Management of Refractory Chronic Obstructive Pulmonary Disease: A Review.

Chronic obstructive pulmonary disease (COPD) is a common condition with an estimated prevalence of 12% in adults over the age of 30 years worldwide. COPD is a leading cause of morbidity and mortality globally, with a substantial economic and social burden. There are an estimated 3 million deaths annually due to COPD. However, most of the patients with COPD respond to routine interventions like bronchodilator therapy, assessing supplemental oxygen needs, smoking cessation, vaccinations, and pulmonary rehabilitation. There is a significant number of patients who unfortunately progress to have persistent symptoms despite these interventions. Refractory COPD is not yet formally defined. Patients with severe persistent symptoms or exacerbations despite appropriate care can be considered to have refractory COPD. Managing refractory COPD needs a multidimensional approach. In this review article, we will discuss essential interventions like ensuring adequate inhaler techniques, exploring the need for non-invasive ventilatory support, use of chronic antibiotics and phosphodiesterase inhibitors to advanced therapies like bronchoscopic lung volume reduction surgery, and the upcoming role of anti-IL5 agents in managing patients with refractory COPD. We will also discuss non-pharmacologic interventions like psycho-social support and nutritional support. We will conclude by discussing the palliative care aspect of managing patients with refractory COPD. Through this review article, we aim to better the approach to managing patients with refractory COPD and discuss new upcoming therapies.

Role of Therapeutic Anticoagulation in COVID-19: The Current Situation.

Thrombotic complications from COVID-19 are now well known and contribute to significant morbidity and mortality. Different variants confer varying risks of thrombotic complications. Heparin has anti-inflammatory and antiviral effects. Due to its non-anticoagulant effects, escalated-dose anticoagulation, especially therapeutic-dose heparin, has been studied for thromboprophylaxis in hospitalized patients with COVID-19. Few randomized, controlled trials have examined the role of therapeutic anticoagulation in moderately to severely ill patients with COVID-19. Most of these patients had elevated D-dimers and low bleeding risks. Some trials used an innovative adaptive multiplatform with Bayesian analysis to answer this critical question promptly. All the trials were open-label and had several limitations. Most trials showed improvements in the meaningful clinical outcomes of organ-support-free days and reductions in thrombotic events, mainly in non-critically-ill COVID-19 patients. However, the mortality benefit needed to be more consistent. A recent meta-analysis confirmed the results. Multiple centers initially adopted intermediate-dose thromboprophylaxis, but the studies failed to show meaningful benefits. Given the new evidence, significant societies have suggested therapeutic anticoagulation in carefully selected patients who are moderately ill and do not require an intensive-care-unit level of care. There are multiple ongoing trials globally to further our understanding of therapeutic-dose thromboprophylaxis in hospitalized patients with COVID-19. In this review, we aim to summarize the current evidence regarding the use of anticoagulation in patients with COVID-19 infection.

The Impact of Anxiety and Depression in Chronic Obstructive Pulmonary Disease.

Patients with COPD (chronic obstructive pulmonary disease) are at a higher risk of comorbid conditions such as anxiety and/or depression, which in turn increase their symptom burden and rehospitalizations compared to the general population. It is important to investigate the pathophysiology and clinical implications of mental health on patients with COPD. This review article finds that COPD patients with anxiety and/or depression have a higher rehospitalization incidence. It reviews the current screening and diagnosis methods available. There are pharmacological and non-pharmacologic interventions available for treatment of COPD patients with depression based on severity. COPD patients with mild depression benefit from pulmonary rehabilitation and cognitive behavioral therapy, whereas patients with severe or persistent depression can be treated with pharmacologic interventions.

Trends in the Epidemiology and Outcomes of Pneumocystis Pneumonia among Human Immunodeficiency Virus (HIV) Hospitalizations.

