Impact of Age on Outcomes in Hospitalized Patients with Hereditary Hemorrhagic Telangiectasia.

BACKGROUND: There is little published literature regarding the impact of age on outcomes amongst hospitalized HHT (hereditary hemorrhagic telangiectasia) patients. METHODS: The Nationwide Inpatient Sample (NIS) was used to obtain data on all hospital discharges occurring in HHT patients from 2000 to 2012. The association between admission age and HHT-related complications and outcomes were studied. RESULTS: 10293 hospitalizations in HHT patients from 2000 to 2012 were included. Patients > 50 accounted for 77% of all admissions with 30% of admissions occurring in the 51-65 age group. Bleeding related complications were the most frequent (62.7%, n = 6455 hospitalizations), followed by cardiovascular (41%, n = 4216), neurological (12.4%, n = 1276), and hepatobiliary (6.4%, n = 660) complications. Patients older than 50 accounted for 83% of bleeding events, 90% of cardiovascular events, 58% of neurologic events, and 81% of hepatobiliary events. The vast majority (83%) of medical and surgical procedures were performed in those older than 50 years of age. Older patients also experienced higher rates of death. CONCLUSION: Aging has significant adverse impacts on rates of hospitalization, complications, and outcomes amongst HHT patients in the United States. Except for neurologic complications, the vast majority of this disease burden is borne by patients older than 50 years.

Intravenous Bevacizumab for Refractory Hereditary Hemorrhagic Telangiectasia-Related Epistaxis and Gastrointestinal Bleeding.

OBJECTIVE: To present a multiyear clinical experience with intravenous bevacizumab for the management of severe gastrointestinal bleeding and/or epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). PATIENTS AND METHODS: All patients treated with intravenous bevacizumab for severe hereditary hemorrhagic telangiectasia-related bleeding from June 1, 2013, through January 31, 2017, were included in this report. Severity of epistaxis (determined using the Epistaxis Severity Score questionnaire); hemoglobin, iron, and ferritin levels; and quality of life data were collected serially in all patients. RESULTS: Intravenous bevacizumab was administered to 34 patients using a standardized treatment protocol. Anemia was primarily related to severe epistaxis (n=15, 44%), severe gastrointestinal bleeding (n=4, 12%), or both (n=15, 44%), with a median baseline hemoglobin level of 9.1 g/dL (range, 8.3-10.5 gm/dL; to convert to mmol/L, multiply by 0.62). Red blood cell (RBC) transfusions had been administered to 28 patients (82%). Of these, 16 patients (47%) were RBC transfusion dependent and had received a median of 75 RBC transfusions (range, 4->500 RBC units) before bevacizumab initiation. The median length of follow-up was 17.6 months from the beginning of bevacizumab treatment (range, 3-42.5 months). There was a significant reduction in epistaxis severity scores (P<.001) and RBC transfusion requirements (P=.007) after completion of the initial bevacizumab treatment cycle. New-onset or worsened hypertension was noted in 4 patients, with 1 patient experiencing hypertensive urgency with a temporary decline in renal function. CONCLUSION: Intravenous bevacizumab is an effective treatment option for patients with severe anemia related to epistaxis and/or gastrointestinal bleeding. Further studies are needed to establish a dose-response relationship as well as clinical, genetic, and biomarker predictors of response.

Saddle vs Nonsaddle Pulmonary Embolism: Clinical Presentation, Hemodynamics, Management, and Outcomes.

OBJECTIVE: To understand the clinical significance, hemodynamic presentation, management, and outcomes of patients presenting with saddle pulmonary embolism (PE). METHODS: All patients with saddle PE diagnosed at Mayo Clinic in Rochester, Minnesota, from January 1, 1999, through December 31, 2014, were included in this study. These patients were age and simplified Pulmonary Embolism Severity Index (sPESI) matched (1:1) to a nonsaddle PE cohort. Both groups were then classified into massive, submassive, and low-risk PE based on established criteria and compared for clinical presentation, management, and outcomes. RESULTS: A total of 187 consecutive patients with saddle PE were identified. The saddle PE group presented more frequently with massive PE (31% vs 20%) and submassive PE (49% vs 32%), whereas low-risk PE was more common in the nonsaddle PE group (48% vs 20%). Systemic thrombolysis was used more frequently in the saddle PE group on admission (10% vs 4%; P=.04) and later during hospitalization (3.2% vs 0%; P=.03). Late major adverse events were similar in both groups except for mechanical ventilation (6% in saddle PE vs 1% in nonsaddle PE; P=.02). Overall in-hospital mortality did not differ between the 2 groups (4.3% in saddle PE vs 5.4% in nonsaddle PE; P=.81). CONCLUSION: Although patients with saddle PE presented with higher rates of hemodynamic compromise and need for thrombolysis and mechanical ventilation, we found no difference in short-term outcomes compared with an age- and severity-matched nonsaddle PE cohort. Overall, in-hospital mortality was low in both groups.

