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.

The Challenging Diagnosis of Interstitial Lung Disease in Children-One Case Report and Literature Review.

Childhood interstitial lung disease (chILD) includes a heterogeneous spectrum of rare respiratory disorders in children associated with substantial morbi-mortality. Interstitial tissue, and other pulmonary structures, epithelium, blood vessels, or pleura are involved, resulting in a restrictive lung disfunction. Respiratory symptoms set in progressively and are often subtle, making thorough clinical history and physical examination fundamental. The etiology often is obscure. The clinical presentation mimics pneumonia or asthma, leading to a diagnostic delay. Challenging diagnosis may require genetic tests, bronchoalveolar lavage, or lung biopsy. Alongside general supportive therapeutic measures, anti-inflammatory, immunosuppressive or antifibrotic agents may be used, based on data derived from adult studies. However, if accurate diagnosis and treatment are delayed, irreversible chronic respiratory failure may ensue, impacting prognosis. The most frequent chILD is hypersensitivity pneumonitis (HP), although it is rare in children. HP is associated with exposure to an environmental antigen, resulting in inflammation of the airways. Detailed antigen exposure history and identification of the inciting trigger are the cornerstones of diagnostic. This article provides the current state of chILD, revealing specific features of HP, based on a clinical case report of a patient admitted in our clinic, requiring extensive investigations for diagnosis, with a favorable long-term outcome.

Combined Effects of Vitamin D Status, Renal Function and Age on Serum Parathyroid Hormone Levels.

Background: Vitamin D status and renal function are well-known independent predictors of serum parathyroid hormone (PTH) levels. We aimed to describe the combined effects of 25-hydroxy vitamin D (25(OH)D), glomerular filtration rate (GFR) and age on serum PTH levels across the whole clinical spectrum. Methods: We retrieved from our endocrinology center database all PTH measurement between 2012 and 2020 for which a simultaneous measurement of serum 25(OH)D, calcium and creatinine was available. Age, sex and diagnosis were available for all subjects. Intact PTH was measured using the same electrochemiluminescence assay. Results: There were 6,444 adults and 701 children without a diagnosis of hyper- or hypoparathyroidism or abnormal serum calcium levels. In adults with 25(OH)D≥12 ng/mL multiple regression models showed that serum PTH was negatively correlated with both 25(OH)D and GFR. Regression (-0.68 and -1.59 vs. -0.45 and -0.22 respectively), partial correlation (-0.16 and -0.35 vs. -0.12 and -0.10 respectively) and determination coefficients (0.14 vs. 0.031) were higher in CKD than in normal renal function. In subjects with 25(OH)D<12 ng/mL, GFR was the only significant predictor in those with CKD (ß-coefficient=-2.5, r=-0.55) and 25(OH)D was the only significant predictor in those with normal renal function (ß-coefficient=-2.05, r=-0.11). Increasing age was associated with higher PTH levels only in those with normal renal function and 25(OH)D≥12 ng/mL. Conclusions: We showed that declining vitamin D and renal function have additive effects on serum PTH in subjects without vitamin D deficiency. In vitamin D deficient subjects this dependency is stronger but is not additive anymore.

Respiratory Failure in a Rare Case of Juvenile Dermatomyositis - Systemic Scleroderma Overlap Syndrome.