Introduction: Pneumocystis Pneumonia (PCP) is a common opportunistic infection among people living with the human immunodeficiency virus (HIV). This study's objective was to assess temporal trends in PCP epidemiology among hospitalized patients with HIV/AIDS in the US and to compare data for hospitalizations with HIV with PCP to those without PCP. Methods: The national inpatient sample (NIS) data were analyzed from 2002−2014. The discharge coding identified hospitalized patients with HIV or AIDS and with or without PCP. Results: We identified 3,011,725 hospitalizations with HIV/AIDS during the study period; PCP was present in 5% of the patients with a diagnosis of HIV. The rates of PCP progressively declined from 6.7% in 2002 to 3.5 % in 2014 (p < 0.001). Overall mortality in patients with HIV was 3.3% and was significantly higher in those with PCP than without PCP (9.9% vs. 2.9%; p < 0.001). After adjusting for demographics and other comorbidities, PCP had higher odds of hospital mortality 3.082 (OR 3.082; 95% CI, 3.007 to 3.159; p < 0.001). Conclusion: From 2002 to 2014, the rate of PCP in HIV patients has decreased significantly in the United States but is associated with substantially higher mortality.

Impact of atrial fibrillation on in-hospital outcomes among hospitalizations for cardiac surgery: an analysis of the National Inpatient Sample.

The short-term impact of atrial fibrillation (AF) on cardiac surgery hospitalizations has been previously reported in cohorts of various sizes, but results have been variable. Using the 2005-2014 National Inpatient Sample, we identified all adult hospitalizations for cardiac surgery using the International Classification of Diseases, Ninth Revision, Clinical Modification as any procedure code and AF as any diagnosis code. We estimated the impact of AF on inpatient mortality, length of stay (LOS), and cost of hospitalization using survey-weighted, multivariable logistic, accelerated failure-time log-normal, and log-transformed linear regressions, respectively. Additionally, we exact-matched AF to non-AF hospitalizations on various confounders for the same outcomes. A total of 1,269,414 hospitalizations were noted for cardiac surgery during the study period. Coexistent AF was found in 44.9% of these hospitalizations. Overall mean age was 65.6 years, 40.9% were female, mean LOS was 11.6 days, and inpatient mortality was 4.5%. Stroke rate was lower in AF hospitalizations (1.8% vs 2.1%, p<0.001). Mortality was lower in the AF (3.9%) versus the non-AF (5%) group (exact-matched OR or emOR=0.48, 95% CI 0.29 to 0.80, p<0.001; 987 matched pairs, n=2423), with similar results after procedural stratification: isolated valve replacement/repair (emOR=0.38, p<0.001), isolated coronary artery bypass graft (CABG) (emOR=0.33, p<0.001), and CABG with valve replacement/repair (emOR=0.55, p<0.001). A 12% increase was seen in LOS in the AF subgroup (exact-matched time ratio=1.12, 95% CI 1.10 to 1.14, p<0.001) among hospitalizations which underwent valve replacement/repair with or without CABG. Hospitalizations for cardiac surgery which had coexistent AF were found to have lower inpatient mortality risk and stroke prevalence but higher LOS and hospitalization costs compared with hospitalizations without AF.

A Case of Hemothorax as Manifestation of Thoracic Endometrial Syndrome.

Thoracic endometriosis is a rare progression of a mostly benign disease of ectopic endometrial activity involving the pleura and lung. This is a case of a young female who presented with progressive shortness of breath and was found to have significant anemia. Further investigations showed a massive right-sided pleural effusion and ascites. Subsequent thoracentesis and pelvic diagnostic laparoscopy showed a hemorrhagic pleural effusion and ascites, along with dense pelvic adhesions. Pathology was consistent with endometriosis. Patient improved on leuprolide acetate and norethindrone. This case illustrates an important consideration in the differential of a reproductive-age female with new onset shortness of breath and anemia.

Fungal infections in hematopoietic stem-cell transplant patients: a review of epidemiology, diagnosis, and management.

