Prevalence and risk factors for Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT) during Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)

Introduction: COPD patients are at high risk for PE and DVT due to immobility, inflammation, comorbidities.Prevalence of PE during AECOPD is uncertain and often under-diagnosed.Material and methods: Single-center, prospective, an observational trial of 100 hospitalized patients with AECOPD, diagnosed according to GOLD criteria, 40–75 years, stratified according to airflow limitation (I–IV), divided into subgroups (PE-diagnosed/non-PE and with known/ undetermined exacerbation etiology).Investigations: clinical risk assessment, electrocardiogram (ECG), laboratory, spirometry, gas-analysis, D-dimer (DD), chest X-ray, thoracic ultrasonography (TUS), Doppler-ultrasonography of deep-veins of lower-extremities (DULE). Patients with high DD and DVT or high DD and abnormal TUS underwent computed-tomography pulmonary-angiography (CTPA).Results: PE was diagnosed in 26 (26.0%), DVT in 5 (5.0%) of hospitalized AECOPD patients. There was a positive correlation between COPD-severity and PE. Frequencies of PE in GOLD-stages I, IV, were 0 (0.0%), 3 (11.5%), 8 (30.7%), 15 (57.7%) respectively. Patients with pleuritic chest-pain, TUS abnormality, phlebitis and high DD were more likely to develop PE. Localization was subsegmental in 9 (34.6%), in one of the main pulmonary arteries 7 (26.9%), lobar and interlobar arteries in 10 (38.5%). DD was significantly higher among patients with PE than those without (3.34 ± 1.1 μg/mL vs. 2.2 ± 0.8μg/mL, P < 0.0001). There was positive correlation between the presence of PE and elevated DD > 2.0 μg/mL (P = 0.02). There was no statistically significant difference between patients with PE and without, according to age, gender and comorbidities (P > 0.05). Immobility and obesity were significantly higher among PE patients, P = 0.032 and P < 0.0001 respectively.Conclusion: AECOPD associated with pleuritic chest pain, immobility, high DD, should be considered for PE. Chest-ultrasound, as a low-cost and safe procedure, can be a very helpful investigation

Clinical features of a young patient with COVID-19 presented with ARDS and severe thrombocytopenia

Case report of a 33-year-old male SARS-CoV-2 positive patient admitted to hospital because of hemoptysis, dyspnea, fever, oxygen saturation of 60%, hypoxemia, elevated C-reactive protein (CRP). The patient was not vaccinated and it was his first infection with the virus. The symptoms started 10 days before with headache, fever, and cough. Chest radiography on hospital admission detected diffuse interstitial pneumonia in both lungs. Initial CT (Computed Tomography) presented extensive lung involvement with bilateral wide areas of consolidation with air bronchogram, the non-consolidated area showing patchy ground glass infiltration. The patient was hospitalized in ICU (Intensive Care Unit), oxygen support was started immediately with non-invasive ventilation (NIV), CPAP (Continuous Positive Airway Pressure) mode, FiO2 (Fraction of inspired Oxygen) 100%, PEEP (Positive end-expiratory pressure) 8, and the saturation started to increase. Therapy consisted of parenteral antibiotic, low-molecular weight heparin (LMWH) in prophylactic doses, pulsed dose of corticosteroid (methylprednisolone), Remdesivir, tocilizumab (Actemra), albumin, protein-pump inhibitor, antipyretics, fluids, physical therapy. Microbiology results from sputum detected MRSA (methicillin-resistant Staphylococcus aureus) and therapy with Vancomycin was started according to recommendations. After three days of vancomycin therapy, the patient manifested profuse epistaxis and tamponade was necessary. Hemostasis result was normal, but severe thrombocytopenia was noticed in the blood count. Platelets and plasma were administered and the bleeding stopped. Vancomycin was replaced with Linezolid. In the next days of follow up, the platelets increased, and the corticosteroid dose was slowly reduced. During the treatment as the health status of the patient improved, the CPAP therapy was replaced with routine oxygen support, gradually lowering the oxygen flow until saturation of 94% was achieved at ambient air. The COVID-19 pandemic is still evolving and the medical fraternity is posed with a huge challenge. COVID-19 is primary a respiratory viral infection, but the virus can affect many organs and systems, presenting various signs, symptoms and outcomes

Cachexia in Chronic Obstructive Pulmonary Disease (COPD)

