ß-Lactams plus doxycycline versus azithromycin for treatment of severe community-acquired pneumonia in critically ill patients.

OBJECTIVES: Community-acquired pneumonia (CAP) is a significant source of hospital admissions and mortality. Atypical organisms are implicated in up to 40% of cases of CAP diagnoses. We studied the difference in outcomes of severe CAP patients treated with doxycycline versus azithromycin in addition to ß-lactam therapy. PATIENTS AND METHODS: This was a prospective observational cohort study from March 2020 to July 2022 in a medical ICU (MICU) of an academic quaternary medical center. Adults ≥18 years admitted to the MICU receiving doxycycline or azithromycin in addition to ß-lactam therapy for the treatment of CAP were included for analysis. The primary outcomes were in-hospital and 30 day mortality. Secondary outcomes were ICU and hospital length-of-stay, 30 day readmission, days of mechanical ventilation, escalation and duration of antibiotics, adverse effects such as Clostridioides difficile infection and QTc prolongation. RESULTS: Sixty-three patients were in the azithromycin group and eighty-six patients in the doxycycline group. Both groups had similar APACHE IV and CURB-65 scores. The mean Charlson Comorbidity Index score was higher for the doxycycline group compared with the azithromycin group (P = 0.04). There was no statistically significant difference in in-hospital and 30 day mortality between the groups (P = 0.53, P = 0.57). There were no significant differences in any of the secondary outcomes. CONCLUSIONS: MICU patients with severe CAP who received doxycycline versus azithromycin in addition to ß-lactam treatment showed no significant differences in outcomes. These data offer support for inclusion of doxycycline as an alternative regimen in current IDSA recommendations.

Melatonin aspiration: Treatment with flexible bronchoscopy.

A 68-year-old male with past medical history 84 pack year smoking history (quit in 2000), mild chronic obstructive pulmonary disease (COPD), adenocarcinoma of right upper lobe treated with surgery and chemoradiation, and melanoma resection in 2013 presented with a one-month history of cough with sputum production and progressive dyspnea on exertion. He did not improve with standard treatment of antibiotics and steroids. He underwent flexible bronchoscopy that revealed an aspirated pill. This was successfully removed in the same session with the flexible bronchoscope.

Isolated pulmonary amyloidoma: A rare cause of solitary pulmonary nodule.

Pulmonary nodules are a frequent finding on imaging, especially given screening guidelines for lung cancer with low dose computed tomography (CT) scan. Here, we report a case with a single pulmonary nodule in a patient exposed to coal dust and asbestos. The nodule had benign features, but it showed an increase in size on repeated imaging. A CT-guided biopsy followed by mass spectrometry of the sample identified the nodule as the AL subtype of amyloidoma. A bone marrow biopsy was without evidence for malignancy including lymphoma. Nodular pulmonary amyloidosis (NPA) is rare, and a biopsy is required to establish the diagnosis. NPA generally does not affect lung function or impact survival; thus NPA does not require specific therapy. This case is the first documented case associated with coal-dust exposure. High-risk patients need to be followed longitudinally due to association of amyloidosis with lymphoma and other systemic conditions.

Outcomes of Patients With Sepsis and Septic Shock Requiring Source Control: A Prospective Observational Single-Center Study.

Source control is important in management of septic shock. We studied differences in outcomes of patients with sepsis and septic shock who required source control intervention compared with those who did not need such intervention and the effect of the timing of source control on various clinical outcomes. DESIGN: Prospective observational study from February 28, 2020, to March 31, 2021. SETTING: Medical ICU of academic quaternary medical center. PATIENTS: Two hundred five adult (≥18 yr) ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were divided into a medical treatment group and a source control group. Patients requiring source control were further divided into early (intervention performed < 24 hr) and late (≥ 24 hr) source control groups. The primary outcomes were 30-day and ICU mortality. Secondary outcomes were ICU and hospital length of stay (LOS), days on mechanical ventilation, and need for renal replacement therapy. A total of 45.9% patients underwent source control. Of these, early source control was performed in 44.7% and late source control in 55.3% of patients. There was no significant difference in 30-day mortality or ICU mortality in the medical versus source control groups or in early versus late source control groups. Compared with the medical group, mean hospital LOS (11.5 vs 17.4 d; p < 0.01) and ICU LOS (5.2 vs 7.7 d; p < 0.01) were longer in the source control group. The hospital LOS (12.5 vs 21.4 d; p < 0.01) and ICU LOS (5.2 vs 9.7 d; p < 0.01) were also longer in patients who had delayed source control than in patients who had early source control. There were no significant differences in other outcomes. CONCLUSIONS: Although mortality was similar, patients who had delayed source control had a longer ICU and hospital LOS. Early source control may improve health care utilization in septic shock patients.

