Diagnostic Challenges in Hemophagocytic Lymphohistiocytosis, a Rare, Potentially Fatal Disease: Two Case Studies.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, and potentially fatal, syndrome, characterized by immune system dysregulation, with excessive activation of the macrophages and cytotoxic T cells. It can be classified into primary (genetic) and secondary (acquired) forms. HLH presents with fever, hepatosplenomegaly, cytopenia, and hyperferritinemia, with involvement of various organs. The initial symptoms of HLH are non-specific, but as, if untreated, it can progress rapidly to multiorgan failure, timely diagnosis is essential. We present here two cases of HLH in infants that illustrate the importance of early diagnosis and appropriate treatment, along with a short review of HLH.

Predictors of negative outcomes in hospitalized patients with SARS­CoV­2 pneumonia: A retrospective study.

The coronavirus disease 2019 (COVID-19) pandemic posed a serious threat to human health worldwide after the first case was identified in December 2019. Specific therapeutic options for COVID-19 are lacking; thus, the treatment of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is complex in clinical practice. Despite the development of treatment options and methods to limit the spread of SARS-CoV-2, certain patients experience critical illness and numerous deaths have occurred. Notably, treatment of this disease is complex due to the evolution of viral mutations and variants with different rates of infection. Moreover, specific patient characteristics may be associated with rapid disease progression and poor outcomes. Thus, the present study aimed to identify the specific characteristics of patients who developed poor outcomes, including clinical manifestations, blood samples (blood cell count and coagulation tests) at hospital admission and comorbidities. The present study included a total of 1,813 patients hospitalized with pneumonia and SARS-CoV-2 infection, and mortality rates associated with each patient characteristic were calculated. The characteristics associated with the highest risk of mortality were as follows: Age >90 years (OR, 105; 95% CI, 17.70-2,023.00); oxygen saturation at the time of hospital admission <89% in room air (OR, 14.3; 95% CI, 7.54-30.7), admission to the Intensive Care Unit (OR, 39.4; 95% CI, 27.7-57.0); and a neutrophil/lymphocyte ratio of 8.76-54.2 (OR, 14; 95% CI, 7.62-29.0). Treatment of patients with SARS-CoV-2 pneumonia represents a challenge for the healthcare system, but there are a number of predictors for poor patient outcomes that could be identified at the time of hospital admission.

Clinical Experience with Anti-IgE Monoclonal Antibody (Omalizumab) in Pediatric Severe Allergic Asthma-A Romanian Perspective.

BACKGROUND: Asthma is the most common chronic disease affecting children, with a negative impact on their quality of life. Asthma is often associated with comorbid allergic diseases, and its severity may be modulated by immunoglobulin E (IgE)-mediated allergen sensitization. Omalizumab is a humanized monoclonal anti-IgE antibody, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omalizumab in Romanian children with severe allergic asthma. METHODS: In this observational real-life study, 12 children and adolescents aged 6 to 18 years (mean 12.4 years) with severe allergic asthma received Omalizumab as an add-on treatment. Asthma control, exacerbations, lung function, and adverse events were evaluated at baseline and after the first year of treatment. RESULTS: We observed general improvement in total asthma symptom scores and reduction in the rate of exacerbation of severe asthma. Omalizumab treatment was associated with improvement in the measures of lung function, and no serious adverse reactions were reported. FEV1 improved significantly after one year of treatment with Omalizumab [ΔFEV1 (% pred.) = 18.3], and [similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rate of asthma decreased from 4.1 ± 2.8 to 1.15 ± 0.78 (p < 0.0001) during the year of treatment with Omalizumab. CONCLUSIONS: This study showed that Omalizumab can be an effective and safe therapeutic option for Romanian children and adolescents with severe allergic asthma, providing clinically relevant information on asthma control and exacerbation rate in children and adolescents. The results demonstrated the positive effect of Omalizumab in young patients with asthma, starting from the first year of treatment.

Respiratory bronchiolitis-associated interstitial lung disease - an unexpected form of idiopathic interstitial pneumonia in a young male.

Cigarette smoking is the most frequently encountered risk factor for chronic obstructive pulmonary disease and lung cancer. The latest American Thoracic Society÷European Respiratory Society classification of idiopathic interstitial pneumonia includes two entities related to smoking habits: respiratory bronchiolitis-associated interstitial lung disease and desquamative interstitial pneumonia. The new approach to diagnosis is to combine pathological pattern with clinical and radiological data. Lung biopsy is no longer considered the "gold standard" for diagnosis, but as a part of the diagnosis, which shall be set only after the pulmonologist, radiologist and pathologist reviewed all clinical, imaging and pathological aspects. We report a case of a young male, who complained of respiratory symptoms, had normal volumes and flows on lung function tests, moderately reduced transfer factor for carbon monoxide and "ground glass" attenuation on high-resolution computed tomography. Because the patient had exposure to contact with parrots, hypersensitivity pneumonitis was considered, but the broncho-alveolar lavage was without lymphocytosis. Open lung biopsy confirmed the diagnosis of respiratory bronchiolitis-associated interstitial lung disease, a rarely described entity in the medical literature. The patient had a good clinical outcome after smoking cessation.