The prevalence and mortality of chronic obstructive pulmonary disease (COPD) in elderly patients are increasing worldwide. Low body mass index (BMI) is a well-known prognostic factor for COPD. Cachexia and muscle wasting is well recognized as common and partly reversible features of COPD, adversely affecting disease progression and prognosis. There is considerable heterogenicity in the rate of lung function decline in COPD, the determinants of which are largely unknown. Observational studies in COPD indicate that low BMI is associated with worse outcomes, and overweight/obesity has a protective effect - the so-called "obesity paradox". We aimed to determine the relationship between BMI and the rate of FEV1 decline. The design is a cross-sectional study, including 220 patients with stable COPD as investigated group (IG), aged 40-75 years and 58 non-COPD subjects, matched by gender, age, BMI, smoking-status, as control group (CG). All study subjects underwent pulmonary evaluation (dyspnea severity assessment, baseline and postbronchodilator spirometry, gas analyses), BMI measurement. We analyzed BMI in 4 categories: BMI-I (< 18.5 or < 20 kg/m2), BMI-II (18.5 or 20 to < 25 kg/m2), BMI-III (25 to < 29 or < 30 kg/m2) and BMI-IV (≥29 or ≥ 30 kg/m2). The analysis indicated incorrect distribution of frequencies for BMI (kg/m²) values for Shapiro-Wilk W=0.9746; p=0.00007, which is why appropriate non-parameter statistical tests were applied to the analyses. For p<0.05, no significant difference was established between the four IG subgroups in relation to the height of the BMI (Kruskal-Wallis H test: p=0.0291). Additional analysis in both groups indicated an average BMI of 25.4±3.8 kg/m² with a min/max of 17.6 /35.5 kg/m² in IG vs. 26.2±2.5 kg/m² with a min/max of 19.4 /33.2 kg/m² in CG. 50% of IG participants were less than 25.3kg/m² for Median IQR=25.3 (22.9-27.4), and in 50% of CG it was Median IQR=29.2. For p<0.05, the analysis indicated a significant association between the nutrition of subjects and the subgroup (GOLD 1→ GOLD 4) to which they belonged (Fisher Freeman Halton test: p=0.023). With decline of FEV1, BMI also declined. Analysis between the two (IG/CG) groups indicated that, for p<0.05, there is a significant association between nutrition and the group to which the respondents belong (Pearson Chi-square test: X2=8,691; df=2; p=0.0129). CG respondents were 2,648 times more frequent obese compared to IG [OR=2.65 (1.37–5.13) 95% CI]. In this review, recent insights are presented in the frequency of cachexia in COPD. In mild to moderate COPD, higher BMI was associated with a less rapid decline of FEV1 in male patients whereas this association was minimal in female patients. This gender-specific BMI effect was independent of COPD severity and smoking status. These novel findings support the obesity para�dox in COPD: compared to normal BMI, low BMI is a risk factor for accelerated lung function decline, whilst high BMI has a protective effect. The relationship may be due to common but as-of-yet unknown causative factors; further investigation into which may reveal novel endotypes or targets for therapeutic intervention

Diabetes mellitus type 2 (T2D) as a comorbidity of chronic obstructive pulmonary disease (COPD)

We aimed to investigate the association between COPD and T2D and the relation to the severity of airflow limitation. Cross-sectional study including 120 patients with initially diagnosed COPD, aged 40 to 75 years and 60 nonCOPD subjects matched by age, smoking status, body mass index, as controls. All study participants underwent anthropometric measurements, fasting blood sugar (FBS), oral glucose tolerance test (OGTT) (performed in patients with fasting blood sugar level 5.6- 6.1mmol/L (measured two times), lipid profile, CRP, pulmonary evaluation (dyspnea severity assessment, baseline and post-bronchodilator spirometry, gas analyses, chest X-ray). Results presented statistically significant difference in presence of T2D in COPD patients compared to controls (45.0% vs 20.0%; P=0.0011). According to the GOLD classification, the frequencies of T2D in COPD patients were categorized in stages I, II, III, IV (25.0%, 43.3%, 52.5%, 58.3%, respectively), and according to combined assessment test in A, B, C, D (29.2%, 37.5%, 35.0%, 41.7% respectively). In GOLD 2 stage the risk for T2D was 2.3 times higher than GOLD1. COPD patients with T2D presented significant association with pulmonary function. FBS was higher in COPD than controls (8.4±1.1mmol/L vs 4.9±2.1mmol/L) with statistical significance (p<0.0001), but HDL was lower in COPD than controls (39.1±6.4mg/dl vs 49.6±3.9mg/dl) with statistical significance (p<0.0001).We found higher prevalence of T2D in patients with COPD even in early COPD stages compared to nonCOPD. Our findings suggest multidisciplinary approach in COPD patients for prevention, diagnosis and early start of treatment