The advent of bone marrow transplant has opened doors to a different approach and offered a new treatment modality for various hematopoietic stem-cell-related disorders. Since the first bone marrow transplant in 1957, there has been significant progress in managing patients who undergo bone marrow transplants. Plasma-cell disorders, lymphoproliferative disorders, and myelodysplastic syndrome are the most common indications for hematopoietic stem-cell transplant. Despite the advances, invasive fungal infections remain a significant cause of morbidity and mortality in this high-risk population. The overall incidence of invasive fungal infection in patients with hematopoietic stem-cell transplant is around 4%, but the mortality in patients with allogeneic stem-cell transplant is as high as 13% in one study. Type of stem-cell transplant, conditioning regimen, and development of graft-versus-host disease are some of the risk factors that impact the risk and outcomes in patients with invasive fungal infections. Aspergillus and candida remain the two most common organisms causing invasive fungal infections. Molecular diagnostic methods have replaced some traditional methods due to their simplicity of use and rapid turnaround time. Primary prophylaxis has undoubtedly shown to improve outcomes even though breakthrough infection rates remain high. The directed treatment has seen a significant shift from amphotericin B to itraconazole, voriconazole, and echinocandins, which have shown better efficacy and fewer adverse effects. In this comprehensive review, we aim to detail epidemiology, risk factors, diagnosis, and management, including prophylaxis, empiric and directed management of invasive fungal infections in patients with hematopoietic stem-cell transplant.

Spontaneous intercostal artery bleeding in a patient with alcohol-induced liver cirrhosis.

Spontaneous intercostal artery bleeding is a rare disease seen in cirrhosis and can present with hemodynamically significant blood loss anemia, hypotension, and shock. Transcatheter arterial embolization is an effective treatment for severe cases.

Radiation-Induced Lung Injury-Current Perspectives and Management.

Radiotherapy plays an important role in the treatment of localized primary malignancies involving the chest wall or intrathoracic malignancies. Secondary effects of radiotherapy on the lung result in radiation-induced lung disease. The phases of lung injury from radiation range from acute pneumonitis to chronic pulmonary fibrosis. Radiation pneumonitis is a clinical diagnosis based on the history of radiation, imaging findings, and the presence of classic symptoms after exclusion of infection, pulmonary embolism, heart failure, drug-induced pneumonitis, and progression of the primary tumor. Computed tomography (CT) is the preferred imaging modality as it provides a better picture of parenchymal changes. Lung biopsy is rarely required for the diagnosis. Treatment is necessary only for symptomatic patients. Mild symptoms can be treated with inhaled steroids while subacute to moderate symptoms with impaired lung function require oral corticosteroids. Patients who do not tolerate or are refractory to steroids can be considered for treatment with immunosuppressive agents such as azathioprine and cyclosporine. Improvements in radiation technique, as well as early diagnosis and appropriate treatment with high-dose steroids, will lead to lower rates of pneumonitis and an overall good prognosis.

Trends in Prevalence and Outcomes of Cannabis Use Among Chronic Obstructive Pulmonary Disease Hospitalizations: A Nationwide Population-Based Study 2005-2014.

Background: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality in the United States. Due to the ongoing legalization of cannabis, its acceptance, availability, and use in the in-patient population are on the rise. In this retrospective study, we investigated the association of cannabis use with important outcomes in COPD hospitalizations. Methods: The National Inpatient Sample (NIS) data were analyzed from 2005 to 2014. The primary outcome of interest was the trends and outcomes of cannabis use among COPD hospitalizations, including in-hospital mortality, pneumonia, sepsis, and respiratory failure. Results: We identified 6,073,862 hospitalizations, 18 years of age or older, with COPD using hospital discharge codes. Of these, 6,049,316 (99.6%) were without cannabis use, and 24,546 (0.4%) were admitted with cannabis use. The majority of COPD hospitalizations with cannabis use were aged 50-64 (60%). Cannabis use was associated with lower odds of in-hospital mortality (odds ratio [OR] 0.624 [95% confidence interval (CI) 0.407-0.958]; p=0.0309) and pneumonia (OR 0.882 [95% CI 0.806-0.964]; p=0.0059) among COPD hospitalizations. Cannabis use also had lower odds of sepsis (OR 0.749 [95% CI 0.523-1.071]; p=0.1127) and acute respiratory failure (OR 0.995 [95% CI 0.877-1.13]; p=0.9411), but it was not statistically significant. Conclusions: Among hospitalized patients with a diagnosis of COPD, cannabis users had statistically significant lower odds of in-hospital mortality and pneumonia compared to noncannabis users. The association between cannabis use and these favorable outcomes deserves further study to understand the interaction between cannabis use and COPD.

