The Ominous Aspergillus With Cancer of Blood Vessels: A Case of Invasive Aspergillosis and Epithelioid Angiosarcoma of the Lung.

Invasive aspergillosis occurs in the setting of risk factors such as severe or prolonged neutropenia, defects in cell-mediated immunity, and receipt of immunosuppressive therapy, particularly in patients with graft-versus-host disease (GVHD). Pulmonary epithelioid angiosarcomas (EASs) are rare malignant vascular tumors that are aggressive, frequently metastatic, and associated with a poor prognosis. We describe these two rare conditions occurring concurrently.

Octreotide as a novel agent for the management of bronchorrhea in mechanically ventilated patients: A case series and review of literature.

Excessive bronchial secretions pose a challenge in mechanically-ventilated patients and may prolong the time to extubation, increasing the risk for pneumonia. Octreotide, a somatostatin analog, has been used to decrease bronchial secretions especially for the symptomatic management of patients with lung cancer. We describe three patients in the form of a case series and discuss effect of octretotide on bronchial secretions and management of bronchorrhea in the intensive care unit. Similar to reports of its utilization in palliative care in patients with lung cancer, we observed a clinically significant decrease in the rate of bronchial secretions.

Clinical Outcomes With the Use of Prophylactic Versus Therapeutic Anticoagulation in Coronavirus Disease 2019.

OBJECTIVES: To determine the impact of anticoagulation on inhospital mortality among coronavirus disease 2019-positive patients with the a priori hypothesis that there would be a lower risk of inhospital mortality with use of preemptive therapeutic over prophylactic dose enoxaparin or heparin. DESIGN SETTING: Retrospective cohort study from April 1, 2020, to April 25, 2020. The date of final follow-up was June 12, 2020 Two large, acute-care hospitals in Western Connecticut. PATIENTS: Five hundred and one inpatients were identified after discharge as 18 years or older and positive for severe acute respiratory syndrome coronavirus 2. The final sample size included 374 patients after applying exclusion criteria. Demographic variables were collected via hospital billing inquiries, whereas the clinical variables were abstracted from patients' medical records. EXPOSURE: Preemptive enoxaparin or heparin at a therapeutic or prophylactic dose. MAIN RESULTS: When comparing treatments through multivariable analysis, risk of inhospital mortality was 2.3 times greater in patients receiving preemptive therapeutic anticoagulation (95% CI = 1.0-4.9; p = 0.04). Additionally, the average treatment effects were higher (ß = 0.11, p = 0.01) in the therapeutic group. CONCLUSIONS: An increase in inhospital mortality was observed among patients on preemptive therapeutic anticoagulation. Thus, in the management of coronavirus disease 2019 and its complications, we recommend further research and cautious use of preemptive therapeutic over prophylactic anticoagulation.

The impact of video laryngoscopy use during urgent endotracheal intubation in the critically ill.

BACKGROUND: The video laryngoscope (VL) has been shown to improve laryngoscopic views and first-attempt success rates in elective operating room and simulated tracheal intubations compared with the direct laryngoscope (DL). However, there are limited data on the effectiveness of the VL compared with the DL in urgent endotracheal intubations (UEIs) in the critically ill. We assessed the effectiveness of using a VL as the primary intubating device during UEI in critically ill patients when performed by less experienced operators. METHODS: We compared success rates of UEIs performed by Pulmonary and Critical Care Medicine (PCCM) fellows in the medical intensive care unit and medical or surgical wards. A cohort of PCCM fellows using GlideScope VL as the primary intubating device was compared with a historical cohort of PCCM fellows using a traditional Macintosh or Miller blade DL. The primary measured outcome was first-attempt intubation success rate. Secondary outcomes included total number of attempts required for successful tracheal intubation, rate of esophageal intubation, need for supervising attending intervention, duration of intubation sequence, and incidence of hypoxemia and hypotension. RESULTS: There were 138 UEIs, with 78 using a VL and 50 using a DL as the primary intubating device. The rate of first-attempt success was superior with the VL as compared with the DL (91% vs 68%, P < 0.01). The rate of intubations requiring ≥3 attempts (4% vs 20%, P < 0.01), unintended esophageal intubations (0% vs 14%, P < 0.01), and the average number of attempts required for successful tracheal intubation (1.2 ± 0.56 vs 1.7 ± 1.1, P < 0.01) all improved significantly with use of the VL compared with the DL. CONCLUSIONS: UEI using a VL as the primary device improved intubation success and decreased complications compared with a DL when PCCM fellows were the primary operators. These data suggest that the VL should be used as the primary device when urgent intubations are performed by less experienced operators.

A program to improve the quality of emergency endotracheal intubation.

