Evaluation of Amphotericin B Lipid Formulations for Treatment of Severe Coccidioidomycosis.

Patients with severe coccidioidomycosis infections are often treated with either amphotericin B lipid complex (ABLC) or liposomal amphotericin B (L-AmB). Outcome data with these agents in severe coccidioidomycosis cases are currently lacking. The purpose of this study is to evaluate the efficacy and toxicity of ABLC and L-AmB in treating severe coccidioidomycosis. A retrospective pre-post study design was employed. Chart reviews were completed from 1 January 2005 to 31 December 2014 for all patients who received lipid-based amphotericin B. Inclusion criteria included having a follow-up complement fixation (CF) titer or a treatment emergent adverse event (TEAE) prior to follow-up. Patients with meningeal involvement and pregnant patients were excluded. Treatment outcomes were assessed based on documented completion of therapy as well on symptoms, complement fixation titer, and changes to laboratory monitoring parameters. A total of 108 patients were identified, 69 of whom met the inclusion criteria. There were no statistical differences in demographics or disease burden in those that received ABLC and those that received L-AmB, except that those who received L-AmB were more likely to have previously diagnosed chronic kidney disease (nL-AmB = 4, 12.5% vs nABLC = 0, 0.0%; P = 0.042) and to have a lower creatinine clearance at the start of therapy (L-AmB = 79.6 mg/dl versus ABLC = 100.4 mg/dl; P = 0.008). Successful treatment was achieved in 27 (73.0%) of ABLC patients and 22 (68.8%) of L-AmB patients (P = 0.700). Amphotericin B was discontinued due to documented completion of therapy for 17 (45.9%) ABLC patients and 18 (56.3%) L-AmB patients (P = 0.553). Acute kidney injury (AKI) was the documented reason of treatment cessation for 10 (27.0%) ABLC and 1 (3.1%) L-AmB patient (P = 0.007). ABLC and L-AmB both appear to be equally efficacious in the treatment of severe coccidioidomycosis. L-AmB may have less renal toxicity than ABLC and may be the preferred agent in baseline renal impairment.

Perioperative Strokes Following Surgical Correction of Mitral Valves: A Systematic Review and Meta-Analysis.

OBJECTIVE: The primary aim of this meta-analysis was to quantify the impact of perioperative strokes on stroke-related mortality after open mitral valve (MV) procedures were performed. METHODS: An electronic search of the PubMed, Embase, and the Web of Science databases was performed to retrieve articles published up to December 2015, relevant to patients undergoing MV procedures. Data were extracted from the final list of 25 studies to calculate a summary OR for 30-day stroke-related mortality. RESULTS: The stroke rate in the total sample population was 1.62% (73/4,498). The 30-day all-cause mortality rate was 3.51% (158/4,498). The percentage of total deaths caused by stroke was 6.87%. The summary OR of stroke-related mortality following MV procedures was estimated to be 7.22 (95% CI 4.13-12.63, p < 0.0001). A subgroup analysis was done for studies involving concomitant MV surgery and coronary artery bypass grafting. The summary estimate of the subgroup showed an OR of 8.508 (95% CI 1.552-46.622, p = 0.0136). CONCLUSION: Perioperative strokes following open MV procedures may be associated with more than 7 times greater odds of 30-day stroke-related mortality. They appear to be more commonly occurring than what is reported by current literature, making further studies investigating possible mechanisms and preventive measures a priority.

Transcranial Doppler Monitoring in Carotid Endarterectomy: A Systematic Review and Meta-analysis.

