Severe Monkeypox in Hospitalized Patients - United States, August 10-October 10, 2022.

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.§ Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox¶ during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy†† in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.§§ Engaging all persons with HIV in sustained care remains a critical public health priority.

Whole lung lavage: Treating pulmonary alveolar proteinosis at the time of COVID pandemic.

Pulmonary alveolar proteinosis (PAP) is a rare syndrome due to increased production or decreased clearance of surfactant in alveoli and terminal bronchi that cause hypoxemic respiratory insufficiency. Here we present a patient with PAP whose disease was exacerbated by superimposed COVID-19 pneumonia. He underwent whole lung lavage (WLL). Evaluation of the viral count of the first and the last lavage of the left lung showed viral load in the alveolar space dropped by approximately 10-folds, however the magnitude of the viral load was substantial in both lavage samples. Whole pulmonary lavage may be used as a treatment option on patients with PAP even when the disease is exacerbated by COVID-19 pneumonia.

Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.

Broken and forgotten: A case of unintentionally retained foreign object.

Central venous catheter have become ubiquitous with greater than 15 million catheter days/year in the intensive care setting alone. However, the procedure carries with it several immediate and other delayed complications that can result in significant morbidity, mortality, and increased healthcare cost. We report a rare case of significantly delayed complications associated with intravascular loss of guide wire during central venous catheter placement and its impact on patient's long term management. The case highlights not only the importance of proper technique and safety precaution in performing an increasingly common procedure, but also the need for timely identification and rectification of medical errors, especially in the context of improved physician-patient communication.

Effectiveness of an Advanced Critical Care Echocardiography Course.

BACKGROUND: Advanced critical care echocardiography (CCE) involves comprehensive assessment of cardiac structure and function for frontline critical care applications. This study reports the effectiveness of a 3-day course in advanced CCE. METHODS: We studied the outcome of 5 consecutive advanced CCE courses delivered between 2013 and 2017. A total number of 239 learners were studied. The course included didactic lectures, image interpretation sessions, and hands-on training with normal individuals as models. Training domains included left ventricular structure and function, right ventricular structure and function, valve function using comprehensive 2-dimensional imaging, and Doppler-based measurements for cardiac pressures and flows. Measurements of course outcome included pre- and postcourse assessment of knowledge, image acquisition, and image interpretation skills. Learners rotated between hands-on training and interpretation sessions. The teacher-to-learner ratio was 1:3 during hands-on training. Interpretation sessions consisted of review of normal and abnormal echocardiographic videos with interactive small groups. Learners completed a video-based knowledge assessment examination before and after completion of the course. Hands-on image acquisition skills were tested at the completion of the course during all the years. For years 2016 and 2017, a precourse hands-on skill test was also performed. RESULTS: There was a statistically significant improvement in knowledge and image interpretation skills in the cohort of 239 learners over 5 years of study period. There was improvement in image acquisition skills over the 2-year period when it was measured pre- and postcourse. CONCLUSIONS: A 3-day course on advanced CCE resulted in improvement knowledge/image interpretation and hands-on image acquisition skills. Clinical Implications: Advanced CCE has assumed an important place in hemodynamic monitoring of critically ill patients. A course of similar design may facilitate training of frontline clinicians in advanced CCE.

Effectiveness of a Transesophageal Echocardiography Course.

BACKGROUND: Transesophageal echocardiography has important applications for the management of the critically ill patient. There is a need to develop effective training programs for the critical care community in acquiring skill at critical care transesophageal echocardiography. OBJECTIVE: We studied the effectiveness of a 1-day simulation-based course that focused on the acquisition of skill in the performance of critical care transesophageal echocardiography. METHODS: Learners received training in image acquisition with a transesophageal simulator and training in image interpretation in small group sessions. Skill at image acquisition and image interpretation was assessed at the beginning and at the completion of the course. RESULTS: There were 27 learners who attended the course. Pre and post knowledge scores were 55 (19; mean [SD]) and 88 (9; P < .0005), respectively. Pre and post image acquisition scores were 3.6 (3.7) and 9.9 (0.3; P < .0001), respectively. CONCLUSIONS: A 1-day course in critical care transesophageal echocardiography that combined case-based image interpretation with image acquisition training using a simulator improved technical skills and knowledge base.

Bronchoscopic lung cryobiopsy: An Indian association for bronchology position statement.

