Pulmonary sarcoidosis: A comprehensive review: Past to present.

Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph nodes. Worldwide it is estimated to affect 2-160/100,000 people and has a mortality rate over 5 years of approximately 7%. For sarcoidosis patients, the cause of death is due to sarcoid in 60% of the cases, of which up to 80% are from advanced cardiopulmonary failure (pulmonary hypertension and respiratory microbial infections) in all races except in Japan were greater than 70% of the sarcoidosis deaths are due to cardiac sarcoidosis. Scadding stages for pulmonary sarcoidosis associates with clinical outcomes. Stages I and II have radiographic remission in approximately 30%-80% of cases. Stage III only has a 10%-40% chance of resolution, while stage IV has no change of resolution. Up to 40% of pulmonary sarcoidosis patients progress to stage IV disease with lung parenchyma fibroplasia, bronchiectasis with hilar retraction and fibrocystic disease. These patients are at highest risk for the development of precapillary pulmonary hypertension, which may occur in up to 70% of these patients. Sarcoid patients with pre-capillary pulmonary hypertension can respond to targeted pulmonary arterial hypertension medications. Stage IV fibrocytic sarcoidosis with significant pulmonary physiologic impairment, >20% fibrosis on HRCT or pre-capillary pulmonary hypertension have the highest risk of mortality, which can be >40% at 5-years. First line treatment for patients who are symptomatic (cough and dyspnea) with parenchymal infiltrates and abnormal pulmonary function testing (PFT) is oral glucocorticoids, such as prednisone with a typical starting dose of 20-40 mg daily for 2 weeks to 2 months. Prednisone can be tapered over 6-18 months if symptoms, spirometry, PFTs, and radiographs improve. Prolonged prednisone may be required to stabilize disease. Patients requiring prolonged prednisone ≥10 mg/day or those with adverse effects due to glucocorticoids may be prescribed second and third line treatements. Second and third line treatments include immunosuppressive agents (e.g., methotrexate and azathioprine) and anti-tumor necrosis factor (TNF) medication; respectively. Effective treatments for advanced fibrocystic pulmonary disease are being explored. Despite different treatments, relapse rates range from 13% to 75% depending on the stage of sarcoid, number of organs involved, socioeconomic status, and geography. CONCLUSION: The mortality rate for sarcoidosis over a 5 year follow up is approximately 7%. Unfortunately, 10%-40% of patients with sarcoidosis develop progressive pulmonary disease, and >60% of deaths resulting from sarcoidosis are due to advance cardiopulmonary disease. Oral glucocorticoids are the first line treatment, while methotrexate and azathioprine are considered second and anti-TNF agents are third line treatments that are used solely or as glucocorticoid sparing agents for symptomatic extrapulmonary or pulmonary sarcoidosis with infiltrates on chest radiographs and abnormal PFT. Relapse rates have ranged from 13% to 75% depending on the population studied.

Adherence to blood product transfusion guidelines-An observational study of the current transfusion practice in a medical intensive care unit.

BACKGROUND: Blood transfusions though life-saving are not entirely benign. They are the most overused procedure in the hospital and have been under scrutiny by the 'Choosing Wisely campaign'. The strict adoption of restrictive transfusion guidelines could improve patient outcomes while reducing cost. OBJECTIVES: In this study, we evaluate adherence to restrictive transfusion guidelines, along with hospital mortality and length of stay (LOS) in transfusion events with a pre-transfusion haemoglobin (Hb) ≥7 g/dl. Additionally, we evaluated associated costs accrued due to unnecessary transfusions. METHODS: We conducted a retrospective observational study in a 64-bed medical intensive care unit (MICU) of an academic medical centre involving all adult patients (N = 957) requiring packed red blood cell transfusion between January 2015 and December 2015. RESULTS: In total, 3140 units were transfused with a mean pre-transfusion Hb of 6.75 ± 0.86 g/dl. Nine hundred forty-four (30%) transfusion events occurred with a pre-transfusion Hb ≥7 g/dl, and 385 (12.3%) of these occurred in patients without hypotension, tachycardia, use of vasopressors, or coronary artery disease. Forgoing them could have led to a savings of approximately 0.3 million dollars. Transfusion events with pre-transfusion Hb ≥7 g/dl were associated with an increased mortality in patients with acute blood loss (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.11-3.88; p = 0.02) and LOS in patients with chronic blood loss (ß1 .8.26, 95% CI 4.09-12.43; p < 0.01). CONCLUSION: A subset of anaemic patients in the MICU still receive red blood cell transfusions against restrictive guidelines offering hospitals the potential for effective intervention that has both economic and clinical implications.