OBJECTIVES: To evaluate the efficacy of intraoperative transcranial Doppler monitoring in predicting perioperative strokes after carotid endarterectomy (CEA). METHODS: An electronic search of PubMed, Embase, and Web of Science databases was conducted for studies on transcranial Doppler monitoring in CEA published from January 1970 through September 2015. All titles and abstracts were independently screened on the basis of predetermined inclusion criteria, which included randomized clinical trials and prospective or retrospective cohort reviews, patients who underwent CEA with intraoperative transcranial Doppler monitoring (either middle cerebral artery velocity [MCAV] or cerebral microembolic signals [MES]) and postoperative neurologic assessments up to 30 days after the surgery, and studies including an abstract, published in English on adult humans 18 years and older with a sample size of 50 or greater. RESULTS: A total of 25articles with a sample population of 4705 patients were analyzed. Among the study patients, 189 developed perioperative strokes. Transcranial Doppler monitoring (either MCAV or MES) showed specificity of 72.7% (95% confidence interval [CI], 61.2%-81.8%) and sensitivity of 56.1% (95% CI, 46.8%-65.0%) for predicting perioperative strokes. Intraoperative MCAV changes during CEA showed strong specificity of 84.1% (95% CI, 74.4%-90.6) and sensitivity of 49.7% (95% CI, 40.6%-58.8) for predicting perioperative strokes. CONCLUSIONS: Patients with perioperative strokes are 4 times more likely to have had transcranial Doppler changes (either MCAV or MES) during CEA compared to patients without strokes. Simultaneous MCAV and MES monitoring by transcranial Doppler sonography and combined intraoperative monitoring of transcranial Doppler sonography with somatosensory evoked potentials and electroencephalography during CEA to predict perioperative stroke could not be evaluated because of a lack of clinical studies combining these measures.

Paraneoplastic Hypereosinophilia in Poorly Differentiated Adenocarcinoma of the Lung.

It is well-documented that lung and bronchus cancers are the leading cause of cancer death in the United States in both male and female patients, with lung adenocarcinoma accounting for the highest prevalence of lung cancers. Significant eosinophilia in the setting of lung adenocarcinoma has been documented in a few reports, being described as a rare paraneoplastic syndrome. We report on an 81-year-old female with hypereosinophilia-associated lung adenocarcinoma. A chest film showed a right lung mass, which was not apparent on a chest film 1 year prior, in the setting of significant leukocytosis of 27.90 x 103/mm3 with eosinophilia of 6.40 x 103/mm3. A computed tomography (CT) chest, obtained during admission, demonstrated significant right lower lobe mass enlargement since the previous study completed 5 months prior, with new occlusion of bronchi and pulmonary vessels to the region of the mass. Our observations are consistent with prior reports showing that the presence of eosinophilia in lung cancers may indicate rapid disease progression.

Empathy Can Be Taught, and Patients Teach it Best.

Empathy toward patients is an essential skill for a physician to deliver the best care for any patient. Empathy also protects the physician from moral injury and decreases the chances for malpractice litigations. The current graduate medical education curriculum allows trainees to graduate without getting focused training to develop empathy as a core competency domain. The tools to measure empathy inherently lack validity. The accurate measure of the provider's empathy comes from the patient's perspectives of their experience and their feedback, which is rarely reaching the trainee. The hidden curriculum in residency programs gives mixed messages to trainees due to inadequate role modeling by attending physicians. This narrative style manuscript portrays a teachable moment at the bedside vividly. The teaching team together reflected upon the lack of empathy, took steps to resolve the issue. The attending demonstrated role modeling as an authentic and impactful technique to teach empathy. The conclusion includes a proposal to include the patient's real-time feedback to trainees as an essential domain under Graduate Medical Education core competencies of professionalism and patient care.

Bilateral pneumatoceles resulting in spontaneous bilateral pneumothoraces and secondary infection in a previously healthy man with COVID-19.

An acute COVID-19 infection can result in cystic lung changes that have a unique presentation and are inherently difficult to manage with or without preexisting conditions. Even though reportedly very few COVID-19 patients develop secondary bacterial infections due to unclear mechanisms, a postviral sequela with typical and atypical organisms can prolong the course of lung damage. The long-term effects of COVID-19 lung damage are still unclear, as the morbidity of the disease process is yet to be fully understood. This report presents a rare complication of COVID pneumonia with bilateral necrotizing pneumatoceles presenting with hemoptysis and bilateral pneumothoraces with positive sputum cultures for Enterobacter aerogenes and Pseudomonas aeruginosa. It highlights rare complications of COVID-19 requiring multiple hospital admissions and ongoing home oxygen therapy.