Juvenile dermatomyositis (JDM) is one of the pediatric systemic connective tissue disorders, consisting of an idiopathic inflammatory myopathy, affecting primarily skin and muscle, representing approximately 85% of cases in this group. A significant source of morbidity is the occurrence of overlap characteristics with other connective tissue disorders, including systemic sclerosis (SSc). Overlap JDM/SSc syndrome is rare in children, with only a few reported cases. The diagnosis is often challenging, presence of anti-PM/Scl antibodies playing a pivotal role. Although SSc/JDM overlap syndrome has less frequent visceral involvement, pulmonary dysfunction may occur. The respiratory function evaluation using overnight cardiorespiratory polygraphy may reveal important alveolar hypoventilation with impact on therapeutic approach. Non-invasive ventilation may be indicated to potentiate medical treatment. In the acute phase, non-invasive ventilation is a life-saving therapeutic option until the maximum efficiency of drug treatment is reached. In the case of a complex respiratory pathology, associating elements of nocturnal alveolar hypoventilation specific to neuromuscular disease, with that of chronic interstitial lung disease, the evaluation of respiratory sleep disorders should be considered, sometimes requiring home nocturnal noninvasive ventilatory support. We present the case of a 15-year-old girl who was admitted to our clinic with a history of high fever, productive cough and severe dyspnea. Detailed anamnesis revealed that the patient accused oneyear history of proximal muscle weakness of the lower limbs, with functional limitations, weight loss, dysphonia, swallowing difficulties and dyspnea at minimal efforts. Following the physical examination, laboratory and imagistic investigations were all suggestive for an inflammatory myopathy. Anti-PM/Scl antibodies were positive, confirming the diagnosis of a severe form of JDM/SSc overlap syndrome, with minimal cutaneous changes, significant muscle involvement and respiratory distress. Complex therapy using antimicrobial agents, steroid pulse therapy, immunosuppressive agents, non-invasive ventilation, masticaoxygen supplementation and physiotherapy was started, with significant status improvement. However, pulmonary function tests maintained severe restrictive aspect and nocturnal cardio-pulmonary polygraphy revealed residual pulmonary failure with important nocturnal alveolar hypoventilation. Nocturnal non-invasive ventilation was continued at home, along with medical treatment. Her disease was clinically well controlled, immunosuppressive therapy was decreased and interruption of ventilatory support was possible at six months after the diagnosis.

Conjunctival Benign Fibrous Histiocytoma in a 57-year-old man.

Purpose. To report a case of benign fibrous histiocytoma of the conjunctiva involving the cornea, an uncommon ocular surface tumor. Methods. A 57-year-old patient came in our service complaining of a progressively enlarging conjunctival mass temporally to the limbus and invading the adjacent cornea of the left eye. Results. The approach consisted in surgical excision followed by cryotherapy on the edges and on the base of the excision site and amniotic membrane patch reconstruction of the ocular surface defect. Pathologic examination and immunohistochemistry were performed in order to establish the diagnosis. No recurrences appeared in 8 months of follow up. Conclusions. Fibrous histiocytoma might be easily misdiagnosed as it is exceedingly rare. Complete resection with careful inspection of edges is advised. Cryotherapy at the base and borders of the resection site is recommended as both benign and malignant tumors can show recurrence. Amniotic membrane should always be regarded as an efficient option in reconstruction of broad surface defects after tumor resection. Abbreviations: FH = fibrous histiocytoma, CIN = corneal intraepithelial neoplasia, SSCA = squamous cell carcinoma, AM = amniotic membrane, MMC = topical mitomycin-C, 5-FU = 5-fluorouracil, BCVA = best corrected visual acuity.

Disposition Index in Active Acromegaly.

Background: The relative contribution of reduced insulin sensitivity (Si) or insulin secretion to impaired fasting glucose (IFG) or diabetes mellitus (DM) has not been clarified in active acromegaly. An intravenous glucose tolerance test (IVGTT) was never used for the calculation of Si, acute insulin response (AIRg), and disposition index (DI) in this population. Our aim was to assess Si, AIRg and DI using an IVGTT in acromegaly with normal (NGT) and abnormal glucose tolerance. Methods: We performed an IVGTT in 13 patients (8 NGT, 2 IFG, and 3 DM; 5 males, age 47.9 ± 11 years, body mass index 29.7 ± 4.1 kg/m2) with active acromegaly (insulin-like growth factor-1 4.1 ± 1.3 × upper limit of normal, basal GH 29.1 ± 25 ng/mL) and 3 healthy controls (2 males, age 39 ± 3 years, body mass index 23 ± 5 kg/m2). No patient had any growth hormone- or glucose-lowering medication. Results: NGT patients had significantly lower Si than healthy controls but higher AIRg. Hyperglycemic and normoglycemic patients had similar Si. DM patients had severely diminished AIRg (5-260 pmol × min/L) while IFG patients maintained their insulin secretion (3,862 and 912 pmol × min/L). Patients with abnormal glucose tolerance (IFG + DM) had a significantly lower DI (353 ± 350) than both NGT patients (3,685 ± 2,544) and healthy controls (5,837 ± 1,894; p < 0.01 for ANOVA). Conclusions: Disposition index suggests that although reduced insulin sensitivity is characteristic of active acromegaly it is the impaired insulin secretion that mainly drives glucose intolerance. The clinical utility of DI in predicting DM in acromegaly must be further investigated.