Prevalence and risk factors for Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT) during Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)

Introduction: COPD patients are at high risk for PE and DVT due to immobility, inflammation, comorbidities. Prevalence of PE during AECOPD is uncertain and often under-diagnosed. Material and methods: Single-center, prospective, an observational trial of 100 hospitalized patients with AECOPD, diagnosed according to GOLD criteria, 40–75 years, stratified according to airflow limitation (I–IV), divided into subgroups (PE-diagnosed/non-PE and with known/ undetermined exacerbation etiology). Investigations: clinical risk assessment, electrocardiogram (ECG), laboratory, spirometry, gas-analysis, D-dimer (DD), chest X-ray, thoracic ultrasonography (TUS), Doppler-ultrasonography of deep-veins of lower-extremities (DULE). Patients with high DD and DVT or high DD and abnormal TUS underwent computed-tomography pulmonary-angiography (CTPA). Results: PE was diagnosed in 26 (26.0%), DVT in 5 (5.0%) of hospitalized AECOPD patients. There was a positive correlation between COPD-severity and PE. Frequencies of PE in GOLD-stages I, IV, were 0 (0.0%), 3 (11.5%), 8 (30.7%), 15 (57.7%) respectively. Patients with pleuritic chest-pain, TUS abnormality, phlebitis and high DD were more likely to develop PE. Localization was subsegmental in 9 (34.6%), in one of the main pulmonary arteries 7 (26.9%), lobar and interlobar arteries in 10 (38.5%). DD was significantly higher among patients with PE than those without (3.34 ± 1.1 μg/mL vs. 2.2 ± 0.8μg/mL, P 2.0 μg/mL (P = 0.02). There was no statistically significant difference between patients with PE and without, according to age, gender and comorbidities (P > 0.05). Immobility and obesity were significantly higher among PE patients, P = 0.032 and P < 0.0001 respectively. Conclusion: AECOPD associated with pleuritic chest pain, immobility, high DD, should be considered for PE. Chest-ultrasound, as a low-cost and safe procedure, can be a very helpful investigation. Keywords COPD, D-dimer, pulmonary embolism, deep vein thrombosis, chest ultrasonography, lung computed tomography angiograph

Is semaglutide superior that liraglutide in patients with type2 diabetes on insulin therapy – case presentation

Introduction Type 2 diabetes (T2DM) is a chronic and progressive disease associated with microvascular and macrovascular complications leading to increased morbidity and mortality. Insulin remains the cornerstone therapy for longer-duration T2DM and b-cell failure. T2DM is a complex disorder that requires individualized treatment strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of multifactorial T2DM medications that have been shown to improve numerous risk factors for diabetes-related complications, including glycemic control, reduction in body weight and a low risk of hypoglycaemia. Case Presentation A 65-year old obese male presented to the outpatient clinic of Endocrinology, 8th September City General Hospital, Skopje for a regular checkup. He has T2DM for a long time and the last 10-15 years was switch on insulin therapy – at the moment was on premix insulin – Insulin Aspart and OAD. He was complaining of variation of glycaemia (5.0-16.5 mmol/l), felling a little bit thirsty, hungry and without energy. He has arterial hypertension and dyslipidemia (medications was prescribe from cardiologist) but could not tolerated any statins. He is a nonsmoker, with two children and retired. Investigations Initial investigation showed HgA1c 55.2 mmol/mol, FPG 9.1 mmol/l, elevated cholesterol (cho -6.8 mmol/l), low density (LDL – 2.8 mmol/l) triglyceride ( Tg - 2.7 mmol/l). His renal and liver functional test were within normal limits. The tests for thyroid functional were also normal. He was 180centimetar tall, 149kg weight and his body mass index (BMI) was 46.0. Echotomography showed steatotic liver, echocardiography and ophthalmic tests were in normal range for his age. Treatment The patient was overweight, hasn’t achieved the optimal glycemic control even though he was on insulin therapy and one of his biggest concerns was his weight , so the medical team decided to add Liraglutide on his diabetes therapy with gradual titration of the dose ( Liraglutide - was started at 0.6mg daily subcutaneously for 1 week and then increased from 1.2 mg to 1.8mg daily). Also he was educated about titration of the dose of the insulin therapy together with additional lifestyle modifications Because of the positive effect from the therapy with once daily GLP-1 RA, and because we wanted to continue with weight loss, but at the same time reduce the everyday subcutaneous therapy we decide to change Sol Liraglutide 1.8mg per day with Sol Semaglutide starting with 0.25mg once a week for 1 month and then titrating the doses till 1mg per week, together with reducing the insulin therapy, metformin 2000mg daily, balance food and physical activity (Table 1). Discussion The objective of this case report was to demonstrate the efficacy and safety of onceweekly semaglutide vs once daily GLP-1 RAs in patient with T2DM inadequately controlled on insulin therapy (± OADs). In our case report, we observed that once-weekly semaglutide 1 mg was dominant compared with once-daily liraglutide 1.8 mg. In this case report, once-weekly semaglutide 1.0 mg was the most clinically effective GLP-1 RA for achieving glycemic targets and reducing HbA1c, FPG, and body weight in patient who is receiving insulin therapy. In patients with T2DM inadequately controlled with insulin therapy, semaglutide provided superior improvements in mean HbA1c, FPG, and superior weight loss compared with liraglutide. Conclusion Semaglutide, administered subcutaneously once weekly, provided superior glycemic control and body weight reductions compared with other GLP-1 RA in patient with T2DM receiving insulin therapy. Therefore, it is likely that once-weekly semaglutide will not increase the risk of hypoglycemia when added to insulin therapy. The reasons for switching to semaglutide from liraglutide included a need to reduce HbA1c or weight further, decreased frequency of administration and cardiovascular protection. In addition, significant weight loss was observed with both doses of semaglutide vs liraglutide