Concurrent Bilateral Central Retinal Artery Occlusion Secondary to Sickle Cell Crisis.

Vascular occlusive crisis with a concurrent vision loss on both eyes is one of the most devastating disability for sickle cell disease patients. Reportedly occlusive crisis in the eyes is usually temporary whereas if not appropriately managed can result in permanent vision loss. A carefully managed sickle cell crisis could prevent multiple disabilities including blindness and stroke. We report a case of a 24-year-old female with a history of sickle cell disease who had acute bilateral vision loss during a sickle crisis and recovered significantly with a timely emergent erythrocytapheresis.

Atraumatic Splenic Rupture in a Patient on Apixaban and Dual Antiplatelet Therapy.

Splenic rupture due to any cause is a life-threatening complication and commonly attributed to trauma. Atraumatic splenic rupture is very rarely reported, and the incidence is currently unknown. Anticoagulants and dual anti-platelet medication can increase the chances of a splenic rupture. Surgical removal of the spleen may be warranted to prevent a life-threatening bleeding. Early identification and intervention are required for most patients as only a few qualify for medical management.

Embolizing Massive Right Atrial Thrombus in a HIV-Infected Patient.

The risk of thromboembolism is increased when associated with the human immunodeficiency viral (HIV) infection. Various factors are involved in promoting thrombosis, and the presence of a patent foramen ovale augments the potential for a paradoxical embolism. We describe the case of a 56-year-old man receiving antiretroviral therapy with features of right heart failure and pulmonary embolism. Due to the high incidence of life-threatening thromboembolism in the HIV-infected group, the need for long-term anticoagulation has to be evaluated.

Giant Condylomata Acuminata of Buschke-Lowenstein Associated With Paraneoplastic Hypercalcemia.

Low-risk human papillomavirus types 6 and 11 can manifest as giant condylomata acuminata (GCA) of Buschke-Lowenstein. Up to 50% of GCA can slowly progress over years to fungating, invasive tumors. The malignant potential is attributed to unique immune evading abilities of the human papillomavirus. A 42-year-old male presented with pain and foul-smelling discharge from his genital warts. The histopathological examination of the mass showed invasive squamous cell carcinoma, and it was associated with paraneoplastic hypercalcemia. The timely removal of long-standing GCA in order to prevent a carcinomatous transition is a priority.

Unmasking a Case of Asymptomatic Charcot-Marie-Tooth Disease (CMT1A) With Vincristine.

Charcot-Marie-Tooth (CMT) disease is a hereditary demyelinating disease of the peripheral nervous system that results in sensory and motor dysfunction. CMT includes a spectrum of diseases with different types of mutations in the genes encoding myelin protein, resulting in a variety of dysfunctions in its life cycle. In CMT subtype 1A there is duplication mutation of peripheral myelin protein 22 gene on chromosome 17. Incomplete penetrance, gene-dosage effect, and variable expressivity can attribute to the asymptomatic nature of the disease in some subset of patients. Vincristine administration is contraindicated in patients who are alrea\dy diagnosed with CMT disease. We report a case of asymptomatic CMT disease unmasked only by the neurotoxic effects of vincristine. Genetic testing for a patient with a preexisting family background of inherited diseases before starting vincristine therapy can potentially prevent a disability.

Erythema Sweetobullosum: A Reactive Cutaneous Manifestation of Coccidioidomycosis.

Reactive cutaneous coccidioidal skin manifestations are commonly noticed during the early stage of coccidioidomycosis. These skin lesions are devoid of any active coccidioidal organism, and the immune trigger mechanisms are not elucidated. We describe 6 cases of unusual reactive cutaneous coccidioidal manifestation, characterized by painful vesiculobullous lesions known as erythema sweetobullosum. The biopsy of the lesions revealed neutrophilic dermatosis with inflammatory cells resulting in a cleft and elevation of the most superficial layer of the skin forming a bulla. The reactive cutaneous lesion is self-limited and requires no specific therapy.

Granulomatous Invasive Aspergillus flavus Infection Involving the Nasal Sinuses and Brain.