Treatment options in stage III non-small cell lung cancer.

Lung cancer is responsible for over 1 million deaths annually, worldwide. The disease becomes symptomatic in advanced stages, so the diagnosis is delayed and 90% of cases cannot benefit from a curative treatment. In NSCLC surgical resection represents the best option for long term survival in resectable stage III and in clinical stage I/II. Patients with stage IIIB or IV usually receive chemotherapy or palliative treatment. For patients with no driver mutation detected platinum based combination chemotherapy is the first choice. Definitive radiotherapy is considered an lternative for patients who are not candidates for combined modality treatment. When a stage IV cancer is diagnosed based on an isolated metastasis, the patient's benefit from the removal of the etastasis and of the primary tumor if it is resectable. The prognosis in NSLC is mainly influenced by the TNM stage at diagnosis. The rate of survival decreases in opposing correlation with the stage of the cancer. Poor performance status, reduced lung capacity, weight loss, vascular invasion are indicators for a poor prognosis

Infectious cause of an interstitial lung disease.

We present a case of a previously health middleage male patient, without personal history of other condition, who was admitted in our hospital presenting fever, weight loss, and signs and symptoms of acute respiratory distress. The chest computed tomography showed numerous cystic lesions, diffuse ground-glass opacities, honeycombing, and consolidation areas. An HIV infection was confirmed, and the diagnosis of Pneumocystis jirovecii pneumonia was made on induced sputum smear stain. After the initiation of oral treatment with trimethoprim-sulfamethoxazole, the clinical course was rapidly improved. It is important to consider that opportunistic infections such as Pneumocystis jirovecii pneumonia can occur not only in patients previously diagnosed with HIV-infection, but also in patients without a medical history of immunosuppressing disorders.

A rare case of concomitant tuberculosis of the nose, paranasal sinuses and larynx: clinical, histological and immunohistochemical aspects. A case report.

Extrapulmonary tuberculosis is a rare condition determined by Mycobacterium tuberculosis. It can affect any organ, and has a higher incidence with the increase of HIV infection, or in countries with high pulmonary tuberculosis. Diagnosis is difficult, mostly because of non-specific symptoms and a low rate of presentation for medical consult when symptoms do occur. Complete diagnosis is usually set by histological, immunohistochemical examinations, and also with Polymerase Chain Reaction (PCR) in selected cases. The authors present a case of concomitant tuberculosis of the nose, paranasal sinuses and subglottic larynx, without primary involvement of the lungs. The diagnosis was imposed by histological examination and immunostaining of probes obtained in surgery. The treatment was surgical debridement followed by specific antituberculosis medication.

[Uptodate in the management and treatment of ANCA-associated vasculitis]. / Noutati în managementul si tratamentul vasculitelor asociate cu ANCA.

The antineutrophil cytoplasm antibody (ANCA)-associated vasculitis are heterogeneous, multisystem, autoimmune diseases characterized by necrotizing small and medium vessel vasculitis and the association with ANCA. The diagnosis and management of these patients may be challenging due to the variability of clinical features, the possibility of life-threatening events (acute renal failure or pulmonary hemorrhage) and the relative rarity of these syndromes. ANCA-associated vasculitis include granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. The treatment requires significant immunosuppression and there are frequent treatment related side effects. Although the standard protocol with cytotoxic agents and glucocorticoids has dramatically improved patient outcome, its toxic profile remains a major problem. Recent progress in evidence base and consensus in understanding the pathogenic mechanism and the quantification of disease activity further improved patient's life. Special attention was paid in refining immunosuppressive treatment to minimize his toxicity. This review will focus on evidence based treatment of ANCA-associated vasculitis.