A Unique Case of Spontaneous Pneumomediastinum in a Patient With COVID-19 and Influenza Coinfection.

Spontaneous pneumomediastinum is reported in patients with coronavirus disease-2019 (COVID-19) and influenza infection independently, usually associated with noninvasive and mechanical ventilation. We report a case of spontaneous pneumomediastinum in a patient with COVID-19 and influenza coinfection. A 58-year-old male admitted with shortness of breath, diagnosed with COVID-19 and influenza infection. A computed tomography angiogram showed pneumomediastinum. He was treated conservatively with 15 L of oxygen, remdesivir, convalescent plasma, and oseltamivir. The case is being reported for its uniqueness since this is the first documented case of spontaneous pneumomediastinum in COVID-19 and influenza coinfection.

The Effects of Warfarin and Direct Oral Anticoagulants on Systemic Vascular Calcification: A Review.

Warfarin has been utilized for decades as an effective anticoagulant in patients with a history of strong risk factors for venous thromboembolism (VTE). Established adverse effects include bleeding, skin necrosis, teratogenicity during pregnancy, cholesterol embolization, and nephropathy. One of the lesser-known long-term side effects of warfarin is an increase in systemic arterial calcification. This is significant due to the association between vascular calcification and cardiovascular morbidity and mortality. Direct oral anticoagulants (DOACs) have gained prominence in recent years, as they require less frequent monitoring and have a superior side effect profile to warfarin, specifically in relation to major bleeding. The cost and lack of data for DOACs in some disease processes have precluded universal use. Within the last four years, retrospective cohort studies, observational studies, and randomized trials have shown, through different imaging modalities, that multiple DOACs are associated with slower progression of vascular calcification than warfarin. This review highlights the pathophysiology and mechanisms behind vascular calcification due to warfarin and compares the effect of warfarin and DOACs on systemic vasculature.

Clostridium Difficile and Noncirrhotic Hyperammonnemia in a Patient With COVID-19 Infection.

Clostridium difficile is a bacterial infection that usually presents with diarrhea and is mostly associated with previous antibiotics use. Patients with coronavirus disease 2019 (COVID-19) generally have respiratory symptoms but can also present with diarrhea. Noncirrhotic hyperammonemia is an infrequent presentation and is treated with lactulose. We report the case of a 40-year-old male who was admitted to our hospital with abdominal pain, diarrhea, shortness of breath, and confusion. During hospitalization, the patient tested positive for COVID-19 and C. difficile, and oral vancomycin was administered. His kidney functions improved, but he remained confused. His ammonia levels were elevated, and he was not treated with lactulose due to ongoing diarrhea secondary to C. difficile infection.

Diffuse alveolar hemorrhage associated with ustekinumab treatment.

PURPOSE: A case of diffuse alveolar hemorrhage (DAH) occurring as a reaction to ustekinumab therapy is reported. SUMMARY: After starting ustekinumab for treatment of psoriatric arthritis, a 46-year-old female presented with flu-like symptoms and cough with blood-tinged sputum that had begun 1 week previously. Her initial computed tomography scan of the chest demonstrated bilateral ground-glass opacities. On bronchoscopy, the bronchoalveolar lavage (BAL) return became bloodier from sample 1 to samples 2 and 3. Her BAL fluid was more than 90% hemosiderin-laden macrophages, a finding consistent with DAH. We ruled out infectious etiologies and other common vasculitis conditions that can cause DAH. A diagnosis of ustekinumab-induced DAH was made due to a temporal relationship between initiation of the drug and the patient's presentation and the absence of infection and other alternate diagnosis. Prior case reports including ustekinumab-induced pneumonitis, interstitial lung disease with a granulomatous component, and lupus syndrome have been reported, with this being the first case of DAH in a patient undergoing treatment of psoriatic arthritis. CONCLUSION: A 46-year-old woman developed DAH during ustekinumab treatment. Symptoms abated after drug discontinuation and supportive treament. Clinicians must remain mindful of this rare complication of ustekinumab use in order to avoid potential delays in appropriate DAH treatment.

