Viruses in transplantology.

The 3 leading causes of death in patients after solid organ transplantation (SOT) include cardiovascular diseases, malignancies, and infections. According to our current understanding, the latter play the key role in the pathogenesis of atherosclerosis. Similarly, infections (mainly viral) are implicated in the pathogenesis of at least 20% of known neoplasms. In other words, the implications of acute and chronic infectious diseases in modern medicine, not only transplantology, are significant and ever­increasing. Immunosuppressive treatment impairs the immune function, which renders the patient more susceptible to infections. Furthermore, treatment of infections in immunocompromised patients poses a challenge and SOT. The current publication provides a brief summary of the key information provided in 20 lectures on viral infections in patients after SOT delivered during the 9th Practical Transplantology Course in Warsaw, Poland on September 15-16, 2017.

[Six-minute walk test in sarcoidosis patients with cardiac involvement]. / Test 6-minutowego chodu u chorych na sarkoidoze pluc z zajeciem serca.

INTRODUCTION: Cardiac involvement in sarcoidosis is of critical importance, due to the poor prognosis if this organ manifestation is left undiagnosed and untreated. The six-minute walk test (6 MWT) is a useful test to evaluate exercise tolerance of sarcoid patients. We aimed to assess the 6 MWT value in diagnosis, course and treatment monitoring of patients with cardiac sarcoidosis. MATERIAL AND METHODS: 47 patients were included: 22 with pulmonary sarcoidosis and cardiac involvement (13 women, 9 men), 25 with pulmonary sarcoidosis, with no changes in the heart (15 women, 10 men), and 18 healthy volunteers as controls (12 women, 6 men). Out of 22 patients with cardiac involvement 11 were treated for heart sarcoidosis with prednisone (9 pts - initial dose 60 mg daily and 2 pts - 40 mg daily). 11 pts in this group were not treated. In all patients sarcoidosis was confirmed histopatologically. Magnetic resonance imaging was used to diagnose involvement of the heart. In the studied groups we assessed: heart rate (HR), oxygen saturation, and distance in 6 MWT and Borg dyspnea score. RESULTS: Patients with cardiac sarcoidosis desaturated more during exercise (DSaO2max = 3.5 ± 3.2 vs. 0.38 ± 0.69; p = 0.004) and had a lower increase of HR in first minute during the 6 MWT (DHR1 = 21.81 ± 11.72 vs. 50.61 ± 12.35; p = 0.0001) when compared to healthy subjects. Significantly lower increase of HR in first minute of 6 MWT was observed in patients with cardiac sarcoidosis when compared to patients with pulmonary sarcoidosis with no cardiac involvement (DHR1 = 21.81 ± 11.72 vs. 38.8 ± 18.17, p = 0.01). After introduction of treatment in sarcoidosis group, significantly higher (p = 0.02) increase of HR in first minute of 6 MWT as compared to baseline test was observed. CONCLUSIONS: The six-minute walk test is useful in diagnosing cardiac involvement in sarcoidosis. The increase in HR during exercise and decrease degree of desaturation were a good predictors of the response to therapy.

[Markers of fibrosis and inflammation in exhaled breath condensate (EBC) and bronchoalveolar lavage fluid (BALF) of patients with pulmonary sarcoidosis -- a pilot study]. / Markery wlóknienia i zapalenia w kondensacie powietrza wydychanego (EBC) oraz w plynie z plukania oskrzelowo-pecherzykowego (BALF) u chorych na sarkoidoze pluc - badanie pilotazowe.

INTRODUCTION: Sarcoidosis is a disease of unknown etiology. Little is known of predictive factors of fibrosis. It was suggested that PAI-1, uPA, TGF-beta1, VEGF, IL-8, TNF-alpha influence this process. AIMS: To assess airway inflammatory and fibrosis markers in EBC in sarcoidosis and the effect of fiberoptic bronchoscopy (FOB), bronchoalveolar lavage fluid (BALF), transbronchial lung biopsy (TBLB) and bronchial mucosa membrane biopsy on their production in the airways. MATERIAL AND METHODS: The study group consisted of 11 patients (5 women, 6 men; mean age 40 +/- 9 yrs, mean +/- SD) with sarcoidosis stage I-III. PAI-1 (ng/ml), uPA (ng/ml), TGF-beta1 (pg/ml), VEGF (pg/ml), IL-8 (pg/ml), TNF-alpha (pg/ml) levels were measured in BALF and EBC collected before and 48 hours after FOB. RESULTS: No significant changes in EBC levels of VEGF, PAI-1, TGF-beta1, TNF-alpha (respectively: 8.02 +/- 4.97 pg/ml; 1.1 +/- 1.2 ng/ml; 2909.7 +/- 206.6 pg/ml; 10.7 +/- 19.9 pg/ml) after FOB were observed when compared to baseline. In contrast, IL-8 concentration in EBC (pg/ml) decreased after FOB (0.073 +/- 0.13 v. 0.061 +/- 0.1, p = 0.006) and was significantly lower than in BALF (BALF 0.95 +/- 0.62, p < 0.05). Also, mean level of VEGF was higher in BALF than in EBC both pre- and post- FOB (BALF 66.38 +/- 36.95, EBC pre-FOB 6.75 +/- 3.67 and EBC post-FOB 8.02 +/- 4.97). Significant relationship between TNF-alpha in post-FOB EBC and BALF was also shown (b = 0.63, p = 0.04). CONCLUSIONS: FOB does not significantly affect levels of airway inflammation and fibrosis markers present in EBC before and after FOB; they were also comparable to the concentrations marked by BALF. The lack of correlation between markers levels in EBC and BALF indicates that these methods are not equivalent. Due to repeatibility, and less invasive, simple method of EBC test it seems reasonable to continue the research on the larger number of patients.