Redox imbalance in COVID-19 pathophysiology.

BACKGROUND: The pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required. METHODS: COVID-19 subjects (n = 64) and control subjects (n = 19) were enrolled, and blood was drawn within 72 h of diagnosis. Serum multiplex assays and peripheral blood mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome. RESULTS: Significantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects. CONCLUSION: Herein we demonstrate a significant redox imbalance during COVID-19 infection affirming the potential for manipulation of oxidative stress pathways as a new therapeutic strategy COVID-19. However, further work is requisite for detailed identification of oxidants (O2•-, H2O2 and/or circulating transition metals such as Fe or Cu) contributing to this imbalance to avoid the repetition of failures using non-specific antioxidant supplementation.

Coagulation Studies Are Not Predictive of Hematological Complications of COVID-19 Infection.

Objectives Thrombotic and bleeding complications are common in COVID-19 disease. In a prospective study, we performed a comprehensive panel of tests to predict the risk of bleeding and thrombosis in patients admitted with hypoxic respiratory failure due to severe COVID-19 infection. Methods We performed a single center (step down and intensive care unit [ICU] at a quaternary care academic hospital) prospective study. Sequentially enrolled adult (≥18 years) patients were admitted with acute hypoxic respiratory failure due to COVID-19 between June 2020 and November 2020. Several laboratory markers of coagulopathy were tested after informed and written consent. Results Thirty-three patients were enrolled. In addition to platelet counts, prothrombin time, and activated partial thromboplastin time, a series of protocol laboratories were collected within 24 hours of admission. These included Protein C, Protein S, Antithrombin III, ADAMTS13, fibrinogen, ferritin, haptoglobin, and peripheral Giemsa smear. Patients were then monitored for the development of hematological (thrombotic and bleeding) events and followed for 30 days after discharge. Twenty-four patients (73%) required ICU admissions. At least one laboratory abnormality was detected in 100% of study patients. Nine patients (27%) suffered from significant hematological events, and four patients had a clinically significant bleeding event requiring transfusion. No significant association was observed between abnormalities of coagulation parameters and the incidence of hematologic events. However, a higher SOFA score (10.89 ± 3.48 vs. 6.92 ± 4.10, p = 0.016) and CKD (5/9 [22.2%] vs. 2/24 [12.5%] p = 0.009) at baseline were associated with the development of hematologic events. 33.3% of patients died at 30 days. Mortality was similar in those with and without hematological events. Reduced ADAMTS13 level was significantly associated with mortality. Conclusion Routine extensive testing of coagulation parameters did not predict the risk of bleeding and thrombosis in COVID-19 patients. Thrombotic and bleeding events in COVID-19 patients are not associated with a higher risk of mortality. Interestingly, renal dysfunction and a high SOFA score were found to be associated with increased risk of hematological events.

The Implementation of Protocol-Based Utilization of Neuromuscular Blocking Agent Using Clinical Variables in Acute Respiratory Distress Syndrome Patients.