BACKGROUND: Bronchoscopic lung cryobiopsy (BLC) is a novel technique for obtaining lung tissue for the diagnosis of diffuse parenchymal lung diseases. The procedure is performed using several different variations of technique, resulting in an inconsistent diagnostic yield and a variable risk of complications. There is an unmet need for standardization of the technical aspects of BLC. METHODOLOGY: This is a position statement framed by a group comprising experts from the fields of pulmonary medicine, thoracic surgery, pathology, and radiology under the aegis of the Indian Association for Bronchology. Sixteen questions on various technical aspects of BLC were framed. A literature search was conducted using PubMed and EMBASE databases. The expert group discussed the available evidence relevant to each question through e-mail and a face-to-face meeting, and arrived at a consensus. RESULTS: The experts agreed that patients should be carefully selected for BLC after weighing the risks and benefits of the procedure. Where appropriate, consideration should be given to perform alternate procedures such as conventional transbronchial biopsy or subject the patient directly to a surgical lung biopsy. The procedure is best performed after placement of an artificial airway under sedation/general anesthesia. Fluoroscopic guidance and occlusion balloon should be utilized for positioning the cryoprobe to reduce the risk of pneumothorax and bleeding, respectively. At least four tissue specimens (with at least two of adequate size, i.e., ≥5 mm) should be obtained during the procedure from different lobes or different segments of a lobe. The histopathological findings of BLC should be interpreted by an experienced pulmonary pathologist. The final diagnosis should be made after a multidisciplinary discussion. Finally, there is a need for structured training for performing BLC. CONCLUSION: This position statement is an attempt to provide practical recommendations for the performance of BLC in DPLDs.

NUT (Nuclear Protein in Testis) Carcinoma: A Report of Two Cases With Different Histopathologic Features.

NUT (nuclear protein in testis) carcinoma (NC) is an aggressive carcinoma characterized by rearrangements of the NUT gene on chromosome 15q14. Histologically, it is a poorly differentiated carcinoma composed of monotonous, medium-sized, round cells with scant amphophilic or eosinophilic cytoplasm. Foci of abrupt keratinization are often seen. In this report, we compare the morphology of 2 cases of NC. The first case shows characteristic features of uniform, round epithelioid cells admixed with foci of abrupt keratinization. The second case demonstrates nests of epithelioid-polygonal cells that appear to be loosely cribriform within a mucoid stroma. Although considered rare, the actual incidence of NC may be underestimated, as it is likely that many go undiagnosed because the morphology deviates from what is typical. Our report demonstrates that NC should always be considered in any case of an undifferentiated carcinoma and should not be excluded if typical histologic and immunohistochemical features of squamous differentiation are lacking.

Fatal Progressive Membranous Obliterative Bronchitis: A Sequela of Influenza?

Occlusion of the bronchial orifices by tissue-like structures is an uncommonly reported finding: it has been referred to as bronchial webs, bronchial synechiae, vanishing bronchus syndrome, or membranous obliterative bronchitis. It differs from bronchiolitis obliterans, a well-described clinical entity that involves smaller airways not visualized on bronchoscopy. Although initially only recognized as a congenital condition, later reports have described it in situations where chronic inflammation results in the irritation of the airways. Here we report a case of a woman with postinfectious bronchiectasis who developed membranous occlusion of multiple subsegmental bronchi, resulting in progressive airflow obstruction and postobstructive collapse of involved lung parenchyma. This process eventually caused her demise. It the first report of membranous occlusion of the bronchi in an adult who does not have cystic fibrosis or a history of lung transplantation. Clinicians should be aware of this entity, and further research could help illuminate its pathogenesis and management.

Rapid progression of pulmonary blastomycosis in an untreated patient of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is associated with a state of immunosuppression characterized by hypogammaglobulinemia as well as B and T lymphocyte dysfunction. Though opportunistic infections are common in CLL patients, particularly after treatment, reports of infections by endemic dimorphic fungi are very few. Here we report a case of pulmonary blastomycosis in a CLL patient who initially presented with an indolent pulmonary mass lesion. The pulmonary lesions progressed rapidly over a two-week period. The diagnosis was established by transbronchial lung biopsy. He was treated with Amphotericin B lipid complex followed by oral itraconazole and recovered uneventfully. This case illustrates the importance of a timely diagnosis and treatment. The presentation of blastomycosis in immunocompromised patients, diagnosis, and treatment are discussed.

Finding an alternative diagnosis does not justify increased use of CT-pulmonary angiography.

BACKGROUND: The increased use of computed tomography pulmonary angiography (CTPA) is often justified by finding alternative diagnoses explaining patients' symptoms. However, this has not been rigorously examined. METHODS: We retrospectively reviewed CTPA done at our center over an eleven year period (2000 - 2010) in patients with suspected pulmonary embolus (PE). We then reviewed in detail the medical records of a representative sample of patients in three index years - 2000, 2005 and 2008. We determined whether CTPA revealed pulmonary pathology other than PE that was not readily identifiable from the patient's history, physical examination and prior chest X-ray. We also assessed whether the use of pre-test probability guided diagnostic strategy for PE. RESULTS: A total of 12,640 CTPA were performed at our center from year 2000 to 2010. The number of CTPA performed increased from 84 in 2000 to 2287 in 2010, a 27 fold increase. Only 7.6 percent of all CTPA and 3.2 percent of avoidable CTPAs (low or intermediate pre-test probability and negative D-dimer) revealed previously unknown findings of any clinical significance. When we compared 2008 to 2000 and 2005, more CTPAs were performed in younger patients (mean age (years) for 2000: 67, 2005: 63, and 2008: 60, (p=0.004, one-way ANOVA)). Patients were less acutely ill with fewer risk factors for PE. Assessment of pre-test probability of PE and D-dimer measurement were rarely used to select appropriate patients for CTPA (pre-test probability of PE documented in chart (% total) in year 2000: 4.1%, 2005: 1.6%, 2008: 3.1%). CONCLUSIONS: Our data do not support the argument that increased CTPA use is justified by finding an alternative pulmonary pathology that could explain patients' symptoms. CTPA is being increasingly used as the first and only test for suspected PE.