Invasive fungal infections are commonly associated with some form of immunosuppression. On the nasal epithelial surface, Aspergillus flavus, under favorable conditions, can aggressively breach multiple cell lines invading the local tissues. We present the case of a 35-year-old woman with granulomatous invasive Aspergillus flavus infection involving the nasal sinuses and the brain. Antifungal agents administered in the previous episodes contained the infection; however, the infected site evolved over time surrounded with calcified tissues in the left maxillary sinus. The current infection involved the other side of the maxillary sinus and extended to the orbital cavity eroding the parts of the skull and retro-orbital structures and was treated with a long course of isavuconazole therapy.

Perioperative neurologic complications during spinal fusion surgery: incidence and trends.

BACKGROUND CONTEXT: Perioperative neurologic complications after spine surgery may increase morbidity and health-care costs related to the procedure. PURPOSE: We estimate the national incidence of perioperative neurologic complications following anterior cervical discectomy and fusion (ACDF), posterior cervical fusion, and thoracolumbar fusion procedures using the Nationwide Inpatient Sample (NIS) data from 1999 to 2011. Additionally, we identify risk factors for developing perioperative neurologic complications and the effects of these injuries on quantifiable patient outcomes. STUDY DESIGN: A cross-sectional study was carried out. PATIENT SAMPLE: All patients included in the NIS databases from 1999 to 2011 comprised the sample. OUTCOME MEASURES: The primary outcome evaluated was the incidence of new neurologic deficits following elective spine surgery. Secondary outcomes evaluated include length of hospital stay, total hospital charges, hospital mortality rate, and discharge disposition. METHODS: A retrospective analysis of the NIS databases from the years 1999 to 2011 was conducted to identify the proportion of patients who underwent ACDFs, posterior cervical fusions, and thoracolumbar fusions who also developed perioperative neurologic complications. Statistical analyses were also conducted to identify statistically significant differences in demographics and outcomes between patients who did and did not develop perioperative neurologic complications. RESULTS: From 1999 to 2011, the total national incidence of perioperative neurologic deficits following elective ACDFs, posterior cervical fusions, and thoracolumbar fusions was 0.82%, which equates to a total of 15,066 patients who experienced these complications. The annual incidence rate of perioperative neurologic deficits has increased 54.41%, from 0.68% in the year 1999 to 1.05% in the year 2011. Additionally, the total number of procedures performed increased from 82,167 in 1999 to 186,353 in the year 2011. Perioperative neurologic deficits were associated with longer lengths of stay (9.68 days vs. 2.59 days; p<.001), higher total charges ($110,326.23 vs. $48,695.93; p<.001), and higher in-hospital mortality (2.84% vs. 0.13%; p<.001). CONCLUSIONS: The incidence rate of perioperative neurologic deficits associated with elective spine surgery documented in the NIS has increased over the time period from 1999 to 2011. The number of elective spine procedures performed has also increased over the same time period. Finally, outcomes data indicate that occurrence of perioperative neurologic complications is associated with increased rates of morbidity and mortality, as well as increased health-care use and cost. These trends indicate that the perioperative neurologic complications following spine surgery represent a growing problem in today's health-care system; further study is warranted to prevent and treat these complications to improve patient care and reduce health-care use and cost.

Diagnostic accuracy of somatosensory evoked potential and electroencephalography during carotid endarterectomy.

BACKGROUND AND PURPOSE: Perioperative stroke risk following carotid endarterectomy (CEA) is reported to be approximately 2-3%. The diagnostic accuracies of intraoperative EEG and SSEP monitoring during CEA have been studied separately. However, to date, the effectiveness of simultaneous EEG and SSEP monitoring during CEA has only been evaluated in small study populations. This study examined the diagnostic accuracy of combined EEG and SSEP monitoring in a large (N = 1165) patient population. METHODS: This study included 1165 patients who underwent CEA from 2000 to 2012 at the University of Pittsburgh Medical Center. The sensitivities, specificities, and diagnostic odds ratio of EEG and SSEP monitoring methods were examined separately and together. Receiver operating characteristic curves were plotted to assess sensitivity and specificity of single and combined Intraoperative monitoring (IONM) methods. RESULTS: Maximum sensitivity was obtained with multimodality monitoring with an IONM change in either EEG or SSEP of 50.00 (95% CI, 30.66-69.34). The specificity of simultaneous EEG and SSEP changes was 93.95 (95% CI, 92.28-95.35%). Maximum area under ROC curve obtained for IONM change in either EEG or SSEP was 0.660 (95% CI, 0.547-0.773, p-value 0.004). CONCLUSION: The diagnostic accuracy of multimodality IONM during CEA is higher than an approach using single modality IONM. Simultaneous EEG and SSEP monitoring improves the likelihood of detecting periprocedural strokes after CEA. Neuro protective therapies to prevent periprocedural strokes can be based on changes in SSEP and EEG during CEA.