A Unique Case of Combined Nodular and Tracheobronchial Amyloidosis.

Amyloidosis is a heterogeneous group of diseases characterized by the extracellular deposition of misfolded proteins that can affect either systemically or locally confined to one system. Pulmonary amyloidosis is rare and can be classified into three forms according to the anatomic site of involvement: nodular pulmonary amyloidosis, tracheobronchial amyloidosis and diffuse alveolar-septal amyloidosis. The former two usually represent localized amyloid disease and the latter represents systemic disease. Typically lung parenchymal and tracheobronchial amyloidosis do not present together in localized forms of pulmonary amyloidosis. Here we report a unique case of localized pulmonary immunoglobulin light-chain amyloidosis, manifested as both parenchymal nodules and tracheobronchial amyloid deposition.

Resolution of a posttraumatic pancreatic pseudocyst with octreotide acetate in a pediatric patient.

A pancreatic pseudocyst is a complication of abdominal trauma in pediatric patients. Octreotide acetate is an effective adjunct therapy used in combination with traditional surgical approaches. We describe a 19-month-old boy with a pancreatic pseudocyst secondary to blunt abdominal trauma who was successfully managed with octreotide acetate in combination with percutaneous drainage and the placement of a pancreatic stent. Octreotide acetate 1 µg/kg/hour was administered as a continuous intravenous infusion for 24 hours, followed by 2.5 µg/kg/dose every 12 hours subcutaneously for 11 days. The patient was discharged after the pseudocyst had resolved and oral feeding was restored. He had no recurrence of the pseudocyst. The published literature regarding octreotide acetate therapy for pediatric pancreatic pseudocysts is limited. Previously reported cases demonstrated successful resolution of pancreatic pseudocysts with varying doses of intravenous and subcutaneous octreotide acetate within 23-30 days; however, with our patient's regimen, along with surgical interventions, the pseudocyst resolved within 11 days. In addition, our patient's regimen involved higher doses of octreotide acetate given more frequently than those reported in the literature. This case report illustrates that use of higher octreotide acetate dosages may be a potential adjunct therapy to surgical interventions for the management of pancreatic pseudocysts in children.

Stem cell based delivery of IFN-beta reduces relapses in experimental autoimmune encephalomyelitis.

Interferon-beta (IFN-beta), an approved treatment of multiple sclerosis (MS), produces only partial clinical responses. IFN-beta therapy has been limited by its short serum half-life and limited ability to cross the blood brain barrier. We have developed a means of delivering the IFN-beta gene both systemically and into the central nervous system (CNS) using bone marrow stem cells (BMSCs) as a vehicle and examined the therapeutic efficacy of this approach in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. A retroviral expression vector (pLXSN-IFNbeta) was used to stably transfect virus producer PA317 cells to generate retrovirus containing the IFN-beta gene which then was used to transduce BMSCs. IFN-beta engineered BMSCs were transplanted (i.v.) into mice that then were immunized with proteolipoprotein (PLP) to initiate EAE. IFN-beta-engineered BMSCs transplanted mice showed a significant inhibition of EAE onset, and the overall clinical severity was less compared to control groups. IFN-beta delivery strongly reduced infiltration of mononuclear cells possibly by inhibiting cell adhesion molecules. Reduced demyelination and increased remyelination were also observed in the IFN-beta treated group. Furthermore, inhibition of the pro-inflammatory cytokines TNF-alpha, IFN-gamma and IL-12 and enhanced expression of the anti-inflammatory cytokines IL-10, IL-4 and TGF-beta was observed in CNS tissue. In addition, mice receiving IFN-beta had reduced apoptosis and increases in growth promoting factors including BDNF, CNTF, PDGF and VEGF. These results suggest that BMSCs can be used as vehicles to deliver the IFN-beta into the CNS. This is a potentially novel therapeutic approach which might be used in MS and other diseases of the CNS in which drug access is limited.