Multifocal micronodular pneumocyte hyperplasia (MMPH) in a patient with tuberous sclerosis-evidence for long term stability.

Multifocal micronodular pneumocyte hyperplasia (MMPH) is rare entity seen mostly in patients with the tuberous sclerosis complex (TSC). We present the case of a 50 year old woman with TSC (confirmed TSC2 mutation) found to have multiple ground glass opacities with an upper lobe predominance on a screening chest CT. No abnormalities were detected in other viscera. A thoracoscopic lung biopsy obtained from right upper lobe confirmed the diagnosis of MMPH. There were no lesions suggestive of lymphangioleiomyomatosis (LAM) either on the chest CT or lung biopsy. A repeat CT chest obtained on follow up 9 years after initial diagnosis continued to show stability of all MMPH ground glass lesions. This case highlights the distinct patterns of lung involvement in TSC, with MMPH having a benign and stable nature as compared to LAM which is often relentlessly progressive with associated lung function decline.

Effect of Center Volume on Outcomes in Hospitalized Patients With Hereditary Hemorrhagic Telangiectasia.

OBJECTIVE: To determine whether hospitalized patients with hereditary hemorrhagic telangiectasia (HHT) had better outcomes at high-volume treatment centers (HVCs). PATIENTS AND METHODS: The Nationwide Inpatient Sample (2000-2011) was used to identify HHT-related hospitalizations. Hospitals were classified based on quartiles of annual HHT discharge volume. The 75th percentile cutoff value (third quartile) was used to classify hospitals as low-volume centers (1-7 HHT discharges per year) or as HVCs (≥8 discharges per year. Demographic features, complication rates, and outcomes were compared between the 2 groups. RESULTS: We identified 9440 hospital discharges in patients with HHT. Of these patients, 6856 (72.6%) were admitted to low-volume centers and 2584 (27.4%) to HVCs. The former were more likely to be of white race, older, and with higher income levels (P<.001 for each). The HVCs had higher rates of anemia, epistaxis, congestive heart failure, pulmonary hypertension, and cerebral and pulmonary arteriovenous malformations and lower rates of ischemic stroke and myocardial infarction. After adjusting for baseline differences in a multivariate model, patients treated at HVCs were more likely to be discharged home (odds ratio [OR]=1.35; 95% CI, 1.21-1.52; P<.001) and less likely to be discharged to short-term rehabilitation facilities (OR=0.45; 95% CI, 0.31-0.64; P<.001). Patients treated at HVCs also had a significantly lower risk of in-hospital mortality (OR=0.51; 95% CI, 0.34-0.74; P<.001). CONCLUSION: Patients with HHT hospitalized at HVCs had better outcomes, with lower in-hospital mortality and higher home discharge rates. These findings strongly support ongoing efforts to expand access to HHT centers of excellence in the United States and worldwide.

Isolated Intravascular Large B-cell Lymphoma Presenting with Diffuse Ground Glass Pulmonary Infiltrates.

A case of 44-year-old man with dyspnea and CT chest demonstrated bilateral infiltration. Patient was failed to improve with antibiotics and steroid. Finally, video-assisted thoracic surgery-guided lung biopsy was performed and surprisingly revealed intravascular large B cell lymphoma. The patient was subsequently started on chemotherapy with considerable clinical improvement. At the time of last follow-up (4 years from diagnosis); there was no clinical or radiologic evidence of tumor recurrence.

