Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers.

BACKGROUND & AIMS: Homozygosity for the Pi∗Z variant of the gene that encodes the alpha-1 antitrypsin peptide (AAT), called the Pi∗ZZ genotype, causes a liver and lung disease called alpha-1 antitrypsin deficiency. Heterozygosity (the Pi∗MZ genotype) is a risk factor for cirrhosis in individuals with liver disease. Up to 4% of Europeans have the Pi∗MZ genotype; we compared features of adults with and without Pi∗MZ genotype among persons without preexisting liver disease. METHODS: We analyzed data from the European Alpha-1 Liver Cohort, from 419 adults with the Pi∗MZ genotype, 309 adults with the Pi∗ZZ genotype, and 284 individuals without the variant (noncarriers). All underwent a comprehensive evaluation; liver stiffness measurements (LSMs) were made by transient elastography. Liver biopsies were analyzed to define histologic and biochemical features associated with the Pi∗Z variant. Levels of serum transaminases were retrieved from 444,642 participants, available in the United Kingdom biobank. RESULTS: In the UK biobank database, levels of serum transaminases were increased in subjects with the Pi∗MZ genotype compared with noncarriers. In the Alpha-1 Liver Cohort, adults with Pi∗MZ had lower levels of gamma-glutamyl transferase in serum and lower LSMs than adults with the Pi∗ZZ variant, but these were higher than in noncarriers. Ten percent of subjects with the Pi∗MZ genotype vs 4% of noncarriers had LSMs of 7.1 kPa or more (adjusted odds ratio, 4.8; 95% confidence interval, 2.0-11.8). Obesity and diabetes were the most important factors associated with LSMs ≥7.1 kPa in subjects with the Pi∗MZ genotype. AAT inclusions were detected in liver biopsies of 63% of subjects with the Pi∗MZ genotype, vs 97% of subjects with the Pi∗ZZ genotype, and increased with liver fibrosis stages. Subjects with the Pi∗MZ genotype did not have increased hepatic levels of AAT, whereas levels of insoluble AAT varied among individuals. CONCLUSIONS: Adults with the Pi∗MZ genotype have lower levels of serum transaminases, fewer AAT inclusions in liver, and lower liver stiffness than adults with the Pi∗ZZ genotype, but higher than adults without the Pi∗Z variant. These findings should help determine risk of subjects with the Pi∗MZ genotype and aid in counseling.

Analysis of the accuracy of the Wells scale in assessing the probability of lower limb deep vein thrombosis in primary care patients practice.

BACKGROUND: The clinical picture of deep vein thrombosis (DVT) is nonspecific. Therefore assessment of the probability of occurrence of DVT plays a very important part in making a correct diagnosis of DVT. The aim of our prospective study was to assess the accuracy of the Wells scale in primary care setting in diagnostic procedure of suspected deep vein thrombosis. METHODS: In the period of 20 - months (from 2007 to 2009) a group of residents from one of the urban districts of Warsaw, who reported to family doctors (22 primary care physicians were involved in the study) with symptoms of DVT were assessed on the probability of occurrence of deep vein thrombosis using the Wells scale. Family doctors were aware of symptoms of DVT and inclusion patients to this study was based on clinical suspicion of DVT. Patients were divided into three groups, reflecting probability of DVT of the lower limbs. To confirm DVT a compression ultrasound (CUS) test was established. We analyzed the relationship between a qualitative variable and a variable defined on an original scale (incidence of DVT versus Wells scale count) using the Mann-Whitney test. Chi-square test compared rates of DVT events in all clinical probability groups. Patient were follow up during 3 months in primary care setting. RESULTS: In the period of 20 months (from 2007 to 2009) a total number of 1048 patients (male: 250 , female: 798 mean age: 61.4) with symptoms suggestive of DVT of the lower extremities entered the study. Among the 100 patients classified in the group with a high probability of DVT of the lower extremities, 40 (40%) patients (proximal DVT - 13; distal DVT - 27) were diagnosed with it (95% CI [30.94% -49.80%]). In the group with a moderate probability consisting of 302 patients, DVT of the lower extremities was diagnosed in 19 (6.29%) patients (95% CI [4.06% -9.62%]), (proximal DVT - 1; distal DVT - 18). Of the 646 patients with a low probability of DVT of the lower extremities distal DVT was diagnosed in 1 (0.15%) patient (95% CI [0.03% -0.87%]). CONCLUSION: The Wells scale used in primary care setting demonstrated a high degree of accuracy.

Pulmonary artery stenosis due to embryonal carcinoma with primary mediastinal location.