Isolated Radial Vein Thrombosis: Upper Extremity Deep Vein Thrombosis in a Patient With COVID-19 Infection.

In general, upper extremity deep vein thrombosis (DVT) is less common than lower extremity DVT. Among upper extremity DVT cases, most of them are due to secondary causes like indwelling catheters, cancer, surgery, trauma or immobilization by plaster casts, pregnancy, oral contraceptives, and estrogen. Patients with coronavirus disease 2019 (COVID-19) infection are known to have coagulation dysfunction and a high incidence of DVT, mostly in the lower extremities; however, upper extremity DVT has been rarely reported. We present a rare case of upper extremity DVT in COVID-19 infection. A 56-year-old male with no significant past medical history was admitted with acute respiratory failure due to COVID-19 pneumonia. During hospitalization, he developed right upper extremity swelling, and an ultrasonogram showed right radial vein thrombosis. He was initially started on low molecular weight heparin (LMWH) and was discharged on apixaban. Patients with COVID-19 infection who develop DVT are recommended treatment with a direct oral anticoagulant (DOAC) for three months.

Pulmonary Hyalinizing Granuloma: A Rare Cause of a Benign Lung Mass.

Pulmonary hyalinizing granuloma (PHG) is a rare, benign lung disease of unknown etiology. It usually manifests as solitary and sometimes as multiple pulmonary nodules. It may have irregular margins, cavitation, or calcifications mimicking metastasis or primary lung neoplasm. It should be considered in the differential diagnosis of pulmonary nodules or masses. In this report, we present an unusual case of incidental slow-growing lung mass in a patient with 30 pack-year smoking history, construction-based occupation. The pleural-based calcified nodule in the left upper lobe gradually increased in size over ten years without any hilar or mediastinal lymphadenopathy. For an accurate diagnosis, PET-scan and histopathological analysis through wedge resection by video-assisted thoracoscopic surgery (VATS) were done. The biopsy findings were consistent with pulmonary hyalinizing granuloma, a rare benign cause of lung mass with an excellent long-term prognosis.

Disseminated Mycobacterium abscessus infection and native valve endocarditis.

Mycobacterium abscessus is a rapidly growing mycobacterium. It rarely causes disseminated infection or endocarditis. A 55-year-old male with a history of hepatitis C, liver cirrhosis, intravenous drug use (last use was four years ago), and chronic back pain presented with a three-week history of a right calf nodular lesion. He did not have a fever, chills, rash, dyspnea, or cough. Laboratory data showed mild leukocytosis. Computed tomography of the chest revealed bilateral cavitating nodules. Skin biopsy, sputum, and blood cultures grew Mycobacterium abscessus. Therapy with meropenem, tigecycline, and amikacin was initiated. He was re-admitted with worsening lower back pain. A lumbar magnetic resonance imaging showed destructive changes of L4 and L5 vertebral bodies concerning for osteomyelitis. Blood culture and bone biopsy grew Mycobacterium abscessus again. An echocardiogram was performed due to persistent bacteremia, which revealed large vegetation on the tricuspid valve and small vegetation on the mitral valve. Therapy was changed to eight weeks of amikacin, with cefoxitin and imipenem for twelve months based on drug susceptibility. Treatment of disseminated Mycobacterium abscessus is challenging due to antibiotic resistance. Typically, multidrug therapy is warranted with at least three active drugs. In severe valvular endocarditis, valve replacement may be required.