Phenytoin induced Steven-Johnson syndrome and bronchiolitis obliterans - case report and review of literature.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are both rare but serious idiosyncratic drug reactions characterized by diffuse muco-epidermoid injury and high mortality. Keratinocytes in both skin and mucous membranes (including eyes, mouth and genitalia) are injured resulting in a diffuse maculopapular rash, blistering lesions and epithelial detachment with minimal force (Nikolsky's sign). SJS is typically diagnosed when less than 10% of the skin surface is involved and the term TEN is used in cases with more than 30% involvement. Respiratory involvement in SJS-TEN is common with 30-50% of cases demonstrating respiratory epithelial sloughing with severe short and long term complications. Patients who survive SJS-TEN are often left with impaired respiratory function and bronchiolitis obliterans. Cases of bronchiolitis obliterans with SJS/TEN have been very rarely reported. We report a case of phenytoin induced SJS/TEN followed by severe bronchiolitis obliterans in an adult patient. The presentation, pathophysiology and management of SJS/TEN related bronchiolitis obliterans is also reviewed.

Fatal right ventricular failure and pulmonary hypertension after protamine administration during cardiac transplantation.

Protamine sulfate is the only Food and Drug administration approved medication for reversal of intraoperative heparin-induced anticoagulation during cardiac and vascular surgeries. One of the rare side effects of protamine sulfate is an idiosyncratic reaction resulting in acute pulmonary hypertension (APH) and right ventricular (RV) failure occurring after protamine administration. These reactions are rare but catastrophic with high mortality. A 36-year-old female with severe congestive heart failure was undergoing cardiac transplant surgery. After successful implantation of the donor heart, the patient was weaned off cardiopulmonary bypass. Protamine was then administered to reverse the heparin anticoagulation. She immediately developed APH and RV failure immediately after protamine infusion. The patient required immediate administration of inotropic agents, nitric oxide (NO), and subsequently required a number of mechanical support devices including an RV assist device (RVAD) and ultimately full veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite heroic efforts, the patient developed refractory multi-organ failure in the Intensive Care Unit and died after family requested discontinuation of resuscitative efforts. This case probably represents the first reported occurrence of fatal protamine-induced APH and ventricular failure in the setting of cardiac transplantation surgery. A number of interventions including inhaled NO, systemic vasopressors, RVAD, and ultimately VA-ECMO failed to reverse the situation, and the patient died of multi-organ failure.

Occult pulmonary lymphangitic carcinomatosis presenting as 'chronic cough' with a normal HRCT chest.

A diagnosis of 'chronic cough' (CC) requires the exclusion of sinister pulmonary pathology, including infection and malignancy. We present a patient with a 3 month history of CC who had an extensive workup including a normal high resolution computed tomography of the chest (HRCT) 6 weeks prior to consultation at our center. He subsequently developed constitutional symptoms including weight loss and loss of appetite 5 weeks after initial consultation. A repeat HRCT chest and a subsequent whole body PET scan found that he had developed extensive pulmonary lymphangitic carcinomatosis (PLC) from a colon primary. Treatment of the colon cancer resulted in significant decrease in metastatic disease burden and cough resolution. PLC is a very rare cause of 'chronic cough' and incipient/occult PLC presenting with chronic cough and a normal initial HRCT chest has not been previously reported.

Lung adenocarcinoma presenting with isolated 'chronic cough' of 3 years duration-a cautionary tale.

Chronic cough that is dry, non-productive and without constitutional symptoms is often thought to have a non-malignant etiology such as asthma, post-nasal drip or gastroesophageal reflux disease (GERD). We present a case of a patient with a 3 year history of 'chronic cough' that was dry, non-productive cough and without any constitutional symptoms. Initial chest x-ray (CXR) done 3 years ago showed some streaky atelectasis in the right middle lobe along with some volume loss on that side. Another CXR performed one and half years later showed progression to a complete right middle lobe collapse. She ultimately presented to our facility a year later with stable CXR findings, but persistent cough. A chest CT scan was suspicious for a right lower lobe mass. A PET scan subsequently confirmed a hypermetabolic right hilar mass causing extrinsic compression of the bronchus intermedius. She ultimately required a complete right pneumonectomy with partial pericardiectomy and had complete resolution of her cough. This case highlights the fact that 'chronic cough' should always be thoroughly investigated and should remain a diagnosis of exclusion until all sinister pathologies have been ruled out.