A 29-year old man was admitted to the intensive care unit after losing consciousness. On physical examination, a loud systolic murmur over the heart was found. Echocardiography revealed narrowing of pulmonary artery with high pressure gradient. Computed tomography of the chest revealed the presence of large tumour localised in the upper anterior mediastinum. Due to the risk of total closure of the pulmonary artery, interventional mediastinotomy was performed and diagnosis of carcinoma embryonale was established. Subsequent chemotherapy (BEP regimen) has brought regression of tumour and significant improvement in haemodynamic parameters (relief of pressure gradient in pulmonary artery). During the second surgery, the resection of all accessible tumour mass together with marginal resection of the right upper lobe was performed. No signs of cardiac or great vessels infiltration was found. Histopathologic examination revealed the necrotic masses and neoplastic foci diagnosed as teratoma immaturum. In a four-month follow-up the patient's condition remained good. The patient is still under the care of both oncological and cardiological specialists. Thus far he has not required further chemotherapy. Holter ECG monitoring revealed no arrhythmia, but the patient is still treated with mexiletine. The patient is planning to return to work.

[Normal D-dimer concentration in hospitalized patients with lung diseases]. / Czestosc prawidlowego stezenia D-dimerów u pacjentówhospitalizowanych z chorobami pluc.

INTRODUCTION: The use of D-dimer testing is an established part of the diagnosis of suspected pulmonary embolism (PE). However, in hospitalized patients many various factors might be responsible for increased D-dimer concentration and they could lower utility of D-dimer in exclusion of PE in such population. According to some published data, calculating the index D-dimer/fibrinogen could increase the specificity of D-dimer in the recognition of venous thromboembolism (VTE). The aim of the present study was to determine the frequency of normal D-dimer concentration in hospitalized patients with lung diseases in whom the differential diagnosis of PE is particularly difficult and to evaluate the utility of the index D-dimer/fibrinogen in subgroups of patients: with acute VTE and with lung cancer. MATERIAL AND METHODS: 619 consecutive patients aged 54.9 (± 15.4) hospitalized in reference pulmonary center were enrolled into observation. Among them, there were 96 (15%) patients with acute VTE, 65 (10%) with exacerbation of COPD and 172 (27%) with lung cancer. RESULTS: Mean D-dimer concentration (Vidas D-dimer New) was 1956 ± 3691 ng/ml and median value 842 (45-35 678) ng/ml. Normal D-dimer concentration (〈 500 ng/ml) was found in 225/523 (43%) without acute VTE. In 49% (32/65) patients with COPD and in 25% (43/172) patients with lung cancer D-dimer concentration was below 500 ng/ml as well. The index D-dimer/fibrinogen was significantly higher in acute VTE patients compared to lung cancer patients - 808 ± 688 and 289 ± 260 respectively, p 〈 0.001. CONCLUSIONS: Normal D-dimer concentration was found in more than 40% of patients with lung diseases hospitalized in reference pulmonary center. This observation could suggest higher than described in the literature utility of D-dimer measurement in exclusion of PE in such a population. The value of the index D-dimer/fibrinogen, which is significantly higher in acute VTE than in lung cancer requires further evaluation to establish its clinical utility.

Large Pericardial Effusion-Diagnostic and Therapeutic Options, with a Special Attention to the Role of Prolonged Pericardial Fluid Drainage.

BACKGROUND: Large pericardial effusion (LPE) is associated with high mortality. In patients with cardiac tamponade or with suspected bacterial etiology of pericardial effusion, urgent pericardial decompression is necessary. AIM: The aim of the present retrospective study was to assess the short-term results of pericardial decompression combined with prolonged drainage in LPE. MATERIAL: This study included consecutive patients with LPE who had been treated with pericardial fluid drainage between 2007 and 2017 in the National Tuberculosis and Lung Diseases Research Institute. METHODS: Echocardiographic examination was used to confirm LPE and the signs of cardiac tamponade. Pericardiocentesis or surgical decompression were combined with pericardial fluid (PF) drainage. Short-term effectiveness of therapy was defined as less than 5 mm of fluid behind the left ventricular posterior wall in echocardiography. RESULTS: The analysis included 74 patients treated with pericardial fluid drainage (33 female and 41 male), mean age 58 years, who underwent pericardial decompression. Out of 74 patients, 26 presented with cardiac tamponade symptoms. Pericardiocentesis was performed in 18 patients and pericardiotomy in 56 patients. Median PF drainage duration was 13 days. In 17 out of 25 patients with neoplastic PF, intrapericardial cisplatin therapy was implemented. In 4 out of 49 patients with non-malignant PF, purulent pericarditis was recognized and intrapericardial fibrinolysis was used. Short-term effectiveness of the therapy was obtained in all of patients. Non-infective complications were noted in 16% of patients and infective ones in 10%. CONCLUSION: Pericardial decompression combined with prolonged PF drainage was safe and efficient method of LPE treatment.