Alpha-1 antitrypsin deficiency (AATD) in a young female patient

Introduction The alpha-1 antitrypsin deficiency (AATD) is a hereditary autosomal codominant disease. The phenotype Pi ZZ is associated more frequently with pulmonary disease and is responsible for the presence of emphysema early in life, particularly in smokers. Generally, AATD is suspected in young patients with pulmonary emphysema or chronic obstructive pulmonary disease (COPD). Patients often suffer from diagnostic gaps and are misdiagnosed with chronic obstructive pulmonary disease (COPD), asthma, and airway hyper-reactivity (AHR), as AATD may present with nonspecific respiratory symptoms. AATD is most common in white people, and it most frequently affects the lungs and liver. In the lungs, the most common manifestation is early-onset (patients in their 30s and 40s) pan acinar emphysema most pronounced in the lung bases. However, diffuse or upper lobe emphysema can occur, as can bronchiectasis. The most frequently described symptoms include dyspnea, wheezing and cough. Pulmonary function testing shows findings consistent with COPD; however, bronchodilator responsiveness may be seen and may be labelled as asthma. Case presentation We describe a case of a 40-year-old Caucasian female patient, admitted to hospital because of dyspnea, malaise, cough. Symptoms started one year ago, after mild SARS-COV 2 infection. Chest X-ray during the acute illness described emphysema, with flattened diaphragm, and no signs of consolidation. According to history she was a non-smoker, office worker, with negative family history of respiratory or liver illness. She never used any regular therapy before, no comorbid diseases and denied frequent respiratory infections during childhood. Chest computer tomography (CT) presented pan acinar emphysema most pronounced in the lung bases. Post bronchodilator spirometry revealed forced expiratory volume in 1st second (FEV1) 54%, and forced vital capacity (FVC) 84%, with FEV1/FVC=0.64. Routine biochemistry laboratory was normal. Gas analyses noted respiratory failure type 1 (partial) with hypoxemia partial oxygen pressure 8.1kPa, hypocapnia because of hyperventilation with partial carbo dioxide pressure 4.1kPa, and oxygen saturation 92%. Echocardiography without any findings of right heart failure, normal systolic pulmonary arterial pressure (sPAP). Abdominal ultrasound without pathological findings, no liver disease detected. According to CT finding the patient was sent to the Institute for clinical immunology and genetic disorders where the serum value of alpha-1 antitrypsin was measured. The value was 0,2 micromoles /L (reference value 5-6 micromole /L). The patient was prescribed inhaled therapy of long acting anticholinergic, short acting beta-2 agonist. She was also suggested therapy with intravenous human alpha 1-proteinase inhibitor (AAT augmentation therapy). Conclusion It is never too late to suspect AATD, especially in a patient with an unusual medical history. In recent years, evidence is beginning to emerge that there may be value in identifying and treating patients who do not already have deterioration of functional parameters. The Alpha-1 Foundation recommendations for the diagnosis and management of AATD in adult patients indicate that treatment should be provided for patients with FEV1 between 30 and 65%. It may be useful to evaluate and treat patients based on clinical symptoms, even outside the established parameters, in particular cases

