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Nintedanib is a tyrosine kinase inhibitor that was approved for the treatment of patients with idiopathic pulmonary fibrosis in 2014. The most common side effect of Nintedanib is diarrhea, and thrombocytopenia is a rare side effect of Nintedanib. The exact mechanism is unknown, and the literature lacks case reports of this phenomenon. Here, we report the case of a patient who developed thrombocytopenia 12 weeks after starting treatment with Nintedanib. The patient underwent an extensive work up for infectious, hematological, autoimmune, and neoplastic diseases. The patient's thrombocytopenia resolved following cessation of Nintedanib. This case is significant as it reports a rare side effect that might have detrimental consequences if not recognized and treated timely. Additionally, the onset of thrombocytopenia was delayed, 3 months after the initiation of Nintedanib. We also highlight the various literature regarding drug-induced thrombocytopenia and explore the necessary work-up needed to exclude other potential diagnoses. We hope to advocate for multidisciplinary teams to be aware of patients with pulmonary fibrosis on Nintedanib so that this adverse effect can be recognized promptly. [ABSTRACT FROM AUTHOR]

Rationale: Chronic obstructive pulmonary disease (COPD) is a well-established independent risk factor for lung cancer; however, the literature on the association between asthma and lung cancer is mixed. Whether asthma-COPD overlap (ACO) is associated with lung cancer has not been studied. Objectives: We aimed to compare lung cancer risk among patients with ACO versus COPD and other conditions associated with airway obstruction. Methods: We studied 13,939 smokers from the National Lung Cancer Screening Trial who had baseline spirometry and used spirometric indices and history of childhood asthma to categorize participants into five specific airway disease subgroups. We used Poisson regression to compare unadjusted and adjusted lung cancer risk. Results: The incidence rate of lung cancer per 1,000 person-years was as follows: ACO, 13.2 (95% confidence interval [CI], 8.1-21.5); COPD, 11.7 (95% CI, 10.5-13.1); asthmatic smokers, 1.8 (95% CI, 0.6-5.4); Global Initiative for Chronic Obstructive Lung Disease-Unclassified, 7.7 (95% CI, 6.4-9.2); and normal spirometry smokers, 4.1 (95% CI, 3.5-4.8). Patients with ACO had increased adjusted risk of lung cancer compared with patients with asthma (incidence rate ratio [IRR], 4.5; 95% CI, 1.3-15.8) and normal spirometry smokers (IRR, 2.3; 95% CI, 1.3-4.2) in models adjusting for other risk factors. Adjusted lung cancer incidence in patients with ACO and COPD were not found to be different (IRR, 1.2; 95% CI, 0.7-2.1). Conclusions: The risk of lung cancer among patients with ACO is similar to those with COPD and higher than other groups of smokers. These results provide further evidence that COPD, with or without a history of childhood asthma, is an independent risk factor for lung cancer. [ABSTRACT FROM AUTHOR]

Background: Metformin-associated lactic acidosis (MALA) is a relatively rare adverse effect of metformin therapy. It usually occurs in patients with metformin overdose or in those with underlying acute and/or chronic conditions resulting in impaired lactate metabolism. Among these, patients with acute kidney injury, heart failure, sepsis, and cirrhosis are the most vulnerable to MALA, even in the setting of appropriate therapy. The most common symptoms of MALA include nausea, vomiting, diarrhea, encephalopathy, hypothermia, respiratory failure, and hypotension. Blindness is a dramatic symptom that has been rarely reported with MALA. Case Report: We report a case of 78-year-old woman with history of type 2 diabetes mellitus with nephropathy for which she was treated with metformin and insulin. She developed nausea, non-bloody emesis, and watery diarrhea, which led to dehydration, anion gap metabolic acidosis due to hyperlactatemia, and acute kidney injury (AKI). She was hospitalized for i.v. hydration and further management when she suddenly developed blindness. The diagnostic work-up ruled out central causes and her symptoms resolved briefly after continuous renal replacement therapy (CRRT) was initiated, confirming the diagnosis of MALA. Conclusions: By reporting this case, we wish to increase awareness about MALA symptoms, its diagnosis, and the importance of early recognition and initiation of treatment among clinicians involved in the care of patients with chronic kidney disease (CKD) who take metformin for diabetes mellitus. Although rare, this metformin adverse effect can present dramatically and can be distressing for both patient and treating team. [ABSTRACT FROM AUTHOR]