Treatment of acute respiratory failure in the course of COVID-19. Practical hints from the expert panel of the Assembly of Intensive Care and Rehabilitation of the Polish Respiratory Society.

In 2019, a pandemic began due to infection with a novel coronavirus, SARS-CoV-2. In many cases, this coronavirus leads to the development of the COVID-19 disease. Lung damage in the course of this disease often leads to acute hypoxic respiratory failure and may eventually lead to acute respiratory distress syndrome (ARDS). Respiratory failure as a result of COVID-19 can develop very quickly and a small percent of those infected will die because of it. There is currently no treatment for COVID-19, therefore the key therapeutic intervention centers around the symptomatic treatment of respiratory failure. The main therapeutic goal is to main-tain gas exchange, mainly oxygenation, at an appropriate level and prevent the intensification of changes in the lung parenchyma. Depending on the severity of hypoxemia different techniques can be used to improve oxygenation. Medical staff dealing with COVID-19 patients should be familiar with both, methods used to treat respiratory failure and the epidemiological risks arising from their use. In some patients, conventional (passive) oxygen therapy alone is sufficient. In patients with worsening respiratory failure high flow nasal oxygen therapy (HFNOT) may be effective. The continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV) methods can be used to a limited extent. With further disease progression, invasive ventilation must be used and in special situations, extracorporeal membrane oxygenation (ECMO) can also be administered. The authors of this article set themselves the goal of presenting the most current knowledge about the epidemiology and patho-physiology of respiratory failure in COVID-19, as well as the methods of its treatment. Given the dynamics of the developing pandemic, this is not an easy task as new scientific data is presented almost every day. However, we believe the knowledge contained in this study will help doctors care for patients with COVID-19. The main target audience of this study is not so much pneumonologists or intensivists who have extensive experience in the application of the techniques discussed here, but rather doctors of other specializations who must master new skills in order to help patients during the time of a pandemic.

Intrapericardial cisplatin combined with oral colchicine resulted in long term control of malignant pericardial effusion in the course of metastatic renal cancer.

Background Neoplastic pericardial effusion (NPE) represents a common cause of morbidity and mortality in patient with cancer. NPE presents frequently as cardiac tamponade, requiring urgent pericardiocentesis or pericardiotomy, with subsequent pericardial fluid drainage. Despite high effectiveness of such procedures, the recurrence of effusion is noted in 30- 60% of patients. Intrapericardial therapy with cisplatin was found to be effective in NPE due to lung and breast cancer. Its role in cardiac tamponade due to renal cancer is unknown. Case presentation We presented 82-year-old man with renal cancer who was admitted to the Intensive Care Unit because of threatening pericardial tamponade due to NPE . Urgent subxiphoid pericardiotomy was performed with subsequent evacuation of 1000ml of bloody fluid. On the inner surface of the pericardium several pink nodules were found. Histological examination revealed carcinoma clarocellulare. In view of the persistent high drainage of the pericardium, intrapericardial cisplatin therapy was performed. The first day after surgery colchicine 0.5 mg/day/po was also introduced. No side effects of this treatment were observed. The patient died 12- month later due to cancer progression and cachexia. No recurrence of pericardial effusion was observed. Conclusion This is the first case study demonstrating long-term efficacy and safety of intrapericardial cisplatin combined with oral colchicine in NPE due to metastatic renal cell carcinoma.

Accuracy of compression ultrasound in screening for deep venous thrombosis in acutely ill medical patients.

