Abstract Background Interstitial lung abnormalities (ILA) are radiologic findings that may progress to idiopathic pulmonary fibrosis (IPF). Blood gene expression profiles can predict IPF mortality, but whether these same genes associate with ILA and ILA outcomes is unknown. This study evaluated if a previously described blood gene expression profile associated with IPF mortality is associated with ILA and all-cause mortality. Methods In COPDGene and ECLIPSE study participants with visual scoring of ILA and gene expression data, we evaluated the association of a previously described IPF mortality score with ILA and mortality. We also trained a new ILA score, derived using genes from the IPF score, in a subset of COPDGene. We tested the association with ILA and mortality on the remainder of COPDGene and ECLIPSE. Results In 1469 COPDGene (training n = 734; testing n = 735) and 571 ECLIPSE participants, the IPF score was not associated with ILA or mortality. However, an ILA score derived from IPF score genes was associated with ILA (meta-analysis of test datasets OR 1.4 [95% CI: 1.2–1.6]) and mortality (HR 1.25 [95% CI: 1.12–1.41]). Six of the 11 genes in the ILA score had discordant directions of effects compared to the IPF score. The ILA score partially mediated the effects of age on mortality (11.8% proportion mediated). Conclusions An ILA gene expression score, derived from IPF mortality-associated genes, identified genes with concordant and discordant effects on IPF mortality and ILA. These results suggest shared, and unique biologic processes, amongst those with ILA, IPF, aging, and death.
A case of disseminated Burkitt's lymphoma with nervous system involvement in a HIV negative 35 year old lady is described. She primarily presented with multiple cranial nerve palsies. At autopsy, diffuse involvement of parenchymatous organs and lymphomatous meningitis with conspicuous sparing of gastrointestinal system was observed. In addition, there was an unusual feature of paraneoplastic demyelinating peripheral neuropathy. Incidentally, a large hydatid cyst was also seen in the left lobe in addition to the lymphomatous involvement of the liver.
Scrub typhus is a rickettsial infection prevalent in most parts of India. Acute pancreatitis with pseudocyst formation is a rare complication of this condition. This paper reports acute renal failure, pancreatitis and pseudocyst formation in a 48-year-old female with scrub typhus. Ultrasonography of the abdomen revealed a bulky pancreas with fluid seen along the body of the pancreas in the lesser sac. The infection was successfully treated with doxycycline and supportive treatment. Pancreatitis was managed conservatively. This case report highlights the importance of identifying and managing uncommon complications of a common tropical disease for optimum outcome.
Bupropion is a norepinephrine-dopamine reuptake inhibitor that is commonly used as an antidepressant and for smoking cessation. Bupropion overdose can lead to serious side effects which include seizures, status epilepticus, and fatal arrhythmias. Managing bupropion toxicity is challenging as there is no effective antidote and treatment is largely supportive. In this article, we present a case of bupropion toxicity causing profound cardiogenic shock which was treated successfully with mechanical circulatory support.
Rationale: In addition to rare genetic variants and the MUC5B locus, common genetic variants contribute to idiopathic pulmonary fibrosis (IPF) risk. The predictive power of common variants outside the MUC5B locus for IPF and interstitial lung abnormalities (ILAs) is unknown. Objectives: We tested the predictive value of IPF polygenic risk scores (PRSs) with and without the MUC5B region on IPF, ILA, and ILA progression. Methods: We developed PRSs that included (PRS-M5B) and excluded (PRS-NO-M5B) the MUC5B region (500-kb window around rs35705950-T) using an IPF genome-wide association study. We assessed PRS associations with area under the receiver operating characteristic curve (AUC) metrics for IPF, ILA, and ILA progression. Measurements and Main Results: We included 14,650 participants (1,970 IPF; 1,068 ILA) from six multi-ancestry population-based and case–control cohorts. In cases excluded from genome-wide association study, the PRS-M5B (odds ratio [OR] per SD of the score, 3.1; P = 7.1 × 10−95) and PRS-NO-M5B (OR per SD, 2.8; P = 2.5 × 10−87) were associated with IPF. Participants in the top PRS-NO-M5B quintile had ∼sevenfold odds for IPF compared with those in the first quintile. A clinical model predicted IPF (AUC, 0.61); rs35705950-T and PRS-NO-M5B demonstrated higher AUCs (0.73 and 0.7, respectively), and adding both genetic predictors to a clinical model yielded the highest performance (AUC, 0.81). The PRS-NO-M5B was associated with ILA (OR, 1.25) and ILA progression (OR, 1.16) in European ancestry participants. Conclusions: A common genetic variant risk score complements the MUC5B variant to identify individuals at high risk of interstitial lung abnormalities and pulmonary fibrosis.
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