Case report: Primary hyperparathyroidism due to mediastinal parathyroid adenoma, our pint of view

Primary hyperparathyroidism is defined by elevated parathyroid hormone and calcium levels, most usually caused by a parathyroid adenoma. Parathyroid adenomas are most commonly detected in the neck or an ectopic site, seldom in the mediastinum. The parathyroid adenoma can occur in ectopic locations such as the mediastinum, thymus, or retro oesophagal area in 6-16% of cases. We presented the example of a 73-year-old woman who was found to have hypercalcemia during a regular test. The patient’s serum calcium (3.11 mmol/L), alkaline phosphatase (162 U/L), parathyroid hormone (PTH: 379 pg/mL) and creatinine (111.6 umol/L) levels were higher than the reference values. A chest computerized tomography scan revealed an anterior mediastinal mass, and nuclear scintigraphy revealed functioning parathyroid tissue in the mediastinum. The mediastinal parathyroid adenoma was effectively removed surgically, and the PTH level began to fall. Any hypercalcemia and high PTH levels in the absence of a parathyroid adenoma in the neck should prompt clinicians to look for ectopic sites using a mix of imaging modalities

Lung cancer as a comorbidity of chronic obstructive pulmonary disease

COPD is a risk factor for lung cancer development independent of smoking status, with three to six times more likely to develop lung cancer at a rate of 0.8–1.7%/year. This may be associated with genetic susceptibility to cigarettes, chronic inflammation caused by toxic gases. Inflammatory mediators may promote the growth of bronchioalveolar stem cells, and activation of nuclear factor-κB and signal transducer and activator of transcription 3 play crucial roles in the development of lung cancer from COPD. The aim of the study is to evaluate the prevalence of lung cancer in patients with COPD. We performed a retrospective study, from 2012 to 2022, among patients with pathologically confirmed diagnosis of lung cancer, aged 40-75 years. Patients with lung cancer that had COPD diagnosed >= 10 years before lung cancer diagnosis, were investigated group. Histological subtypes of lung cancer were determined based on histopathology reports and were categorized as squamous carcinoma, adenocarcinoma, small cell lung cancer (SCLC), large cell lung cancer (LCLC; including large cell neuroendocrine carcinoma), and other histological types according to 2015 WHO classification of lung tumors. At the time of registration, sex, age, BMI, smoking status, treatment history, and symptoms, including the CAT score, were recorded. In addition, at the time of registration, spirometry was performed both before and after inhalation of a bronchodilator, and a blood test and chest CT were also performed. The GOLD criteria was used to diagnose and assign severity of COPD: patients with a postbronchodilator FEV1/FVC <0.70 were classified as having COPD; FEV1 ≥0.8 was defined as mild, 0.5≤ FEV1 <0.8 as moderate, 0.3≤ FEV1 <0.5 as severe, and FEV1 ≤0.3 as extremely severe. Patients were excluded if they presented with simultaneous or sequential second primary cancers or had a history of asthma, bronchiectasis, tuberculosis, pulmonary fibrosis, or other confounding diseases. The middle age of lung cancer diagnosis was 61.1±8.5 years. Of the total number of patients with COPD and lung cancer (260), 195 (75.0%) were male and 65 (25.0%) female. 190 (73.07%) were current smokers or ex-smokers. The histological subtypes identified were as follows: squamous carcinoma (96 [36.9%]), adenocarcinoma (115 [44.2%]), SCLC ( 26 [10.0%]), LCLC (13 [5.0%]), and other histologic types (including adenosquamous, carcinoma carcinoid tumors, sarcomatoid carcinoma; 16 [6.15%]). The proportion of squamous carcinoma was higher in smokers/ex smokers with COPD, while adenocarcinoma was more frequently observed in COPD non-smokers. Emphysema predominant phenotype was an independent prognostic risk factor for squamous carcinoma. The prevalence of COPD in lung cancer patients was 35.5%. Compared with lung cancer patients with non-COPD, those with COPD were older (P<0.001), had a lower BMI (P<0.001), and majority were male (P<0.001) and smokers (P<0.001). Annual low-dose computed tomography (LDCT) is an effective procedure for the early detection of lung cancer in high-risk patients like patients with COPD