Manageability of acute severe heart failure complicated with left ventricular thrombosis during therapy for breast cancer.

Trastuzumab-related cardiac dysfunction may be manageable and completely reversible with suitable cardiac medication, allowing optimal breast cancer treatment to continue. We present the case of a 42-year-old woman who developed severe systolic left ventricular failure with impaired contractility of the right ventricle, pulmonary hypertension, and clots in the left ventricular cavity during adjuvant treatment for breast cancer. The patient was initially diagnosed with early breast cancer and underwent surgery on her left breast. She received 6 cycles of anthracycline chemotherapy followed by radiation therapy in the left breast area, then 5 cycles of trastuzumab. After the fifth cycle of trastuzumab, she experienced dyspnoea and leg edema. Fluid was detected in the pleural cavities but no lung metastases were identified. Echocardiography was performed, revealing a severely reduced left ventricular ejection fraction (10%) with impaired contractility of the right ventricle and pulmonary hypertension. Standard medication for heart failure resulted in complete recovery of normal systolic and diastolic function of the left and right ventricles. The combination of low molecular weight heparin and acetylsalicylic acid completely resolved the thrombotic complications. The patient regained her full range of social, occupational, and family activities. This case study is the first to demonstrate the manageability and reversibility of trastuzumab-related cardiac complications in a patient who had developed severe heart failure complicated with left ventricular thrombosis during sequential anthracycline and trastuzumab therapy for breast cancer. The findings contradict other opinions that trastuzumab-related acute heart failure is analogous to stunning or hibernation and recovers without specific cardiac treatment.

[Metabolic abnormalities in obstructive sleep apnea patients]. / Zaburzenia metaboliczne u chorych na obturacyjny bezdech senny.

INTRODUCTION: Obstructive sleep apnea (OSA) is a well-recognized risk factor of cardiovascular disorders and is related to metabolic syndrome. The aim of this study was to evaluate the effect of BMI and AHI/RDI on metabolic disturbances in patients suspected of OSA. MATERIAL AND METHODS: Ninety-nine patients referred with suspected OSA underwent standard polysomnography or limited sleep study. AHI/RDI > or = 10/hour was considered relevant for OSA diagnosis. Subjects with AHI/RDI < 10 were considered as controls. We assessed apnea-hypopnea index or respiratory disturbances index (AHI/RDI), Epworth sleepiness scale (ESS), body mass index (BMI), C-reactive protein (CRP, mg/l), glycosylated haemoglobin (HbA1c, %), fasting serum total cholesterol, HDL-, LDL-cholesterol, triglycerides (TG), glucose (G), insulin (INS, IU/ml) and HOMA index. RESULTS: Data are presented as mean +/- SD or median (interquartile range) for parametric and nonparametric data respectively. Twenty-two patients were included as controls (age 51.8 +/- 10 vs. 55 +/- 11 in OSA; p = NS). AHI/RDI in the OSA group was 23 (16-31.3) and 7 (3.8-8.1) in controls (p < 0.001). BMI in OSA 32.2 +/- 5.8 vs. 30.4 +/- 4.6 in controls (p = NS). Patients with OSA had higher TG (160 +/- 75.9 vs. 130.2 +/- 51.9 mg/dl, p = 0.046), G (5.04 +/- 0.6 vs. 4.47 +/- 0.6, p = 0.0037), HOMA (2.31 +/- 1.5 vs. 1.85 +/- 1.7, p = 0.046). G correlated best with AHI/RDI (p < 0.001, r = 0.41). Significant differences were observed in OSA patients between obese (51 pts, BMI 35.2 +/- 4.8) and non-obese (26 pts, BMI 26.61 +/- 1.9) pts in: HDL-cholesterol (50.8 +/- 13.2 vs. 60.9 +/- 18.4 mg/dl; p = 0.02), TG (178.7 +/- 69.9 vs. 124 +/- 75.3 mg/dl, p < 0.001), G (5.15 +/- 0.7 vs. 4.8 +/- 0.5 mmol/l, p = 0.01), INS (11.7 +/- 5.9 vs. 6.57 +/- 4.7, p < 0.001), HOMA (2.7 +/- 1.4 vs. 1.4 +/- 1.2, p < 0.001), HbA(1c) (5.89 +/- 0.9 vs. 5.4 +/- 0.8, p = 0.03), CRP (2.2 +/- 2.9 vs. 1.09 +/- 1.2, p = 0.01). CONCLUSIONS: Our findings support the results of previous studies showing the influence of OSA alone on metabolic disturbances. However, BMI has major impact on metabolic variables.

