Satish Maharaj

Necrotizing Pseudomonas aeruginosa Community-Acquired Pneumonia: A Case Report and Review of the Literature

Lung cavities are not typically associated with community-acquired pneumonia (CAP). CAP due to P. aeruginosa is rare and even less commonly causes necrotizing pneumonia. We report a case of P. aeruginosa CAP that progressed to necrotizing pneumonia and was eventually fatal. Procalcitonin (PCT) has been well investigated in guiding antibiotic therapy (especially CAP) in adults. In this case, PCT at presentation and sequentially was negative. We discuss this caveat and present hypotheses as to the sensitivity and specificity of PCT and C-reactive protein (CRP) in these patients. To better characterize P. aeruginosa CAP, we undertook a review of cases indexed in PubMed from 2001 to 2016 (n = 9). The data reveal that risk factors for P. aeruginosa CAP include smoking, alcohol use, obstructive lung disease, sinusitis, and hot tub use. The route of infection for P. aeruginosa CAP remains unknown. One of the most interesting findings on reviewing cases was that P. aeruginosa CAP involves the right upper lobe in the vast majority. We suggest that when physicians in the community see patients with distinctly upper lobe necrotizing or cavitary pneumonia, they should consider P. aeruginosa in their differential diagnosis. Further studies are needed to clarify route of infection, role of PCT and CRP, and optimal therapy including drug and duration.

Severe beta blocker and calcium channel blocker overdose: Role of high dose insulin

&NA; A 54‐year‐old female presented after taking an overdose of an unknown amount of hydrochlorothiazide, doxazocin, atenolol and amlodipine. She was initially refractory to treatment with conventional therapy (intravenous fluids, activated charcoal, glucagon 5 mg followed with glucagon drip, calcium gluconate 10%, and atropine). Furthermore, insulin at 4 U/kg was not effective in improving her hemodynamics. Shortly after high dose insulin was achieved with 10 U/kg, there was dramatic improvement in hemodynamics resulting in three of five vasopressors being weaned off in 8 h. She was subsequently off all vasopressors after six additional hours. The role of high dose insulin has been documented in prior cases, however it is generally recommended after other conventional therapies have failed. However, there are other reports that suggest it as initial therapy. Our patient failed conventional therapies and responded well only with maximum dose of insulin. Physicians should consider high dose insulin early in severe beta blocker or calcium channel blocker overdose for improvement in hemodynamics. This leads to early discontinuation of vasopressors. It is important that emergency physicians be aware of the beneficial effects of high dose insulin when initiated early as opposed to waiting for conventional therapy to fail; as these patients often present first to the emergency department. Early initiation in the emergency department can be beneficial in these patients.

Increased risk of arterial thromboembolic events with combination lenalidomide/dexamethasone therapy for multiple myeloma

ABSTRACT Introduction: Cancer associated thrombosis is a leading cause of morbidity and mortality. Research and guidelines have focused on venous thromboembolic events (VTE). Within the past decade, combination lenalidomide and dexamethasone has become a standard of therapy for multiple myeloma and is now widely used. In these patients, the risk of arterial thromboembolic events (ATE) has not been addressed to the same extent as VTE. Areas discussed: Presented is a targeted review of published data on ATE in MM patients on combination lenalidomide/dexamethasone therapy. Incidence, clinical presentations, prognosis, mechanisms and thromboprophylaxis are discussed. A framework for approaching ATE/VTE in these patients is suggested. Expert commentary: There is an increased incidence of ATE in this population, primarily cerebrovascular and cardiovascular events. ATE is associated with poorer prognosis and its prevention must be an important goal of management. It is suggested that on initiating treatment, a combined VTE/ATE risk assessment should be performed and thromboprophylaxis initiated for a minimum of 6 months. As newer immunomodulatory therapies are developed, thromboembolic risk must be assessed early on. Further studies are needed to determine the optimal strategy to reducing both VTE and ATE in this population.

Anti-PF4/heparin antibodies are increased in hospitalized patients with bacterial sepsis