Is Two Really Better Than One? Examining the Superiority of Dual Modality Neurophysiological Monitoring During Carotid Endarterectomy: A Meta-Analysis.

BACKGROUND: Periprocedural stroke after carotid endarterectomy increases long-term mortality. Intraoperative monitoring with electroencephalography (EEG) and somatosensory-evoked potentials (SSEPs) helps predict perioperative stroke risk. However, the sensitivity of each technique when used independently still remains low. The aim of this study is to determine whether multimodal monitoring leads to an increase in sensitivity and diagnostic accuracy. METHODS: Relevant literature was obtained through a search of Embase, PubMed, and Web of Science databases and data were extracted. Data from the University of Pittsburgh Medical Center hospital records for the 2000-2012 period were included. Pooled estimates of sensitivity, specificity, and diagnostic odds ratio were obtained for single and multimodality neurophysiologic monitoring. A McNemar test was used to evaluate for any statistically significant differences in the sensitivities and false-positive rates. RESULTS: The diagnostic odds ratio of dual modality monitoring was found to be 17.4. The specificity of concurrent EEG and SSEP changes in predicting perioperative strokes was calculated to be 96.8% (95% confidence interval 94.1%-98.3%). The sensitivity of combined monitoring with a change in either modality designated as significant was 58.9% (95% confidence interval 41.2%-74.7%). Multimodality monitoring with a change in either EEG or SSEP as the alarm criteria was 1.32 times more sensitive than EEG alone and 1.26 times more sensitive than SSEP alone. CONCLUSIONS: The odds of having a change in either EEG or SSEP are 17 times more in patients with perioperative strokes. Dual modality monitoring is more sensitive at predicting perioperative deficits than EEG or SSEP used independently.

A protocol for the emergency department management of acute undifferentiated febrile illness in India.

BACKGROUND: Fever is a common presenting complaint in the developing world, but there is a paucity of literature to guide investigation and treatment of the adult patient presenting with fever and no localizing symptoms. OBJECTIVE: The objective of this study was to devise a standardized protocol for the evaluation and treatment of febrile adult patients who have no localizing symptoms in order to reduce unnecessary testing and inappropriate antimicrobial use. After devising the protocol, a pilot study was performed to assess its feasibility in the emergency department. METHODS: A protocol was formulated for adult patients presenting with fever who had no clinical evidence of sepsis and no localizing symptoms to suggest the etiology of their fever. Investigations were based on duration of fever with no investigations indicated prior to day 3. Treatment was guided by results of investigations. A pilot study was performed after protocol implementation, wherein data were collected on successive adult patients presenting with fever. RESULTS: During the 6-week study period, 342 patients presented with fever, 209 of whom fit the parameters of the protocol, with 113 of these patients presenting on the 1st or 2nd day of fever. All patients experienced defervescence of fever, with ten patients being lost to follow-up. Of the patients presenting on day 1 or 2 of fever, 75.2% (85/113) defervesced without the need for testing; 53.1% (60/113) experienced defervescence without the need for antimicrobial therapy. CONCLUSION: Implementation of this rational, standardized protocol for the assessment and treatment of stable adult patients presenting with acute undifferentiated febrile illness can lead to reduced rates of testing and antimicrobial use. A prospective, controlled trial will be required to confirm these findings and to assess additional safety outcome measures.