[Metabolic profile in obese patients with obstructive sleep apnea. A comparison between patients with insulin resistance and with insulin sensitivity]. / Profilul metabolic al pacientilor cu sindrom de apnee obstructiva în somn si obezitate. Comparatie între pacienti cu insulinorezistenta si pacienti cu insulinosensibilitate.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) may induce metabolic abnormalities through intermittent hypoxemia and simpathetic activation. It is difficult to demonstrate an independent role of OSAS in the occurrence of metabolic abnormalities, as obesity represents an important risk factor for both OSAS and metabolic abnormalities. AIM: to assess the relations between insulin resistance (IR), insulin sensitivity (IS), OSAS severity and nocturnal oxyhaemoglobin levels in obese, nondiabetic patients with daytime sleepiness. MATERIAL AND METHODS: We evaluated 99 consecutive, obese, nondiabetic patients (fasting glycemia < 126 mg/dL, no hypoglycemic or hypolipemiant medication) diagnosed with OSAS (AHI > 5/hour and daytime sleepiness) by an ambulatory six channel cardio-respiratory polygraphy. Hight, weight serum triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) levels were evaluated. Correlations between Apneea Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), average and lowest oxyhaemoglobin saturation (SaO), body mass index (BMI) and insulin resistance or sensitivity were assesed. IR was defined as a TG/ HDL-Cratio > 3, and insulin sensitivity (IS) as a TG/HDL-C ratio < 2. RESULTS: 64 patients (out of 99) had lR and 18 IS. In the IR group (44 men and 20 women), the mean age was 52 +/- 10.6 years, mean BMI: 38.54 +/- 6.67 Kg/m2 (30-60), TG/HDL-C:5, 27 +/- 2.03 (3.02-11.1), mean AHI: 49.65 +/- 25.55/hour (7-110), mean ODI: 4769 +/- 24.95/hour (4-98), mean average SaO2 89.42 +/- 4.6 and mean lowest SaO2 68.4% +/- 13.8% (32-88%). 48 patients had severe, 7 moderate and 9 mild OSAS. In the IS group (10 men and 8 women), the mean age was 58.4 +/- 8.2years, mean BMI: 35.4 +/- 4.29 Kg/m2 (30-46), TG/ HDL-C: 1.64 +/- 0.29 (1.13-1.95), mean AHI: 45.8 +/- 30.3/hour (9-131), mean ODI: 39.9 +/- 32.2/hour (2-133), mean average SaO2 90.8 +/- 8.2 (81-95) and mean lowest SaO2: 74% +/- 10.8% (52-87%). 12 patients had severe, 3 moderate and 3 mild OSAS. Insulin sensitivity positively correlated with mean average SaO2 (r: 0.49; p: 0.037) and negatively with ODI (r: - 0,56; p: 0.014). Insulin resistance negatively correlated with mean lowest SaO2 (r: -0,25; p: 0.045). Mean lowest SaO2 values were significant lower in patients with IR than in those with IS (p: 0.042). No statistically significant difference was found for BMI, AHI or ODI between IR and IS patients. CONCLUSIONS: nocturnal oxyhaemoglobin levels rather than OSAS severity (expressed as AHI or ODI) may be involved in the occurrence of metabolic abnormalities in obese nondiabetic patients. Preserving insulin sensitivity is more likely when oxyhaemoglobin levels are higher and ODI is lower. Mean lowest nocturnal SaO2 levels seems to be independently involved in the development of insulin resistance as no statistically significant differences were found for BMI between the two groups.

New Echocardiographic Tehniques in Pulmonary Arterial Hypertension vs. Right Heart Catheterization - A Pilot Study.

BACKGROUND: Pulmonary arterial hypertension (PAH) represents an emerging pathology in modern medicine. Transthoracic echocardiography is an inexpensive and reproducible method and it is the most commonly used non-invasive diagnostic tool to asses pulmonary artery pressure (PAP) and the function of the right ventricle. Although, the right heart catheterization is still considered as the standard for the diagnosis, according to the last guidelines, the new echocardiographic methods may offer an improved value in the PAH evaluation. AIM: To evaluate if cardiac ultrasonography data correlate with catheterization results in patients with PAH (Group I Dana Point 2008), and to compare the ultrasonography evaluation of PAH patients with that of normal. METHODS: 15 consecutive patients (pts) (52±15 yrs, 5 men, time from onset of symptoms 1.6±1.7 years) with PAH of different aetiologies (12 pts with idiopathic PAH, 2 pts with PAH associated with scleroderma and one with persistent PAH after atrial septal defect (ASD) closure) were evaluated through: 1. clinical examination (NYHA class); 2. exercise capacity (6 minute walking test - 6MWT); 3. conventional echocardiography (diameter of right ventricle - RVD and right atrium, fractional area shortening - FAS, TAPSE, pulmonary ascension time - PA, systolic and mean PAP -sPAP, mPAP, tricuspid E/A ratio, cardiac index-CI) and 4. Tissue Doppler Imaging - TDI (systolic and diastolic myocardial velocities at the tricuspid annulus - S, D, A); 5. right heart catheterization (sPAP, mPAP, CI, pulmonary vascular resistance - PVR)We compared classical and TDI echo parameters with those obtained from 15 normal subjects, matched in age and sex. RESULTS: PAH patients had high sPAP and mPAP with right heart dilation (RV - 44.8±7.3 mm), depressed TAPSE (16.2±5.9 mm) and cardiac index and low TDI systolic velocities at tricuspid level (7.3±2.9 cm/s). All parameters differed statistically significant from normal. There were no significant correlations between ultrasonography and catheterization (cath) parameters (sPAP 92±28.2 echo vs. 106.4±25.8 mmHg cath; mPAP 47.9±8.4 echo vs. 65.8±17.3 mmHg cath), excepting for CI 2.3±1.2 l/min/m(2) vs. 2.08±0.3 ml/min/m(2)) and PVR (16.5 ± 15.3 Wood U echo, vs. 19.6 ± 7.9 cath). CONCLUSION: Classic and TDI cardiac ultrasonography represents a good screening and monitoring tool for PAH patients, but tends to underestimate the severity of the disease, leaving right heart catheterization as the essential diagnostic method for this rare disease.