OBJECTIVES: The recent conflicting data on the mortality benefit of neuromuscular blocking agents in acute respiratory distress syndrome and the potential adverse effects of continuous neuromuscular blocking agent necessitates that these medications should be used judiciously with dose reduction in mind. The aims of the study were to improve the process of care by provider education of neuromuscular blocking agent titration and monitoring and to determine the impact of clinical endpoint based neuromuscular blocking agent titration protocol. DESIGN: We conducted a proof-of-concept historically controlled study of protocol-based intervention standardizing paralytic monitoring and titration using clinical variables. Education of the protocol was provided to ICU staff via bedside teaching and workshops. The primary outcomes were the time to reach goal paralysis and cumulative neuromuscular blocking agent dose. Secondary outcomes included maintenance of deeper sedation (Richmond Agitation and Sedation Scale -5) prior to neuromuscular blocking agent initiation, total time on mechanical ventilation, length of stay, and mortality. SETTING: Medical ICU at a quaternary academic hospital between March 2019 and June 2020. PATIENTS: Adult severe acute respiratory distress syndrome (Pao2/Fio2 <150) patients requiring neuromuscular blocking agent for greater than or equal to 12 hours. Eighty-two patients fulfilled inclusion criteria, 46 in the control group and 36 in the intervention group. INTERVENTIONS: Education and implementation of standardized protocol. MEASUREMENTS AND MAIN RESULTS: Compared with the control group, the time to reach goal paralysis in the intervention group was shorter (8.55 ± 9.4 vs 2.63 ± 5.9 hr; p < 0.0001) on significantly lower dose of cisatracurium (total dose 1,897.96 ± 1,241.0 vs 562.72 ± 546.7 mg; p < 0.0001 and the rate 5.84 ± 2.66 vs 1.99 ± 0.95 µg/kg/min; p < 0.0001). Deeper sedation was achieved at the time of initiation of neuromuscular blocking agent in the intervention arm (mean Richmond Agitation and Sedation Scale -3.3 ± 1.9 vs -4.3 ± 1.7; p = 0.015). There was no significant difference in total time on mechanical ventilation, length of ICU stay, length of hospital stay, and mortality between the two groups. CONCLUSIONS: Implementation of comprehensive education, standardization of sedation prior to neuromuscular blocking agent initiation, integration of clinical variables in determining paralysis achievement, and proper use of peripheral nerve stimulation served as optimal strategies for the titration and monitoring of neuromuscular blocking agent in acute respiratory distress syndrome. This reduced drug utilization while continuing to achieve benefit without causing adverse effects.

Utility of FDG PET/CT for assessment of lung nodules identified during low dose computed tomography screening.

BACKGROUND: Many clinical guidelines recommend FDG PET/CT for the evaluation of pulmonary nodules ≥8 mm detected during low dose computed tomography (LDCT) lung cancer screening. However, its added value in this setting requires confirmation. We evaluated the clinical utility of FDG PET/CT, including incidental findings, during the evaluation of lung nodules detected on LDCT screening. METHODS: A retrospective cohort study was performed among 75 patients who completed FDG PET/CT between January 2010 and December 2017, after lung nodules > 8 mm had been detected on LDCT lung cancer screening. We report demographic variables, characteristics of the initial nodules on LDCT and FDG PET/CT, incidental findings on FDG PET/CT, as well as further work up performed and the influence of FDG PET/CT findings on management. RESULTS: Nodules were reported to be benign on FDG PET/CT in 38/75 (50.6%) patients. Physicians chose either radiological follow-up or no further work up in all 38. FDG PET/CT was indeterminate or suggested malignancy in 37 (49.3%) patients. Biopsy was performed in 32 (86%) of these patients. Incidental findings on FDG PET/CT were reported in 37/75 (49%) patients. Further work-up of incidental findings was performed in 21/75 (28%) of patients. CONCLUSIONS: In this study, for majority of individuals with lung nodules identified during LDCT lung cancer screening, FDG PET/CT results were able to guide physicians in choosing between routine follow up or invasive biopsies. Conversely, 28% of these patients required additional investigations to address incidental findings.

An unusual endobronchial lesion: expanding the differential diagnosis.

Synovial sarcoma is a rare tumour, accounting for approximately 2.5-10% of all soft tissue sarcomas. In the thorax, it most often presents as a large, homogenous mass and, most commonly, is the result of extrathoracic tumour metastasis. Here, we report a case of a 73-year-old male who presented to the hospital after a motor vehicle collision. Chest computed tomography demonstrated a 2.0 × 2.4 cm left lower lobe pulmonary nodule with endobronchial extension and a 2.5 × 2.1 cm right-sided kidney mass. He was eventually diagnosed with monophasic synovial sarcoma. To date, only seven other cases of primary pulmonary synovial sarcoma with endobronchial extension have been reported. A review of the cases and literature is discussed.

Derivation and Validation of a Prognostic Model to Predict 6-Month Mortality in an Intensive Care Unit Population.