OBJECTIVE: To assess the results of a quality improvement (QI) project designed to improve safety of emergency endotracheal intubation (EEI). DESIGN: Single center prospective observational. SETTING: 16-bed intensive care unit. PARTICIPANTS: Nine pulmonary/critical care fellows. INTERVENTIONS: For 3 years, EEI performed by the medical intensive care unit team were analyzed to identify interventions that would improve quality of the procedure. By segmental process analysis, the procedure of EEI was subjected to iterative change. Major components of process improvement were development of a combined team approach, a mandatory checklist, use of crew resource management (CRM) tactics, and postevent debriefing. Quality analysis and improvement included training of fellows using scenario-based training (SBT) with computerized patient simulator (CPS) to improve mechanical skills of intubation and team leadership. Fellows received 15 sessions of SBT with CPS using a combined checklist and team approach before assuming team leadership position during real-life EEI. MEASUREMENTS: For a 10-month period, fellows carried digital voice recorders to EEI; which, when combined with recording of continuous oximetry and BP monitoring were used to assess the quality of EEI. MAIN RESULTS: 128 EEI were performed of which 101 had full data recorded. Complications were 14% severe hypoxemia (<80% saturation), 6% severe hypotension (SBP<70 mm Hg), 1% death, 20% difficult EEI (≥ 3 attempts), 11% esophageal intubations, 2% aspiration, and 1% dental injury; 62% EEI were successfully achieved on first attempt, 11% required >3 attempts. CONCLUSIONS: EEI may be performed by pulmonary/critical medicine (PCCM) fellows with safety comparable to that described in other studies on EEI. Important parts of the program included the use of formal iterative QI approach, the use of intensive SBT with CPS, basic CRM, a comprehensive checklist, and a combined team approach. A key benefit of the program was to make the process of EEI fully transparent for ongoing quality and safety improvement.

Competency in chest radiography. A comparison of medical students, residents, and fellows.

BACKGROUND: Accurate interpretation of chest radiographs (CXR) is essential as clinical decisions depend on readings. OBJECTIVE: We sought to evaluate CXR interpretation ability at different levels of training and to determine factors associated with successful interpretation. DESIGN: Ten CXR were selected from the teaching file of the internal medicine (IM) department. Participants were asked to record the most important diagnosis, their certainty in that diagnosis, interest in a pulmonary career and adequacy of CXR training. Two investigators independently scored each CXR on a scale of 0 to 2. PARTICIPANTS: Participants (n=145) from a single teaching hospital were third year medical students (MS) (n=25), IM interns (n=44), IM residents (n=45), fellows from the divisions of cardiology and pulmonary/critical care (n=16), and radiology residents (n=15). RESULTS: The median overall score was 11 of 20. An increased level of training was associated with overall score (MS 8, intern 10, IM resident 13, fellow 15, radiology resident 18, P<.001). Overall certainty was significantly correlated with overall score (r=.613, P<.001). Internal medicine interns and residents interested in a pulmonary career scored 14 of 20 while those not interested scored 11 (P=.027). Pneumothorax, misplaced central line, and pneumoperitoneum were diagnosed correctly 9%, 26%, and 46% of the time, respectively. Only 20 of 131 (15%) participants felt their CXR training sufficient. CONCLUSION: We identified factors associated with successful CXR interpretation, including level of training, field of training, interest in a pulmonary career and overall certainty. Although interpretation improved with training, important diagnoses were missed.

MUC-1 mucin protein expression in B-cell lymphomas.

We have recently shown that MUC1, mapped to the chromosomal band 1q21, is rearranged or amplified in 15% of B-cell lymphomas and that rearrangement led to over-expression of MUC-1 mucin in a case of diffuse large B-cell lymphoma (DLBCL). To determine the incidence of MUC-1 mucin expression and its clinical significance in B-cell lymphomas, we investigated a panel of 113 cases by immunohistochemistry (IHC). MUC-1 mucin expression was detected in the majority of cases (92.9%), with moderate to high levels noted in 50.4% of all histologic subsets comprising DLBCL (82 cases), follicular lymphoma (FL) (15 cases), FL with transformation to DLBCL (4 cases), and other B-cell lymphomas (12 cases). No statistically significant correlation was found between MUC-1 mucin expression and MUC1 genomic status (amplification/rearrangement) evaluated by Southern blot analysis, and 1q21 abnormality by karyotypic analysis. For all cases, MUC-1 mucin expression correlated with a previous history of lymphoma (p=0.003).

Application of tissue microarray technology to the study of non-Hodgkin's and Hodgkin's lymphoma.

