorders, the patient was placed on a regimen of multi-antibiotic therapy, currently used to treat tuberculosis and CD. After 1 year of treatment, the patient's health was restored, concurrent with cessation of shedding of MAP in his stool. This patient is the first case shown to shed MAP from the stool who was cured of infection with antibiotics and who was concurrently cured of clinical signs of CD.