Recent advances in fibrotic hypersensitivity pneumonitis include improved diagnostic guidance, systematic assessments of immunosuppressive therapy, and the recent availability of antifibrotic therapy (nintedanib) for those with progressive disease. A standardized approach to diagnosis may lead to better inclusion criteria for future therapeutic protocols and delineation of disease or treatment response predictors for real-world management. This review will highlight current diagnostic and treatment challenges and remaining knowledge gaps or areas of uncertainty, with a practical overview of supporting evidence and its clinical implications. Exposure history, serologic testing for antigen sensitivity, bronchoalveolar lavage lymphocytosis, histopathology, and radiologic findings will be covered in the diagnosis section, with immunosuppression, antifibrotic therapy, lung transplantation, and disease prognosis in the treatment and management section. [ABSTRACT FROM AUTHOR]

Rationale: Prior research studies on the association of obstructive sleep apnea (OSA) and pain intensity have examined older patients; there is a need to understand the relationship between OSA and pain intensity among younger adults.Objectives: To examine whether young adults with diagnosed OSA are more likely to report higher pain intensity compared with those without OSA.Methods: We conducted a cross-sectional analysis of a cohort study of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn veterans who had at least one visit to a Veterans Health Administration primary care clinic between 2001 and 2014. OSA was identified using one inpatient or two outpatient International Classification of Diseases, Ninth Revision codes from electronic medical records. Average pain intensity (based on the self-reported 0-10 numeric rating scale over a 12-month period) was categorized as no pain/mild (0-3; no pain) and moderate/severe (4-10; significant pain). Covariates included age, sex, education, race, mental health diagnoses, headache diagnoses, pain diagnoses, hypertension, diabetes, body mass index, and smoking status. Multivariate logistic regression models were used, and multiple imputation was performed to generate values for missing variables.Results: We identified 858,226 young adults (mean age 30 yr [SD = 7]), of whom 91,244 (10.6%) had a diagnosis of OSA and 238,587 (27.8%) reported moderate/severe pain for the 12-month average. with young adults without OSA, those with OSA were more likely to report moderate/severe pain intensity (adjusted odds ratio, 1.09; 95% confidence interval, 1.08-1.11) even after controlling for covariates.Conclusions: We found that young adults with OSA have greater odds of comorbid moderate/severe pain. Because of the high prevalence of chronic pain in younger adults, this study highlights the need to understand the impact of OSA diagnosis and treatment on pain intensity. Future work is needed to determine the role of effective OSA treatment on pain intensity over time in these young adults. [ABSTRACT FROM AUTHOR]

The article reviews the progress made in 2019 on understanding childhood asthma epidemiology and risk factors, mechanisms underpinning different disease subtypes, therapeutic options and prediction of treatment responses. It mentions that factors contributing to poor asthma control, exacerbations, and mortality include individual characteristics and environmental exposures; and also mentions about the use of machine learning and bioinformatics.

Rhabdomyolysis is a serious complication of statin treatment. Both higher statin doses and pharmacokinetic factors can raise statin levels, leading to this serious usclerelated syndrome. Co-administration of statins with drugs that are strong inhibitors of cytochrome P450 (CYP) 3A4 (the main cytochrome P450 isoform that metabolizes most statins) can increase statin levels several fold. The trigger for our patient's statin-induced rhabdomyolysis was fluconazole, a known moderate inhibitor of CYP3A4, which is comparatively weaker than certain potent azoles like itraconazole or ketoconazole. [ABSTRACT FROM AUTHOR]

The article presents a case study of 76-year-old white female with 7-day history of weakness and pain in her arms and legs who was diagnosed with rhabdomyolysis, a complication of statin treatment. Topics discussed include the use of magnetic resonance imaging (MRI) for diagnosis, the trigger of statin-induced rhabdomyolysis by fluconazole, and the simvastatin-fluconazole drug interaction.