The role of overnight pulse-oximetry in recognition of obstructive sleep apnea syndrome in morbidly obese and non obese patients.

MATERIAL AND METHODS: We prospectively evaluated 199 individuals with high pre-test clinical suspicion of OSAS. Of these, 123 patients were morbidly obese (Group A) and 76 were non-obese (Group B). We performed six channel cardio-respiratory polygraphy and assessed the correlation between the Desaturation Index (DI) and the Apnea Hypopnea Index (AHI) for both groups. RESULTS: In group A: 116 patients (94.3%) were diagnosed with OSAS (AHI>5/hour); mean age: 59.4±10.9 years; mean BMI: 44.8±4.9 kg/m(2). The mean DI was 47.2±27.6/hour and the mean AHI: 46.5±27.6/hour. Mean average SaO2 was 88.5±6.3 %. In group B, 65 patients (85.52%) were diagnosed with SAS; mean age: 51.2 ± 12.7 years; mean BMI: 27.24±2.2 kg/m(2).The mean DI was 23.12 ± 18.35/hour and the mean AHI: 28.8 ± 18.5/hour. Mean average SaO2 was 93.7±2.07 %.A significant positive correlation (correlation index rA = 0.863 and rB= 0.877) was found between DI and AHI in both groups (p<0.001). CONCLUSION: Assessment of the Desaturation Index by nocturnal pulse-oximetry maintains its utility as a screening method for OSAS in both obese and non-obese patients with high clinical pre-test suspicion, despite the fact that the basal nocturnal saturation was found to be lower in group A.

Unilateral pulmonary hilar tumor mass: is it always lung cancer?

Sarcoidosis is a multisystem inflammatory disease of unknown etiology, characterized by noncaseating epithelioid cell granulomas. In sarcoidosis, the most common radiological findings are mediastinal and bilateral hilar lymph node enlargement. We present a case of sarcoidosis with a rare radiological aspect of pulmonary hilar tumor mass.A 54-year-old female patient, active smoker (40 packs/year), with a history of cutaneous lupus, was admitted in our institute for progressive dyspnea and dry cough. At admission physical examination and laboratory tests were normal. Pulmonary function tests diagnosed an obstructive syndrome. Chest X-ray showed a tumor mass of the right pulmonary hilum. Transbronchial biopsy was nondiagnostic. HRCT-scan showed a tumor mass in the right hilum, which raised the suspicion of a lung cancer. PET-CT scan revealed a high metabolic activity of the tumor mass and of a paratracheal right lymphadenopathy. Lymph node biopsy by mediastinoscopy showed noncaseating epithelioid-cell granulomas, sustaining the diagnosis of sarcoidosis. The outcome was favorable, with spontaneous remission without treatment, but with a relapse that responded after systemic corticotherapy.In conclusion, even if a tumor mass in the pulmonary hilum is highly suggestive of lung cancer, a positive diagnosis should be made only after histological examination, because other benign conditions, like sarcoidosis, could have such an aspect.

A rare case of lung tumor -- pulmonary inflammatory pseudotumor.

Pulmonary inflammatory pseudotumor (PIP) is a rare condition of unknown etiology. It is still a matter of debate if it represents an inflammatory lesion characterized by uncontrolled cell growth or a true neoplasm. Although mostly benign, these tumors are diagnosis and therapeutic challenges. Preoperative diagnosis can rarely be established. The treatment of choice is surgical resection which has both diagnostic and therapeutic value. We report the case of a 63-year-old male presented with clinical and imagistic picture suggestive of malignancy in the thorax. Lobectomy was performed with histological diagnosis of PIP. No evidence of tumor recurrence.