Heparin-induced thrombocytopenia (HIT) is caused by antibodies targeting platelet factor 4 (PF4)/heparin complexes. The immune response leading to HIT remains perplexing with many paradoxes. Unlike other drug induced reactions, anti-PF4/heparin antibody generation does not follow the classic immunologic response. Research in murine models suggests that that there is close interplay among infection, PF4 and the immune system. We hypothesized there would be a relatively higher prevalence of anti-PF4/heparin antibodies in patients hospitalized for sepsis. We retrospectively examined anti-PF4/heparin antibody testing in 200 such patients. This included patients who had sepsis with bacteremia (n = 57), sepsis with fungemia (n = 7) and sepsis without bacteremia or fungemia (n = 136). For comparison, data from 50 patients without sepsis during the same time period was used. Results confirmed that patients hospitalized with sepsis have higher anti-PF4/heparin antibody levels. The groups of patients having sepsis with bacteremia, and sepsis without bacteremia, had significantly higher OD than the control group without sepsis (p < 0.05). There was no significant difference between Gram negative and Gram positive bacteremia and antibody levels. This suggests that bacterial cell wall components of both classes have similar antigenicity. Interestingly, patients who had sepsis with fungemia had much lower antibody levels compared to those with sepsis and bacteremia, and sepsis without bacteremia or fungemia. Despite the small sample size for fungemia, this difference trended strongly towards statistical significance (p = 0.05). It would be interesting to investigate this further in a larger study or using in vitro studies. In summary, there is an increased prevalence of anti-PF4/heparin antibodies in patients hospitalized with bacterial but not fungal sepsis. These results indicate that bacterial infection has a role to play in preimmunization leading to anti-PF4/heparin antibody generation.

Coexistent Ipsilateral Internal Carotid Artery Occlusion and Cerebral Venous Thrombosis in Hepatitis C

A 58-year-old male, known to have hepatitis C virus (HCV), presented with intermittent headaches and left-sided sensorimotor symptoms. There were no focal neurological deficits on examination. Electrocardiogram was unremarkable. Computed tomography angiography head and neck displayed extracranial right internal carotid artery occlusion. Magnetic resonance imaging showed right cortical vein thrombosis, with hemorrhagic infarction. Echocardiography with bubble study was unremarkable. Hypercoagulable workup was significant for protein S deficiency. He was treated with warfarin for 6 months. Repeat protein S levels remained low 9 months later. The coexistence of arterial and venous thrombotic events gives rise to a limited differential. In this case, it may be related to chronic HCV infection. The underlying pathogenesis is not clear; however, it is possible the patient had chronic high-grade internal carotid artery stenosis, which occluded leading to his presenting symptoms. The cortical vein thrombosis is likely an incidental finding here. The extent by which HCV contributed to the cerebral thrombosis and carotid artery occlusion in our case is not clear; however, the hypercoagulable and atherosclerotic properties of the virus cannot be disregarded. The virus can promote carotid atherosclerosis and cerebral venous thrombosis as well as other venous and arterial thromboembolic events. Furthermore, HCV is associated with impaired venous flow and procoagulant properties, which can fuel a hypercoagulable state. Also of note cirrhosis is associated with protein S deficiency. We recommend considering an underlying hypercoagulable state including both arterial and venous thrombosis in HCV infection.

Pilot study on the occurrence of multiple cancers following cancer-related therapy at the University of Florida, Jacksonville (2011–2016)

New primary cancers can occur in patients with a previous cancer. Among the risk factors, therapies such as chemotherapy, radiotherapy, and hormonal therapy have been associated with the development of neoplasms. Second cancers most commonly develop 5–10 years after the initial tumor. We observe the implications of cancer-related therapy in the development of a new tumor. We looked at 602 patients who had their first cancer diagnosed in 2011 and calculated the number of different primary cancers between 2011 and 2016 for each patient. Twenty-four patients had a second cancer within 5 years from the first diagnosis and there were no patients with a third cancer. There was no statically significant difference in the rates of second cancers after exposure to chemotherapy, radiotherapy, hormonal therapy, or any combination of these (p=0.738). Of the second cancers reported after 2011, renal, uterine, cervical, and lung cancers were the most frequently reported. Additionally, there was no statically significant difference among the rates of second cancers in men versus women (p=0.467), as well as among whites versus blacks (p=0.318). We conclude that while new primaries can occur after one cancer, there was no increased risk after exposure to different cancer-related therapies. With increased focus on the primary disease, there is a higher likelihood of missing another primary lesion. This is important as the practical implications of managing multiple primaries are rarely discussed.

Dynamic right ventricular outflow tract obstruction from a pedunculated cardiac metastasis

