Safety of Bronchoalveolar Lavage in Hematological Patients with Thrombocytopenia. A Retrospective Cohort Study.

Background: Hospitalized hematological patients often require bronchoalveolar lavage (BAL). Scarce evidence exists regarding the potential risks in patients with very severe thrombocytopenia (VST). Methods: This retrospective-cohort study included adult hematological in-patients with VST, defined as platelets<20x103/µL, undergoing BAL during 2012-2021. Mechanically ventilated patients or those with known active bleeding were excluded. Primary outcomes included major bleeding halting the BAL or deemed significant by the treating physician, need for any respiratory support other than low flow O2, or death within 24 hours. Any other bleedings were recorded as secondary outcomes. Results: Of the 507 patients included in the final analysis, the 281 patients with VST had lower hemoglobin (Md=0.3, p=0.003), longer prothrombin-time (Md=0.7s, p=0.025), higher chances of preprocedural platelet transfusion (RR 3.68, 95%CI [2.86,4.73]), and only one primary-outcome event (death of septic shock 21h postprocedurally) - compared with 3 (1.3%) events (two bleedings halting procedure and one need for non-invasive-ventilation) in patients with platelets ≥20x103/µL (p=0.219). The risk of minor spontaneously resolved bleeding was higher (RR=3.217, 95% CI [0.919,11.262]) in patients with VST (4.3% vs 1.3%, p=0.051). No association was found between the complications recorded and preprocedural platelets, age, aPTT, P.T., hematological status, or platelet transfusion. Conclusions: This data suggests BAL to be safe even when platelet counts are <20x103/µL.

Combining reservoir mask oxygenation with high-flow nasal cannula in the treatment of hypoxemic respiratory failure among patients with COVID-19 pneumonia: a retrospective cohort study.

BACKGROUND: Concerns regarding positive-pressure-ventilation for the treatment of coronavirus disease 2019 (COVID-19) hypoxemia led the search for alternative oxygenation techniques. This study aimed to assess one such method, dual oxygenation, i.e., the addition of a reservoir mask (RM) on top of a high-flow nasal cannula (HFNC). METHODS: In this retrospective cohort study, the records of all patients hospitalized with COVID-19 during 2020-2022 were reviewed. Patients over the age of 18 years with hypoxemia necessitating HFNC were included. Exclusion criteria were positive-pressure-ventilation for any indication other than hypoxemic respiratory failure, transfer to another facility while still on HFNC and "do-not-intubate/resuscitate" orders. The primary outcome was mortality within 30 days from the first application of HFNC. Secondary outcomes were intubation and admission to the intensive care unit. RESULTS: Of 659 patients included in the final analysis, 316 were treated with dual oxygenation and 343 with HFNC alone. Propensity for treatment was estimated based on background diagnoses, laboratories and vital signs upon admission, gender and glucocorticoid dose. Inverse probability of treatment weighted regression including age, body mass index, Sequential Organ Failure Assessment (SOFA) score and respiratory rate oxygenation index showed treatment with dual oxygenation to be associated with lower 30-day mortality (adjusted hazard ratio, 0.615; 95% confidence interval, 0.469-0.809). Differences in the secondary outcomes did not reach statistical significance. CONCLUSIONS: Our study suggests that the addition of RM on top of HFNC may be associated with decreased mortality in patients with severe COVID-19 hypoxemia.

An unexpected diagnosis of a 57-year-old women with migratory pulmonary infiltrates.

A 57-year-old female presented with sudden shortness of breath and migratory pulmonary infiltrates on imaging, which corresponds with a diagnosis of cryptogenic organizing pneumonia. Initial treatment with corticosteroids showed only mild improvement during follow-up. BAL was performed and revealed diffuse alveolar hemorrhage. Immune testing showed positive P-ANCA with positive MPO, leading to a diagnosis of microscopic polyangiitis.

Functional Capacity in Patients Who Recovered from Mild COVID-19 with Exertional Dyspnea.