The value of vein ultrasonography for diagnosis of symptomatic deep vein thrombosis (DVT) is widely accepted. We are unaware of published data comparing ultrasonography with the "gold standard" of venography for DVT diagnosis in asymptomatic persons in the patient group of acutely ill medical patients. It was the objective of this study to evaluate sensitivity and specificity of compression ultrasound (CUS) examinations in the diagnosis of proximal and distal DVT in acutely ill medical patients [with congestive heart failure (NYHA class III and IV), exacerbations of respiratory disease, infectious disease, and inflammatory diseases] considered to be at moderate risk of venous thromboembolism (VTE). CUS examination was performed prior to ascending venography on day 6-15 of the hospital stay. Both investigations were done on the same day, each interpreted without knowledge of the other's result. Proximal and calf veins were separately evaluated. Technically satisfactory venography was obtained in 160 patients. In 12 of 160 patients (7.5%, 95% CI=[4.0%-12.7%]), venography confirmed the presence of DVT, all of which was asymptomatic. Proximal DVT was detected in five patients (3.1%, 95% CI=[1.0%-7.1%]) and distal DVT in seven patients (4.4%, 95% CI=[1.8%-8.8%]). CUS of proximal veins was technically satisfactory in all 160 patients and CUS of distal veins in 150 patients. In three of five patients with venographically proven proximal DVT, the diagnosis was confirmed by CUS (sensitivity 60%, 95%CI=[23%-88%]). In one patient, the CUS was false positive (specificity 99.4%, 95%CI=[96%-99%]). Positive and negative predictive values (PPV and NPV) of CUS in the diagnosis of proximal DVT were 75% (95%CI=[30%-95%]) and 98% (95% CI=[95%-99%]), respectively. In two of seven patients with venographically proven calf DVT, the diagnosis was confirmed by CUS (sensitivity 28.6%, 95%CI=[8%-64%]) and in two patients, CUS was false positive (specificity 98.6, 95%CI=[95%-99%]). PPV and NPV of CUS in diagnosis of distal DVT were 50% (95%CI=[15-85%]) and 96% (95% CI=[92%-98%]), respectively. In conclusion, CUS underestimates the incidence of proximal and distal DVT compared to contrast venography in acutely ill medical patients without thrombosis symptoms.

[The insufficiency of low molecular weight heparin (LMWH) prophylaxis in patients with hereditary antithrombin (AT) deficiency]. / Nieskutecznosc heparyn drobnoczasteczkowych w pierwotnej profilaktyce przeciwzakrzepowej u chorego z wrodzonym niedoborem antytrombiny (AT).

A 39 year old man with normal, stable blood pressure was admitted to the Cardio-Pulmonary Intensive Care Unit due to diagnosed spiral CT pulmonary embolism (PE) and deep venous thrombosis (DVT). In 1999, a hereditary antithrombin (AT) deficiency was confirmed in the presented case. In 2006, because of a knee injury, the patient was provided with a plaster cast and primary antithrombotic prophylaxis with low molecular weight heparin (LMWH) (80 mg of enoxaparin) was administered subcutaneously once a day (patient's weight was 80 kg). Despite prophylaxis PE and DVT occurred after 6 weeks of treatment. The patient was successfully treated with unfractioned heparin, repeated infusions of AT concentrate and oral anticoagulants (OA). Transient pulmonary hypertension documented by echocardiography and hemoptysis complicated course of PE. Secondary prophylaxis with OA, and INR maintenance between 2-3, was successfully continued.

Diffuse alveolar haemorrhage complicated by pulmonary embolism - problems with treatment.

Diffuse alveolar haemorrhage (DAH) refers to a clinical syndrome resulting from injury of the alveolar capillaries, arterioles and venules leading to red blood cel accumulation in the distal air spaces. The conditions associated with DAH and underlying disease determine the prognosis and the treatment regimen. The coexistence of DAH with venous thromboembolism (VTE) is a seroius problem for clinicians and poses a challenge in the therapeutic management. We describe a young patient who developed massive DAH in the course of anti-glomerular basement membrane (anti-GBM) disease (formerly called Goodpasture's syndrome) complicated by pulmonary embolism (PE).

[Thrombocytopenia probably heparin-induced in women with tumor of the heart and pulmonary embolism]. / Trombocytopenia prawdopodobnie poheparynowa (HIT) u chorej z guzem serca i zatorem tetnicy plucnej.

43 years old women with tumor of the right ventricle was admitted to ICU due to pulmonary embolism and suspicion for heparin-induced thrombocytopenia. Thrombocytopenia was successfully treated with Arixtra and the patient was qualified for the cardio surgery intervention. Heparin is widely used in treatment and prophylaxis of venous thromboembolism and other diseases. One of the most important adverse effect of treatment with heparin is heparin-inducted thrombocytopenia (HIT), which is one of the most frequent drug-induced, immune-mediated type of thrombocytopenia. If it is unrecognized is associated with significant morbidity and mortality. According to our knowledge this is first report of Arixtra usage in patient with suspicion of HIT in Poland.

Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension.