[Radiation induced lung injuries secondary to radiotherapy for breast cancer]. / Tipuri de leziuni pulmonare secundare radioterapiei pentru cancer mamar.

UNLABELLED: Modern radiotherapy decreased the number and severity of the effects of irradiation on the lung. Yet, the increased cancer incidence makes the related radiation injuries to remain actual, radiotherapy being frequently used in cancer treatment. Aim of the study consists in analysis of the radiological pattern of radiation induced lung disease due to radiotherapy for breast cancer. MATERIAL AND METHOD: Sixty-eight female patients were evaluated for clinical and radiological suspicion of radiation pneumonitis after radiotherapy for breast cancer between 2001 and 2009 in "Marius Nasta" Institute of Pneumophtiziology, Bucharest. The following procedures were performed: medical history, physical examination, chest radiography and CT-scan (in a subgroup of 27 patients). Radiotherapy toxicity was evaluated based on the RTOG/EORTC (Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer) classification and radiological lesions based on Arriagada classification. RESULTS: Fifty patients (73.5%) were symptomatic (fever, dry cough, dyspnea, chest pain, fatigability), the other 18 were asymptomatic. Symptoms were mild to moderate corresponding to grade 1 (27 patients, 39.7%) or grade 2 (23 patients, 33.8%) according to RTOG/EORTC scale. All patients had radiological lesions: 25 patients (36.7%) had grade 2 lesions (linear opacities), 25 patients (36.7%) had grade 3 lesions (patchy opacities) and 18 patients (26.5%) had grade 4 lesions (dense opacities), according to Arriagada classification. Symptoms were more frequent in patients with extensive lesions on chest radiography. CT-scan, performed in 27 patients, showed more accurate images. CONCLUSIONS: Chest radiography remains the simplest method in screening for radiation pneumonitis and monitoring its outcome. Adverse effects secondary to radiotherapy are usually mild and self-limited, and the most difficult task remains the differential diagnosis with infections and cancer relapse.

The bronchoalveolar lavage pattern in radiation pneumonitis secondary to radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: Radiotherapy in breast cancer patients is limited by lung tissue tolerance. Two complications involving the lung are known: radiation pneumonitis (RP) and radiation fibrosis. The aim of the study was to evaluate the pattern of bronchoalveolar lavage (BAL) in patients with RP after radiotherapy for breast cancer in symptomatic and asymptomatic patients. MATERIAL AND METHODS: Sixty-five female patients (mean age 58.3 yrs) with RP after radiotherapy for breast cancer were included in the study. The majority of patients had previous breast surgery (mastectomy or lumpectomy and axillary dissection) and received doses of radiations of 45-50Gy. All patients had adjuvant chemotherapy with cyclophosphamide, 5-fluorouracil, and epirubicin or methotrexate. RESULTS: All patients had an infiltrate or consolidation on chest radiography confined to the upper lobe of the irradiated lung, as marker of RP. Based on the presence or absence of symptoms, we divided the patients in 2 groups: 49 patients (75.4%) with symptomatic RP (fever, cough, dyspnea, chest pain and fatigue) and 16 patients (24.6%) without any symptom. Symptomatic RP patients had a BAL with significant increase in total cells (18.0±12.2 x10(6) cells•100mL-1) when compared to BAL in asymptomatic patients (11.9±6.2 x10(6) cells•100mL-1), p=0.01. Lymphocytosis in BAL was significantly increased in symptomatic group, compared with asymptomatic one (35.4±18.7% vs. 26.1±14.3%, p=0.045), with predominance of T lymphocytes (CD3). It was also a predominance of CD4 lymphocytes in all patients, but the CD4/CD8 ratio was inside normal range in the majority of cases. Five patients had clinical features of bronchiolitis obliterans organizing pneumonia (BOOP) secondary to irradiation with increased percentages of lymphocytes, neutrophils, eosinophils, and mast cells in BAL and one patient without history of atopic disease had a percentage of 40% eosinophils. Only a mild reduction in diffusing capacity for carbon monoxide was seen in both groups on pulmonary function tests. The lung volumes were normal in all patients. CONCLUSIONS: Lymphocytic alveolitis was the marker of radiation pneumonitis in all patients. The degree of the inflammatory reaction of the lungs was correlated with the presence of symptoms. The lymphocytic alveolitis consisted mainly of T lymphocytes, with a predominance of CD4 subset in both groups, but the CD4/CD8 ratio remained mostly into normal range.