BACKGROUND: Post mild COVID-19 dyspnea is poorly understood. We assessed physiologic limitations in these patients. METHODS: Patients with post mild COVID-19 dyspnea (group A) were compared (pulmonary function tests, 6-min walk test (6MWT), echocardiography and cardiopulmonary exercise test (CPET)) to post moderate/severe COVID-19 (group B) and to CPET and spirometry of patients with unexplained dyspnea (group C). RESULTS: The study included 36 patients (13 in A, 9 in B and 14 in C). Diffusion capacity was lower in group B compared to group A (64 ± 8 vs. 85 ± 9% predicted, p = 0.014). 6MWT was normal and similar in both patient groups. Oxygen uptake was higher in group A compared to groups B and C (108 ± 14 vs. 92 ± 13 and 91 ± 23% predicted, p = 0.013, 0.03, respectively). O2 pulse was normal in all three groups but significantly higher in the mild group compared to the control group. Breathing reserve was low/borderline in 2/13 patients in the mild group, 2/9 in the moderate/severe group and 3/14 in the control group (NS). CONCLUSIONS: Patients with post mild COVID-19 dyspnea had normal CPET, similar to patients with unexplained dyspnea. Other mechanisms should be investigated and the added value of CPET to patients with post mild COVID-19 dyspnea is questionable.

The diagnostic value of nasal microbiota and clinical parameters in a multi-parametric prediction model to differentiate bacterial versus viral infections in lower respiratory tract infections.

BACKGROUND: The ability to accurately distinguish bacterial from viral infection would help clinicians better target antimicrobial therapy during suspected lower respiratory tract infections (LRTI). Although technological developments make it feasible to rapidly generate patient-specific microbiota profiles, evidence is required to show the clinical value of using microbiota data for infection diagnosis. In this study, we investigated whether adding nasal cavity microbiota profiles to readily available clinical information could improve machine learning classifiers to distinguish bacterial from viral infection in patients with LRTI. RESULTS: Various multi-parametric Random Forests classifiers were evaluated on the clinical and microbiota data of 293 LRTI patients for their prediction accuracies to differentiate bacterial from viral infection. The most predictive variable was C-reactive protein (CRP). We observed a marginal prediction improvement when 7 most prevalent nasal microbiota genera were added to the CRP model. In contrast, adding three clinical variables, absolute neutrophil count, consolidation on X-ray, and age group to the CRP model significantly improved the prediction. The best model correctly predicted 85% of the 'bacterial' patients and 82% of the 'viral' patients using 13 clinical and 3 nasal cavity microbiota genera (Staphylococcus, Moraxella, and Streptococcus). CONCLUSIONS: We developed high-accuracy multi-parametric machine learning classifiers to differentiate bacterial from viral infections in LRTI patients of various ages. We demonstrated the predictive value of four easy-to-collect clinical variables which facilitate personalized and accurate clinical decision-making. We observed that nasal cavity microbiota correlate with the clinical variables and thus may not add significant value to diagnostic algorithms that aim to differentiate bacterial from viral infections.

Dyspnea With Unilateral Pulmonary Ground Glass Opacities and Cavitary Lesions.

CASE PRESENTATION: A 62-year-old man presented with a 3-month history of shortness of breath and a dry cough. He had a medical history of hypertension (without use of angiotensin-converting enzyme inhibitors), hyperlipidemia, depression, and 10-pack-years of cigarette smoking several decades ago. He was a limousine driver and denied any history of occupational high-risk exposures. The patient denied significant weight gain or weight loss, night sweats, fevers, hemoptysis, chest pain, or palpitations. He had a normal physical examination. Pulmonary function studies with a hemoglobin level of 12.9 gm/dL revealed normal spirometry, normal lung volumes, and moderately low diffusion capacity (56% of predicted). A 6-minute walk test showed mild desaturation (97% to 92% after 432 m). Stress echo revealed ejection fraction of 60% with no regional wall motion abnormalities, no evidence of impaired diastolic filling, estimated peak pulmonary artery pressure 35 to 40 mm Hg, and no valvular abnormalities with desaturation to 87% during the test. Extensive rheumatologic, infectious disease, and hypercoagulability workup were unremarkable. BAL was negative for malignancy, infection, or eosinophilic lung disease.

Shortness of Breath in a 38-Year-Old Woman With Pulmonary and Hepatic Nodules.

CASE PRESENTATION: A 38-year-old African American woman with a history of menometrorrhagia on previous estrogen therapy and a previously biopsied benign thyroid nodule with recent interval enlargement presented with symptoms of shortness of breath on exertion, an intermittent nonproductive cough, and right upper quadrant abdominal pain for 1 year. She denied wheezing, hemoptysis, fevers, night sweats, or unintentional weight loss. Socially, the patient was a lifelong nonsmoker and denied alcohol or drug use. Travel history was not significant, and she had no contributory occupational, environmental, or animal exposures. Recent cancer screening that included Papanicolaou smear and mammography were negative for neoplasia. Vital signs were normal, and ambulatory pulse oximetry did not demonstrate evidence of oxygen desaturation. Physical examination demonstrated normal respiratory effort, diffuse vesicular breath sounds, and a soft abdomen without hepatomegaly or right upper quadrant tenderness.

Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by constant threat of acute exacerbation of IPF (AE-IPF). It would be significant to identify risk factors of AE-IPF. We sought to determine the prognostic value of lung transplantation candidacy testing for AE-IPF and describe explant pathology of recipients with and without AE-IPF before lung transplantation. METHODS: Retrospective cohort study of 89 IPF patients listed for lung transplantation. Data included pulmonary function testing, echocardiography, right heart catheterisation, imaging, oesophageal pH/manometry and blood tests. Explanted tissue was evaluated by pulmonary pathologists and correlated to computed tomography (CT) findings. RESULTS: Out of 89 patients with IPF, 52 were transplanted during stable IPF and 37 had AE-IPF before transplantation (n=28) or death (n=9). There were no substantial differences in candidacy testing with and without AE-IPF. AE-IPF had higher rate of decline of forced vital capacity (FVC) (21±22% versus 4.8±14%, p=0.00019). FVC decline of >15% had a hazard ratio of 7.2 for developing AE-IPF compared to FVC decline of <5% (p=0.004). AE-IPF had more secondary diverse histopathology (82% versus 29%, p<0.0001) beyond diffuse alveolar damage. There was no correlation between ground-glass opacities (GGO) on chest CT at any point to development of AE-IPF (p=0.077), but GGO during AE-IPF predicted secondary pathological process beyond diffuse alveolar damage. CONCLUSIONS: Lung transplantation candidacy testing including reflux studies did not predict AE-IPF besides FVC absolute decline. CT did not predict clinical or pathological AE-IPF. Secondary diverse lung pathology beyond diffuse alveolar damage was present in most AE-IPF, but not in stable IPF.

Acute exacerbations of COPD versus IPF in patients with combined pulmonary fibrosis and emphysema.

RATIONALE: Patients with combined pulmonary fibrosis and emphysema (CPFE) may develop acute exacerbations of IPF (AE-IPF) or COPD (AE-COPD). The incidence and the characteristics of exacerbations in patients with CPFE (e.g., COPD vs IPF) have not been well described. OBJECTIVES: To compare the incidence and rate of exacerbations in patients with CPFE vs. IPF and evaluate their effect on clinical outcomes. METHODS: Comprehensive clinical data from CPFE and IPF patients were retrospectively reviewed. Baseline characteristics including lung function data, oxygen requirements, and pulmonary hemodynamics, were collected. Acute exacerbation events in both groups were defined clinically and radiographically. In the CPFE group, two patterns of exacerbations were identified. AE-COPD was defined clinically by symptoms of severe airflow obstruction causing respiratory failure and requiring hospitalization. Radiographic data were also defined based on previously published literature. AE-IPF was defined clinically as an acute hypoxic respiratory failure, requiring hospitalization and treatment with high dose corticosteroids. Radiographically, patients had to have a change in baseline imaging including presence of ground-glass opacities, interlobular septal thickening or new consolidations; that is not fully explained by other etiologies. RESULTS: Eighty-five CPFE patients were retrospectively compared to 112 IPF patients. Of 112 patients with IPF; 45 had AE-IPF preceding lung transplant (40.18%) compared to 12 patients in the CPFE group (14.1%) (p < 0.05). 10 patients in the CPFE group experienced AE-COPD (11.7%). Patients with AE-IPF had higher mortality and more likely required mechanical ventilation and extracorporeal membrane oxygenation (ECMO) compared to patients with AE-COPD, whether their underlying disease was IPF or CPFE. CONCLUSIONS: CPFE patients may experience either AE-IPF or AE-COPD. Patients with CPFE and AE-COPD had better outcomes, requiring less intensive therapy compared to patients with AE-IPF regardless if underlying CPFE or IPF was present. These data suggest that the type of acute exacerbation, AE-COPD vs AE-IPF, has important implications for the treatment and prognosis of patients with CPFE.

Pulmonary vasculopathy in explanted lungs from patients with interstitial lung disease undergoing lung transplantation.