[Six-minute walk test in obstructive sleep apnoea]. / Test 6-minutowego chodu u chorych na obturacyjny bezdech senny.

INTRODUCTION: The aim of this study was to assess results of 6MWT in non-selected group of obstructive sleep apnoea (OSA) patients. In healthy adult subjects 6-minute walking distance (6MWD) range from 400 to 700 m. Obesity, the main symptom of OSA, is one of the factors associated with reduction of 6MWD (another common factors: older age, shorter height, female sex, pulmonary, cardiovascular and musculoskeletal diseases). MATERIAL AND METHODS: Subjects completed sleep questionnaire and Epworth sleepiness scale before sleep studies (full polysomnography [PSG] or PolyMesam study [PM]). Consecutive OSA subjects (AHI/RDI >10, Epworth score > 9 points) were evaluated. The 6MWT, chest X-ray, spirometry, arterial blood gases, ECG, blood morphology and biochemistry were performed during trial treatment with autoCPAP. RESULTS: We studied 151 subjects (119 males - 78.8% and 32 females - 21.2%), mean age 53.4 +/- 10.5 years. Subjects were obese - BMI = 35.7 +/- 6.2 kg/m(2) and presented severe OSA - AHI/RDI = 42.4 +/- 23.2. To assess relations between 6MWD and AHI/RDI, BMI, age and concomitant diseases we divided subjects in two groups: 1(st) with 6MWD > or = lower limit of normal (LLN) (123 pts; 81.5%) and 2(nd) with 6MWD < LLN (28 pts; 18.5%). Significant differences between groups were found for BMI, FVC (% of predicted) and Borg dyspnea scale before and after 6MWT. In multiple linear regression analysis we found significant correlation between 6MWD and BMI (beta = 0.41, p < 0.0001) and arterial hypertension (beta = -0.16, p = 0.04). Females had significantly shorter 6MWD than males (401.1 +/- 83.6 m and 451.8 +/- 107 m, respectively; p = 0.01). Difference was significant after adjustment for BMI and age (analysis of covariance) - R = 0.61, R2 = 0.38 (p < 0.0001). CONCLUSIONS: BMI, female sex, arterial hypertension and lower FVC (% of predicted) were related to shorter 6-minute walking distance in OSA patients.

[Failure of uvulopalatopharyngoplasty (UPPP) in severe obstructive sleep apnoea (OSA)]. / Uwulopalatofaryngoplastyka (UPPP) jako zabieg nieskuteczny w leczeniu ciezkiego obturacyjnego bezdechu sennego (OBS).

INTRODUCTION: Uvulopalatopharyngoplasty (UPPP) is the most frequent surgical procedure in obstructive sleep apnoea (OSA) treatment. The aim of this study was to assess effects of UPPP in OSA subjects admitted to our Sleep Laboratory. MATERIAL AND METHODS: We studied 22 mostly obese males (mean BMI = 33.1 +/- 4 kg/m(2)) in mean age 51.7 +/- 9.7 years. Polysomnography or polygraphy (Poly-Mesam) was performed 28.5 +/- 30.5 month after UPPP. RESULTS: Sleep studies after UPPP revealed severe OSA in most of the patients - mean AHI/RDI = 53 +/- 33.2, mean overnight SaO(2) = 88.1 +/- 5.3%. Subjects spent near half night in desaturation below 90% (T90 = 46.8 +/- 33.8%) and presented daytime somnolence (Epworth score: 14.3 +/- 4.8 points). Only in 3 subjects (13.6%), UPPP was successful (AHI/RDI < or = 10). CONCLUSIONS: Our study confirmed previous data that UPPP is ineffective in majority of obese subjects with severe OSA.

[Nocturia in obstructive sleep apnoea (OSA)]. / Nykturia u chorych na obturacyjny bezdech senny (OBS).