RATIONALE: Identification of terminally ill patients in the intensive care unit (ICU) would facilitate decision making and timely palliative care. OBJECTIVES: To develop and validate a patient-specific integrated prognostic model to predict 6-month mortality in medical ICU patients. METHODS: A longitudinal prospective cohort study of temporally split samples of 1,049 consecutive medical ICU patients in a tertiary care hospital was performed. For each patient, we collected demographic data, Acute Physiology and Chronic Health Evaluation III score, Charlson comorbidity index, intensivist response to a surprise question (SQ; "Would I be surprised if this patient died in the next 6 months?") on admission, and vital status at 6 months. RESULTS: Between November 2013 and May 2015, derivation and validation cohorts of 500 and 549 consecutive patients were studied to develop a multivariate logistic regression model. In the multivariate logistic regression model, Charlson comorbidity index (P = 0.033), Acute Physiology and Chronic Health Evaluation III score (P < 0.001), and SQ response (P < 0.001) were predictors of vital status at 6 months. The odds of dying within 6 months were significantly higher when the SQ was answered "no" than when it was answered "yes" (odds ratio, 7.29; P < 0.001). The c-statistic for the derivation and validation cohorts were 0.832 (95% confidence interval, 0.795-0.870) and 0.84 (95% confidence interval, 0.806-0.875), respectively. CONCLUSIONS: Our integrated prognostic model, which includes the SQ, has strong discrimination and calibration to predict 6-month mortality in medical ICU patients. This model can aid clinicians in identifying ICU patients who may benefit from the integration of palliative care into their treatment.

Intralobar bronchopulmonary sequestra in adults over age 50: case series and review.

INTRODUCTION: Bronchopulmonary sequestration (BPS) is a rare congenital lung malformation, comprising only 0.15 to 6.4% of all cases of congenital lung malformation. It is characterized by an abnormal segment of bronchopulmonary tissue supplied by an aberrant systemic artery. Diagnostic delays are common in the adult patients since the symptoms often mimic other common diseases such as pneumonia, emphysema, and lung abscess. In 60% of cases, intralobar pulmonary sequestration (ILS) is typically diagnosed at age 20 or younger and is rarely found in adults older than 40 years. Since a heightened clinical suspicion needs to be maintained to entertain this diagnosis in the adult population, we conducted a retrospective chart review of all adult patients at our institution over age 50. MATERIALS AND METHODS: A retrospective chart review of all adult patients evaluated at our institution with a pathological proven diagnosis of BPS and subsequent surgical correction from January 1993 through December 2008 was conducted. Data obtained included demographics, clinical presentation, diagnostic procedures, location and origin of the lesion, operative therapy, histology of the surgical specimen, and postoperative complications. RESULTS: Three patients had undergone surgical correction for BPS. All three patients at our institution were female. The average age was 59 years with a range from 57 to 62 years. All three patients had symptoms preoperatively including intermittent cough and recurrent pneumonia. Radiologic evaluation revealed an enlarging lung mass in one patient and lesions suggestive of BPS in two of the patients. Two patients had a right lower lobe sequestration and one patient had a left lower lobe sequestration. All three patients underwent lower lobectomies without any significant postoperative complications. CONCLUSION: BPS in patients older than 50 is very rare. Persistent lower lobe consolidation in medial or posterior basal segments accompanied by an aberrant artery in adults should heighten suspicion for it. Recurrent pneumonias, cough, chest pain occur in the majority of patients. Surgical excision after correctly identifying the aberrant vessel is curative and also diagnostic in some cases.

Strongyloides hyperinfection syndrome complications: a case report and review of the literature.

Strongyloidiasis is a major global health challenge that is often underestimated in many countries. In immuno-compromised hosts, an autoinfection can go unchecked with large numbers of invasive Strongyloides larvae disseminating widely and causing hyperinfection, with fatal consequences. This review will highlight a case of gram negative bacteremia complicated by meningitis and Adult Respiratory Distress Syndrome (ARDS) as a fatal outcome of Strongyloides hyperinfection, commonly known to occur in the setting of immunosuppression. A middle aged female with chronic lymphocytic leukemia and hypogammaglobulinemia presented with severe respiratory distress requiring intubation. She had been on intermittent corticosteroids and multiple courses of antibiotics for the past six months for COPD exacerbations. Bronchoalveolar lavage showed Strongyloides stercoralis. Blood cultures grew Vancomycin Resistant Enterococci and a few days later Vancomycin Sensitive Enterococcus was found in the CSF. Afterwards, she grew Vancomycin Sensitive Enterococcus in the blood. She was treated with Ivermectin and Albendazole for Strongyloides and Linezolid and Vancomycin for these two different strains of E. faecium. After initial resolution of bacteremia and meningitis, she relapsed three weeks later with the same organism growing in the CSF. The clinical course continued to deteriorate with the development of significant neurological dysfunction. Poor nutritional state and ventilator associated pneumonia contributed to this downward trend. After a detailed discussion with the family, life support was discontinued and the patient succumbed to her illness.