A 48-year-old African–American female presented to the Emergency Department with a complaint of chest discomfort and dyspnea. The patient was known to have squamous cell carcinoma of the bladder diagnosed 3 months prior, with invasion into the muscularis propria, staged as T2NxMx. On auscultation, there was a soft systolic murmur. Electrocardiography showed that sinus tachycardia and cardiac biomarkers were within normal limits. CT angiography (CTA) done in the Emergency Room excluded pulmonary emboli. Transthoracic echocardiography revealed normal cardiac function with preserved ejection fraction. However, the right ventricle was enlarged with an echodense round mass in the distal RVOT (arrow, Fig. 1a, b). The mass measured 2.2 × 1.9 cm (Fig. 1c) and was pedunculated with independent motion (see supplemental video) leading to turbulent flow in the RVOT. The rest of the examination was positive only for a small circumferential pericardial effusion. 18FDG PET scanning strongly suggested that this was a metastatic lesion. There was intense 18FDG uptake centered in the RVOT (Fig. 1d) with extension proximally and distally and SUV of 12.8. Unfortunately the patient died 3 months later with confirmed widespread metastatic disease from aggressive carcinoma of the bladder. Metastatic cardiac masses are typically from mediastinal or thoracic primary neoplasms or melanoma [1]. Metastases disseminate to the heart via three main routes: lymphatic, hematogenous, and direct or transvenous. The most frequent carcinomas implicated are breast and lung, with infradiaphragmatic tumors far less common [2]. Malignant melanoma, lymphoma, leukemia, and sarcoma usually spread hematogenously. Extracardiac tumors may also reach the atria and even the chambers of the heart by transvenous extension. To note, intraluminal growth of renal cell carcinoma through the renal vein into the vena cava and right atrium occurs in 1% of these tumors [2, 3]. There are only a handful of cases reported with cardiac metastasis from urothelial carcinoma [4]. Furthermore, metastases also usually arise from the intraventricular or septal myocardium or involve the valvular apparatus. This case is unique in that the tumor was pedunculated and mobile in the RVOT. The “tethered ball” morphology resulted in symptomatic obliteration of the RVOT. RVOT pedunculated metastasis is extremely rare, but, as this case demonstrates can lead to dynamic obstruction. It should be considered in the differential diagnosis of dyspnea or chest discomfort in the patient with cancer, and echocardiography should be done with particular attention to the RVOT on parasternal long axis and subcostal short axis views as demonstrated.

DKA-induced Brugada phenocopy mimicking STEMI

Case presentation A 47-year-old Caucasian woman with type 1 diabetes presented with epigastric pain and vomiting. She had not been adherent with her diet and insulin therapy for the past 3 weeks. She never had a personal or family history of arrhythmia-related symptoms, ventricular tachycardia or fibrillation (VT/VF) or premature sudden cardiac death (SCD). Examination revealed dry mucosa, tachycardia and epigastric tenderness to palpation. Her ECG showed ST elevations (V1–V3) with associated T wave inversions (figure 1A). A baseline ECG 1 year ago had no abnormalities. Serial troponin I and T were negative, but Creatinine Kinase MB (CKMB) was elevated. Her biochemistry test showed sodium of 118 mM, potassium of 6.7 mM, bicarbonate of 4 mM, anion gap of 40, glucose of 985 mM and beta hydroxyl-butyrate of >45.0 mg/dL. Cardiac catheterisation revealed normal anatomy with all vessels widely patent; left ventricular end diastolic pressure (LVEDP) was 1 mm Hg. With treatment, diabetic ketoacidosis (DKA) resolved after 8 hours and repeat ECG showed all changes had resolved (figure 1B). She was monitored on telemetry without any VT/VF episodes. Serial ECGs were done with resolution of changes. She had no positive studies for inducible VT. The rest of her admission was uneventful. Figure 1 (A) ECG on presentation. (B) ECG 8 hours after admission. Question Which of the following is the best next step in managing this patient? Quinidine therapy. Implantable cardioverter-defibrillator (ICD) placement. SCN5A gene mutation testing. Observation without therapy.

Sarcoidosis presenting with facial swelling (Heerfordt syndrome)

Sarcoidosis is one of the “great masqueraders” of medicine and can present with atypical facial swelling. Imaging and biopsy confirm the diagnosis.

Coexistent Breast Cancer and Essential Thrombocythemia: How We Addressed the Therapeutic Challenges

Essential thrombocythemia (ET) occurring with breast cancer is uncommon; the therapeutic approach varies and poses a challenge. A 65-year-old female presented to us after being diagnosed with hormone positive, HER2-negative infiltrating ductal carcinoma. She had a platelet count of 600 thou/cu mm. Her JAK2 mutation was positive. Bone marrow biopsy showed increased megakaryocytes. She was diagnosed with ET in the setting of breast cancer. She underwent breast conservation surgery after which aspirin was resumed. Anticipating thrombocytopenia during chemotherapy and given the absence of data combining hydroxyurea with standard chemotherapy used for breast cancer, we felt it prudent to delay cytoreductive therapy for her ET until after completion of breast cancer treatment. Her average platelet count during chemotherapy was 480 thou/cu mm with the lowest being 377 thou/cu mm. Her platelet count remained at goal between 300 and 350 thou/cu mm after four months of hydroxyurea.