BACKGROUND: Pulmonary hypertension (PH) causes increased morbidity and mortality in patients with interstitial lung diseases (ILD). Classification schemes, while well-characterised for the vasculopathy of idiopathic PH, have been applied, unchallenged, to ILD-related PH. We evaluated pulmonary arterial histopathology in explanted human lung tissue from patients who were transplanted for advanced fibrotic ILD. METHODS: Lung explants from 38 adult patients who underwent lung transplantation were included. Patients were divided into three groups: none, mild/moderate and severe PH by mean pulmonary artery pressure (mPAP) measured at pre lung transplantation right heart catheterisation (RHC). Grading of pulmonary vasculopathy according to Heath and Edwards scheme, and prelung transplantation evaluation data were compared between the groups. RESULTS: 38 patients with fibrotic ILDs were included, the majority (21) with idiopathic pulmonary fibrosis. Of the 38 patients, 18 had severe PH, 13 had mild/moderate PH and 7 had no PH by RHC. 16 of 38 patients had severe pulmonary arterial vasculopathy including vascular occlusion with intimal fibrosis and/or plexiform lesions. There were no correlations between mPAP and lung diffusion with the severity of pulmonary arterial pathological grade (Spearman's rho=0.14, p=0.34, rho=0.11, p=0.49, respectively). CONCLUSIONS: Patients with end stage ILD had severe pulmonary arterial vasculopathy in their explanted lungs irrespective of the presence and/or severity of PH as measured by RHC. These findings suggest that advanced pulmonary arterial vasculopathy is common in patients with advanced fibrotic ILD and may develop prior to the clinical detection of PH by RHC.

Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment).

Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.

Effect of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplantation Outcome.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has an expected median survival of 3 months. Lung transplantation is a potentially lifesaving therapy for AE-IPF. However, the current knowledge of transplantation outcomes during AE-IPF is limited to a few small retrospective studies, reporting only 1-year post-transplantation survival. METHODS: Study population included patients with IPF consecutively listed for lung transplantation at a single institution between the years 2012 and 2016. We collected lung allocation score (LAS), hospitalization, and survival data. The primary outcome was survival among patients transplanted during stable IPF vs during AE-IPF. RESULTS: Of 89 patients with IPF listed for lung transplantation, 52 were transplanted during stable IPF and 37 were hospitalized due to AE-IPF. Of these 37 patients, nine died before transplantation, and 28 were transplanted during AE-IPF. Fifty percent of patients transplanted during AE-IPF died in a mean follow-up of 1.6 ± 1.2 years compared with 12% of patients transplanted during stable IPF who died in a mean follow-up of 2.6 ± 1.2 years. The Kaplan-Meier survival curves post-transplantation after 1 and 3 years for patients who were transplanted during stable IPF were 94% and 90% vs 71% and 60% in patients who were transplanted during AE-IPF (P = .0001). LAS above 80 conferred a 3-year hazard ratio for mortality of 5.7 vs LAS lower than 80 (95% CI, 2.33-14.0; P < .0005). CONCLUSIONS: Patients with IPF transplanted during AE-IPF had significantly worse short-term and long-term survival compared with patients transplanted during stable IPF. Patients with AE-IPF and very high LAS may not experience the survival advantage expected from lung transplantation.

Alteration in upper airway dilator muscle coactivation during sleep: comparison of patients with obstructive sleep apnea and healthy subjects.

In patients with obstructive sleep apnea (OSA), substantial increases in genioglossus (GG) activity during hypopneas/apneas usually fail to restore normal airflow. We have previously suggested that sleep-induced alteration in tongue muscle coordination may explain this finding, as retractor muscle coactivation was reduced during sleep compared with wakefulness. The present study was undertaken to evaluate whether these alterations in dilator muscle activation during sleep play a role in the pathogenesis of OSA and whether coactivation of additional peripharyngeal muscles (non-GG muscles: styloglossus, geniohyoid, sternohyoid, and sternocleidomastoid) is also impaired during sleep. We compared GG and non-GG muscle electromyographic (EMG) activity in 8 patients with OSA and 12 healthy subjects during wakefulness while breathing through inspiratory resistors with the activity observed during sleep toward the end of flow limitation, before arousal, at equivalent esophageal pressures. During wakefulness, resistive breathing triggered increases in both GG and non-GG muscle activity. During sleep, flow limitation was associated with increases in GG-EMG that reached, on average, >2-fold the level observed while awake. In contrast, EMGs of the non-GG muscles, recorded simultaneously, reached, on average, only ~2/3 the wakefulness level. We conclude that during sleep GG activity may increase to levels that substantially exceed those sufficient to prevent pharyngeal collapse during wakefulness, whereas other peripharyngeal muscles do not coactivate during sleep in both patients with OSA and healthy subjects. We speculate that upper airway muscle dyssynchrony during sleep may explain why GG-EMG activation fails to alleviate flow limitation and stabilize airway patency during sleep. NEW & NOTEWORTHY Pharyngeal obstruction during sleep may trigger genioglossus activity to levels substantially exceeding those observed during wakefulness, without ameliorating flow limitation. In contrast, other peripharyngeal muscles exhibit a much lower activity during sleep in both patients with obstructive sleep apnea and healthy subjects. Coordinated muscular synergy stabilizes the pharynx despite relatively low activity while awake, yet even higher genioglossal activity allows the pharynx to obstruct when simultaneous activity of other dilator muscles is inadequate during sleep.