Calcium pyrophosphate deposition disease (CPPD) is a crystal arthropathy associated with diverse and numerous risk factors including age, genetic mutations in the ankylosis homolog gene, previous trauma to the joint, osteoarthritis, hypophosphatasia (an inherited metabolic bone disorder), hyperparathyroidism, hemochromatosis, hypomagnesemia, and monosodium urate gout. Here, a 77-year-old man with a complicated history of inflammatory arthritis presented with an acute episode of debilitating polyarticular arthritis with marked deviation in endocrine markers and electrolytes. While autoimmune, infectious, and reactive arthropathies were considered, arthrocentesis revealed calcium pyrophosphate crystals, leading to diagnosis of acute calcium pyrophosphate disease. This patient's acute symptomatic calcium pyrophosphate disease was thought to be precipitated by metabolic derangements involving calcium and magnesium. hese derangements likely occurred secondary to poor oral intake, malnutrition, and renal wasting syndrome, and were resistant to treatment with electrolyte repletion. [ABSTRACT FROM AUTHOR]

The article presents the case study of a 51 year old women with primary biliary cirrhosis with two previous liver transplants, current chronic liver rejection, progressive chronic kidney disease and underwent combined liver–kidney transplantation. The surgery was complicated because of hemorrhagic shock and cardiopulmonary arrest.

Objective The specific link between obstructive sleep apnea (OSA) and pain is unknown, but it has been hypothesized that OSA patients are hyperalgesic because of fragmented sleep and hypoxemia that enhance sensitivity to pain, promote inflammation, and increase spontaneous pain. We conducted a systematic review of the literature assessing whether OSA is a risk factor for subjective pain intensity and experimental pain tolerance and threshold. Design/Participants A search of published studies in English in MEDLINE, PubMed, Embase, and the Cochrane Database of Systematic Reviews from database inception through May 2017 was performed. Search terms included “sleep apnea,” “continuous positive airway pressure,” “CPAP,” “pain,” and “chronic pain.” Methods We included any study that reported an association between OSA or polysomnogram assessments with pain outcomes or reported the effect of CPAP on pain outcomes. Controlled studies, cohort studies, and case–control studies were included. Results We identified 448 studies from PubMed and 959 studies from Embase, giving a combined 1,333 studies after removing duplicates. After detailed selection, 28 articles were reviewed in full and 12 met study inclusion criteria. Whereas several studies found an association between OSA and pain intensity or experimental pain, there was considerable variability among study outcomes. Delivery of CPAP may improve pain and decrease opioid use, although the exact nature of the relationship between pain and the various pathophysiologic components of OSA is unclear. Conclusions This systematic review summarizes the current evidence for the association of OSA and pain outcomes. Further research is needed to identify the differential effects of nocturnal hypoxemia and fragmented sleep on pain intensity. Clinicians might consider screening patients with chronic pain for OSA. [ABSTRACT FROM AUTHOR]

Acute heart failure hospitalizations complicated by diuretic resistance are associated with worse outcomes. Yet, quantification of the frequency and accompanying risk from loop diuretic resistance is limited by the absence of a comprehensive definition with universal clinical application. Herein, we outline limitations of the current metrics used to identify and define diuretic resistance. We discuss the best available methods to identify and prognosticate outcomes in diuretic resistance. We propose a mechanism-based classification system of diuretic resistance by anatomical location as follows: pre-nephron resistance, pre-loop of Henle resistance, loop of Henle resistance, and post-loop of Henle resistance. Within this paradigm, we compare and contrast historical beliefs of resistance mechanisms with current literature specific to patients with heart failure. We recommend a treatment pathway to restore diuretic efficacy with a literature review of the various combination diuretic strategies and ongoing clinical trials that may impact current best practices. [ABSTRACT FROM AUTHOR]