Correlation of a scintigraphic pulmonary perfusion index with hemodynamic parameters in patients with pulmonary arterial hypertension.

PURPOSE: To determine whether the perfusion index (PI) can be used as a noninvasive measure to diagnose and predict the severity of disease in patients with pulmonary arterial hypertension (PAH). MATERIALS AND METHODS: Twenty-two patients were included in this retrospective investigation: 9 controls and 13 patients with PAH. Controls had no evidence of PAH [mean pulmonary arterial pressure (MPAP) ≤25 mm Hg and pulmonary capillary wedge pressure ≤18 mm Hg]. The study patients had PAH (MPAP ≥25 mm Hg and pulmonary capillary wedge pressure ≤18 mm Hg) and no diagnosis of pulmonary embolism. Due to the retrospective nature of the study, the PI was calculated from the posterior perfusion image of a ventilation perfusion scan. The PI was computed as the sum of differences versus control for the 9 deciles above background. Receiver operating characteristic curve analysis was used to compare PI with other parameters for predicting PAH. RESULTS: Linear correlations of PI were found to be significant with the following parameters: pulmonary vascular resistance (r=0.81, P=0.00009), total pulmonary vascular resistance (MPAP/cardiac output) (r=0.80, P=0.00013), pulmonary artery systolic pressure (r=0.73, P=0.00018), MPAP (r=0.72, P=0.00022), pulmonary diastolic pressure (r=0.53, P=0.01), and right atrial pressure (r=0.50, P=0.03). Using logistic regression, the PI was significant in separating patients with PAH from controls (χ²=5.6, P=0.02). CONCLUSION: The data suggest that PI can be used for the noninvasive diagnosis and measurement of severity of PAH.

Diagnosis and management bronchopleural fistula.

The diagnosis and management of bronchopleural fistula (BPF) remain a major therapeutic challenge for clinicians. It is associated with significant morbidity and mortality. Diagnosis and localisation of BPF is sometimes difficult and may require multiple imaging and bronchoscopies. Successful management of a fistula is combined with treatment of the associated empyema cavity. The first step, therefore, should be control of active infection and adequate drainage of the hemithorax. When deemed required, definitive surgical repair should be accomplished expeditiously, minimising the number of procedures performed. In cases of a small fistula or where the surgical risk is high, various bronchoscopic methods have been used to close the fistula. When treatment is protracted, secondary complications are more likely and survival is adversely affected. In this article, approaches to the diagnosis and treatment of BPF are discussed, with particular emphasis on bronchoscopic management options.

The role of computed tomography bronchography in the management of bronchopleural fistulas.

The management of complex bronchopleural fistulas (BPFs) remains a major diagnostic and therapeutic challenge to all chest physicians. Successful management of a fistula revolves around treatment of the associated empyema cavity first. Definitive repair should be accomplished expeditiously to minimize the number of procedures performed. When treatment is protracted, secondary complications are more likely to develop and survival is adversely affected. Diagnosis and localization of a BPF is therefore paramount; however, it is sometimes difficult and may require multiple imaging studies and bronchoscopies. Herein, we describe our experience with computed tomography bronchography as a new technique for diagnosis and localization of difficult BPF. In addition, other modalities for diagnosis and medical management are discussed along with a relevant review of the literature.

Critical care aspects of malaria.

Malaria remains a major health problem in much of Asia and Africa. A steady number of cases of imported malaria are also seen in many countries of the developed world. Plasmodium falciparum malaria and to some extent malaria caused by other species of Plasmodium can lead to many complications such as acute respiratory distress syndrome (ARDS), cerebral malaria, acute renal failure, severe anemia, thrombocytopenia, and bleeding complications. About 10% of patients with severe malaria die, usually as a result of multiorgan dysfunction. Critical care physicians should be aware of the complications and management of severe malaria. There has been significant progress in the understanding of pathogenesis of severe malaria over the last decade. Effective management of severe malaria includes early suspicion, prompt diagnosis, early institution of appropriate antimalarial chemotherapy, and supportive care, preferably in an intensive care unit. In this article, we review the different manifestations of severe malaria as relevant to critical care physicians and discuss the principles of laboratory diagnosis and management.