INTRODUCTION: Nocturia (two or more urinations per night) is a common symptom in OSA subjects. Higher secretion of atrial natriuretic peptide, increased intra-abdominal pressure, diuretics, diabetes, excessive fluid intake, awakenings are responsible for nocturnal urination. The aim of this study was to evaluate incidence of nocturia in moderate and severe OSA. MATERIAL AND METHODS: We studied 171 consecutive OSA patients (135 males and 36 females) - means: age - 53.6 +/- +/- 10.8 years, AHI/RDI - 43.6 +/- 23.2, BMI - 35.8 +/- 6.3 kg/m(2). RESULTS: To assess relations between nocturia and AHI/RDI, overnight saturation, BMI and daytime sleepiness we divided subjects in two groups: 1(st) - without nocturia - 60 pts; 35.1% (group N-) and 2(nd) - with nocturia - 111 pts; 64.9% (group N+). Group N+ presented with higher AHI/RDI, 48 +/- 22.8 vs. 35.4 +/- 21.7 (p = 0.0006), higher BMI, 36.8 +/- 6.5 vs. 34 +/- 5.5 kg/m(2) (p = 0.004), lower mean overnight SaO(2), 88.6 +/- 5.6 vs. 90.4 +/- 4.3% (p = 0.03) and daytime sleepiness, Epworth score - 14.4 +/- 5.1 vs. 11.3 +/- 5.5 points (p = 0.0002). Multiple linear regression analysis revealed significant correlation between nocturia and Epworth sleepiness score (beta = 0.26, p = 0.0009), coronary artery disease (beta = 0.23, p = 0.004) and AHI/RDI (beta = 0.21, p = 0.04). CONCLUSIONS: Nocturia is frequent in OSA patients (64.9%). Nocturnal urination was related to severity of OSA, excessive daytime sleepiness and coronary artery disease.

[A 30-year history of a patient with bronchiectasis]. / Trzydziestoletnia obserwacja chorego na rozstrzenie oskrzeli.

We describe the long-term course of a patient with bronchiectasis. Sequential chest X-rays, symptoms, spirometry and blood gas analysis obtained during the observation period showed gradual progression. Conservative medical management was implemented in the treatment of described patient. Bronchiectasis is a disease characterised by irreversible dilation of airways, repeated respiratory infections, productive cough and dyspnoea caused by a variety of factors. The foundations of therapy include administration of antibiotics, treatment of underlying conditions, bronchial hygiene and rarely--surgery. Survival in bronchiectasis depends on presence of comorbidities and complications of lung disease.

[Gastroesophageal reflux disease (GERD) in patients with obstructive sleep apnoea syndrome (OSAS)]. / Refluks zoladkowo-przelykowy u chorych na obturacyjny bezdech senny (OBS).

Gastroesophageal reflux disease (GERD) is a common cause of chronic cough, heartburn, epigastric or retrosternal discomfort, chest pain and abdominal pain or esophagitis. Our patients with OSAS seldom manifest GERD symptoms. We suspected that obesity and high pressure in abdominal cavity may induce acid gastroesophageal reflux in these patients. The aim of the study was to test the hypothesis that obesity, cigarettes smoking or ventilatory and gas exchange abnormalities provoke GERD. We studied 21 consecutive patients with severe OSAS (mean AHI 44.9+/-23.8) before CPAP treatment, all without GERD clinical symptoms. Standard polysomnography, gastroscopy and 24-h oesophageal pH monitoring was performed. There were 6 females, 15 males, mean age 57+/-9 years, mean BMI 38+/-6 kg/m2. All patients presented with normal spirometric and gas exchange values (mean VC 3.64+/-1.23 1, 90% of normal, mean FEV1 2.61+/-0.95 1, 83% of normal, mean FEV1%VC 72%, mean PaO2 68.1+/-7.7 mmHg, mean PaCO2 40.8+/-5.8 mmHg, mean pH 7.42+/-0.02). GERD was diagnosed in 14 patients. Patients with GERD were younger, more often were cigarettes smokers (5/14). We did not fi nd statistically significant differences between severity of OSAS, BMI, ventilatory or gas exchange parameters and GERD.

[Central sleep apnoea (CSA) in male with heart failure]. / Centralny bezdech senny (CBS) u chorego z niewydolnoscia serca.

We studied 44-year old man with heart failure (ejection fraction -25%). Obesity, arterial hypertension, snoring and excessive daytime sleepiness suggested concomitant obstructive sleep apnoea. Limited polysomnography with Polymesam revealed typical Cheyne-Stokes respiration with mainly central apnoeas (RDI=48/hour). We did not find any obstructive episodes during sleep study. Patient responded to CPAP therapy and apnoea hypopnoe index decreased to 12/hour on 8 mbar pressure.