BACKGROUND: Right ventricular failure is a leading cause of death in patients with chronic pulmonary hypertension (PH). We checked whether detection of cardiac troponin T (cTnT), a specific marker of myocyte injury, could be useful in prognostic stratification of those patients. METHODS AND RESULTS: Initial evaluation of 56 clinically stable patients (age 41+/-15 years) with pulmonary arterial (51 patients) or inoperable chronic thromboembolic (5 patients) PH (mean pulmonary arterial pressure 60+/-18 mm Hg) included cTnT test, allowing detection of its serum levels > or =0.01 ng/mL [cTnT(+)]. cTnT was detectable in 8 of 56 (14%) patients (mean+/-SD, 0.034+/-0.022; range, 0.010 to 0.077 ng/mL). Despite similar pulmonary hemodynamics, they had higher heart rate (92+/-15 versus 76+/-14 bpm, P=0.004), lower mixed venous oxygen saturation (50+/-10% versus 57+/-9%, P=0.04), and higher serum N-terminal pro-B-type natriuretic peptide (4528+/-3170 versus 2054+/-2168 pg/mL, P=0.03) and walked less during the 6-minute walk test (298+/-132 versus 396+/-101 m, P=0.02). Cumulative survival estimated by Kaplan-Meier curves was significantly worse at 24 months in cTnT(+) compared with cTnT(-) (29% versus 81%, respectively, log-rank test P=0.001). Multivariate analysis revealed cTnT status (hazard ratio, 4.89; 95% CI, 1.18 to 20.29; P=0.03), 6-minute walk test (hazard ratio, 0.93 for each 10 m; P=0.01), and pulmonary vascular resistance (hazard ratio, 1.13; P=0.01) as independent markers of mortality. All 3 cTnT(+) patients who survived the follow-up period converted to cTnT(-) during treatment. CONCLUSIONS: Detectable cTnT is a so-far ignored independent marker of increased mortality risk in patients with chronic precapillary PH, supporting the role of progressive myocyte injury in the vicious circle leading to hemodynamic destabilization.

[Management of COPD: pulmonologists' adherence to Polish guidelines]. / Rozpoznawanie i leczenie POChP przez lekarzy specjalistów--zgodnosc z zaleceniami.

Literature data suggest that management of COPD in primary care and by specialists differ from national or international guidelines. Aim of this investigation was to evaluate routine management of COPD by Polish pulmonologists and to compare it to COPD guidelines of the Polish Society of Lung Diseases published in 1997 and updated in 2004. Questionnaire containing 33 questions was distributed to 800 participants of a national congress of the Society. Response rate was 10%. Term COPD is used by 95% of responders (R). For 73% of R COPD patients count for more than 20% of their consultations. Clinical signs of cor pulmonale are present in 10% and signs of respiratory failure in 10 to 20% of all patients. Patients with mild, moderate, severe and very severe disease represent respectively 18, 48, 24 and 10% of the total. Spirometry is performed to confirm diagnosis by 81% of R. However, bronchodilating test is performed in all patients only by 34% of R. 97% of R give antismoking advice to all patients. Only 6% of R are current smokers and 61% are life nonsmokers. Bronchodilating treatment is commonly prescribed. Most frequently prescribed drugs are: LABA (65% of patients) short acting anticholinergic (44%) and ICS (21%) of patients. ICS are over prescribed and systemic steroids are still chronically used in somewhat less than 20% of patients. 43% of R give systemic steroids to all patients during exacerbation of severe disease. Results of the study should be taken with caution. Low response rate suggest that only physicians interested in the treatment of COPD patients participated. A real life situation is probably worse than presented.

Intrapericardial fibrinolysis in purulent pericarditis-case report.

Purulent pericarditis (PP) continues to result in a very serious prognosis and high mortality. The most serious complication of pericarditis is constriction. Intrapericardial administration of fibrinolytic agents, although controversial, can prevent the development of constrictions. We present the case of a 63-year-old man with purulent inflammation of the right knee who was admitted to the intensive care unit (ICU) via emergency room orthopedic evaluation because of purulent pericarditis. Subxiphoid pericardiotomy was urgently performed, with 1200 ml of thick purulent fluid evacuated. As prevention for pericardial constriction, it was decided to administer fibrinolysis to the patient's pericardial cavity. Administration of streptokinase was complicated by the occurrence of a severe retrosternal pain and intrapericardial bleeding. Due to insufficiency of antibiotic therapy, 17 days after complicated fibrinolytic therapy with streptokinase, it was decided to administer 20 mg of r-tPA directly into the pericardium. In the following days, there remained a high drainage of purulent secretions. Fever up to 38 °C was still observed despite the use of antibiotics. Nine days after first administration of r-tPA, it was decided to apply the next dose. Daily drainage decreased from 50 to 20 ml in successive days. No fluid accumulation and symptoms and signs of constrictions were observed in clinical examinations as well as in echocardiography performed during 7 years follow-up after discharge.