The immunohistochemical analysis of lymphoid neoplasms has led to refined classification schemes based on the profile of antigen expression and correlation with morphological, cytogenetic, molecular, and clinical features. Tissue microarrays (TMAs) are a powerful tool to rapidly characterize the phenotypic profile of a large number of samples. We show that this technique can be readily applied to the study of lymphoma by examining the expression profile of a series of 193 B-cell non-Hodgkin's lymphomas (NHLs) and 29 Hodgkin's lymphomas (HLs) using immunohistochemistry and in situ hybridization (ISH). The NHL cases were studied for the expression of commonly used markers-including CD3, CD5, CD10, CD20, CD23, CD30, CD43, Bcl-2, and cyclin D1 by immunohistochemical staining of TMAs-and these results were compared with whole sections (WS) of the same cases. We found a high degree of correlation between the results achieved with TMAs or WS (86% to 100% of cases). P53 and MIB-1 staining were studied, and the results were similar to that reported in the literature. HL cases were stained for CD20, CD30, CD15 (LeuM1), and latent membrane protein 1 expression, and ISH was performed using probes for EBER-1 and-2 transcripts. The results from HL cases on TMA sections matched exactly with those of WS. We correlated cytogenetic results with immunohistochemical stains and morphology in cases of mantle cell lymphoma [t(11;14)(q13;q32)] and follicular lymphoma [t(14;18)(q32;q24)]. This extensive expression profile of B-cell NHLs and HL tissues discloses the ability of TMAs to rapidly screen a large series of cases and represents the first report of method validation for this technique in the study of lymphoma.

Spectral karyotyping identifies new rearrangements, translocations, and clinical associations in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL), a histologically well-defined subset of non-Hodgkin lymphoma, is clinically and genetically heterogenous. By G-banding, most cases showed complex hyperdiploid karyotypes and diverse cytogenetic abnormalities that included recurring and nonrecurring translocations, deletions, duplications, and marker chromosomes. While G-banding provided valuable leads to identification of specific rearrangements that enabled gene discovery and clinical correlations, many aberrations remained uncharacterized because of their complexity. The molecular cytogenetic technique spectral karyotyping (SKY), on the other hand, enables complete characterization of all aberrations in a tumor cell karyotype and, hence, precise quantitation of chromosome instability. We report here, for the first time, SKY analysis of a panel of 46 DLBCL cases previously analyzed by G-banding, ascertained at the Memorial Sloan-Kettering Cancer Center. This analysis provided a cytogenetic profile of DLBCL that was characterized by a higher level of instability, qualitatively as well as quantitatively, compared with G-banding. Thus, 551 breakpoints were detected by SKY, in contrast to the 295 by G-banding. Several new recurring breakpoints, translocations, and regions of gain and loss were identified, which included 13 breakpoints not previously identified by G-banding, 10 breakpoints that were underrepresented by G-banding, and 4 previously unrecognized translocations: der(14)t(3;14)(q21;q32), t(1;13)(p32;q14), t(1;7)(q21;q22), and der(6)t(6;8)(q11;q11). We identified new clinical associations involving recurring breakpoints detected by SKY. These studies emphasize the value of SKY analysis for redefinition of chromosomal instability in DLBCL to enhance gene discovery as well as clinical correlation analysis.

Primary follicular lymphoma of the gastrointestinal tract: a clinical and pathologic study of 26 cases.

Although the gastrointestinal tract represents the most common site of extranodal lymphoma, primary follicular lymphoma of the gastrointestinal tract is an uncommon and poorly defined disease. We report the clinical and pathologic features of 26 patients with primary gastrointestinal follicular lymphoma. Ten of 26 patients (38.5%) were stage IIE, and 16 patients (61.5%) were stage IE. Of the 26 patients, 13 were female and 13 were male. The age range was 26-81 years (median 54.5 years). Abdominal pain was the most common presenting symptom, seen in 12 of 24 patients (50%). Nodularity of the mucosal surface was the most common endoscopic finding, seen in 10 of 14 patients (71.4%). The majority of cases (22 of 26, 84.6%) involved small bowel, four involved colorectum alone, and two involved the ileocecal valve. Within the small bowel the duodenum was the most commonly involved site (10 cases). Transmural involvement by follicular lymphoma was identified in 11 of the 16 patients who underwent surgical resection; five showed involvement of mucosa and submucosa only. The most common histologic grade was grade 1. Thirteen of 26 cases were grade 1, ten grade 2, and three grade 3. Twenty-one of 26 cases showed a predominantly follicular growth pattern, four mixed follicular and diffuse, and one predominantly diffuse. All cases were positive for CD20 and BCL2 and negative for CD3, CD5, CD23, CD43, and cyclin D1. Twenty-four of 26 were positive for CD10. Four of four cases showed cytogenetic or molecular genetic evidence of t(14;18). Initial treatment modalities included surgery plus chemotherapy (nine cases), surgery alone (seven cases), chemotherapy alone (four cases), observation alone (four cases), and chemotherapy and abdominal radiation (one case). One case presented with rectal polyps and was treated with polypectomy. A complete response was observed in 15 of 22 cases that received treatment, and of the 15 cases, five recurred 27-60 months after the initial diagnosis. Recurrence and progression were associated with histologic transformation to diffuse large cell lymphoma in one case. No significant correlation was identified between treatment response and various clinical and pathologic features. Overall, none of the 26 patients died of lymphoma. One patient died of a concomitant pancreatic carcinoma. Of the remaining 25 patients, 14 were disease free and 11 were alive with disease at a mean follow-up of 43 months. The estimated 5-year disease-free survival was 62%, and median disease-free survival was 69 months. The estimated 5-year relapse-free survival was 54%, and the median relapse-free survival was 63 months.