A novel host-protein assay outperforms routine parameters for distinguishing between bacterial and viral lower respiratory tract infections.

Bacterial and viral lower respiratory tract infections (LRTIs) are often clinically indistinguishable, leading to antibiotic overuse. We compared the diagnostic accuracy of a new assay that combines 3 host-biomarkers (TRAIL, IP-10, CRP) with parameters in routine use to distinguish bacterial from viral LRTIs. Study cohort included 184 potentially eligible pediatric and adult patients. Reference standard diagnosis was based on adjudication by an expert panel following comprehensive clinical and laboratory investigation (including respiratory PCRs). Experts were blinded to assay results and assay performers were blinded to reference standard outcomes. Evaluated cohort included 88 bacterial and 36 viral patients (23 did not fulfill inclusion criteria; 37 had indeterminate reference standard outcome). Assay distinguished bacterial from viral LRTI patients with sensitivity of 0.93±0.06 and specificity of 0.91±0.09, outperforming routine parameters, including WBC, CRP and chest x-ray signs. These findings support the assay's potential to help clinicians avoid missing bacterial LRTIs or overusing antibiotics.

[A PROSPECTIVE STUDY TO INCREASE THE AWARENESS OF VENOUS THROMBOEMBOLISM PROPHYLAXIS IN INTERNAL MEDICINE WARDS].

INTRODUCTION: Venous thromboembolism (VTE) events are a significant risk factor for morbidity and mortality among hospitalized patients and 50-75% of the events occur in internal medicine wards. Despite the proven efficiency of prophylactic treatments, their usage in hospitals is underutilized. Multiple studies have shown that only 30-50% of the high risk VTE patients are treated prophylactically. Interventional programs were shown to significantly increase the awareness and hence, the percent of patients treated. However, there are no official guidelines for prophylaxis implementation among hospital personnel in Israel. METHODS: We conducted a prospective study of patients hospitalized in internal medicine wards to estimate the risk of VTE events and the prophylaxis rate. Patients were randomly selected and evaluated for VTE risk and treatment provided. During daily staff meetings on random sampling days, an open inquiry was conducted for each patient's management regarding VTE prophylaxis. This supervision was carried out for 3 consecutive months and 6 months later, to evaluate the implementation of the process. RESULTS: A total of 205 patients were sampled during the study. During the first month, 35% of the patients with indications for prophylaxis were treated. This percent increased to 50% in the second month, 60% in the third, and to 86% after six months (p<0.0001). CONCLUSIONS: The awareness of VTE prophylaxis was low, and only a third of the patients with indications for prophylaxis were treated. The awareness implementation was slow and incremental, and increased from 35% to 86%. We conclude that the supervision and training on VTE prophylaxis is efficient and essential.

Widespread osteoblastic metastases and marked elevation of CA19-9 as a presentation of signet ring cell gastric carcinoma.

Widespread osteoblastic metastases, as well as marked elevations of CA19-9 and carcino-embryonic antigen (CEA), are the initial manifestations of gastric signet ring cell carcinoma. CT Imaging revealed diffuse sclerotic metastases in the axial skeleton. It was only following gastric biopsy that the primary site of metastatic bone tumor was identified. Recent studies suggest that early diagnosis of cancer origin, including tumor molecular profiling, may dictate specific therapy, improve prognosis and increase patient survival rates.

Delayed Bleeding after Percutaneous Liver Biopsy.

Percutaneous liver biopsy (PLB) is a common procedure in patients with liver disease. Bleeding after PLB is rare, with an incidence of 0.35%. Most bleeding complications present within 24 h after biopsy. A 56-year-old woman was admitted to our hospital due to severe and sudden right upper quadrant (RUQ) abdominal pain 10 days after ultrasound (US)-guided PLB. CT study revealed both intrahepatic and intraperitoneal bleeding, and Hb levels decreased by 3.2 g/dl within a few hours. Such a prolonged delay in PLB-related bleeding has not been previously described in the medical literature. LEARNING POINTS: Bleeding after liver biopsy is very rare, with an incidence of 0.35%.Approximately 95% of bleeding complications occur within 24 h.Physicians should be aware of rare delayed presentation in the days following liver biopsy.