Evolutionary Particularities in a Case of Severe Pneumonia in Children - Case Report.

Necrotizing pneumonia remains an uncommon complication of pneumonia in children, but its incidence is increasing. Pneumococcal infection is the predominant cause of severe necrotizing pneumonia in children, but methicillin resistant Staphylococcus aureus (MRSA) and Panton-Valentine leukocidin (PVL) staphylococcal infections are also important. We present the case of a four-year-old girl,with an unremarkable medical history, who was admitted in our hospital with a history of high fever, productive cough and tachypnea lasting for 10 days, progressive worsening despite empirical oral antibiotic. Following physical examination, laboratory investigations and thoracic radiography, we established the diagnosis of left lower lobe pneumonia with parapneumonic effusion, acute respiratory failure and sepsis. Medical treatment with systemic antibiotics was initiated, but the evolution was unfavorable. Seriated chest X-rays and also high resolution computed tomography with contrast of the lung were performed, revealing the progression to extensive necrotizing pneumonia with multiple cystic lesions causing right mediastinal deflection. The parenteral broad spectrum antibiotic regimen was adjusted, still with unfavorable evolution, requiring surgical treatment (left inferior lobectomy and pleural draining). Postoperatively, recovery was uneventful. The patient was discharged with clinical and laboratory improvement of his condition, a repeated chest X-ray showing good expansion of upper left parenchyma.

Central Sleep Apnea - a Rare Cause for Acute Respiratory Insufficiency in Children. Case Report.

Central sleep apnea is characterized by frequent cessation of breathing during sleep, resulting in repetitive episodes of insufficient ventilation and abnormalities of acid-base balance. It may be primary or secondary, and it is uncommon in children, with limited data for this population. We present here the case of a five-year-old girl, known to have thoracolumbar myelomeningocele (for which she underwent a surgical procedure in infancy), secondary hydrocephalus (with a ventriculoperitoneal shunt) and flaccid paralysis, who was admitted in our hospital with prolonged fever syndrome, productive cough, severe dyspnea and perioral cyanosis. Following physical examination, laboratory investigations and thoracic radiography, we established the diagnosis of aspiration pneumonia with acute respiratory failure. Medical treatment with multiple systemic antibiotics, antifungal agents, systemic and inhaled bronchodilator, oxygen therapy and respiratory nursing were initiated, with favorable evolution. During the entire hospitalization, the patient showed nocturnal respiratory rhythm disorders, with sleep apnea crisis of approximately 20 seconds and desaturation, followed by severe hypercapnic respiratory acidosis, manifestations that persisted even after the remission of pulmonary infection, raising the suspicion of an apnea syndrome. After excluding the causes of obstructive apnea, a cerebral CT scan was performed, revealing isolated fourth ventricle compressing the brainstem. The patient underwent neurosurgical intervention and postoperatively, the evolution was favorable, with remission of apnea crisis.

The process of liver fibrosis in chronic hepatitis C - histological and immunohistochemical study.

Liver fibrosis is one of the most serious histopathological (HP) lesions that, together with the inflammatory process and the hepatocyte lesions, determine the change of the liver architecture, having as a clinical result the onset of liver failure phenomena. Hepatitis C virus represents one of the most frequent conditions leading to the onset of liver fibrosis and favors the progression of the disease towards hepatocellular carcinoma. We evaluated the HP and immunohistochemical (IHC) aspects on fragments of liver biopsies taken from 104 patients diagnosed with chronic hepatitis C and altered capacity of work. In our study, we observed a growth of the portal (Kiernan) spaces by the presence of a chronic inflammatory infiltrate, the presence of collagen fibers and conjunctive matrix. The density and dimensions of collagen fibers were correlated with the severity of the liver disease, in the severe forms being highlighted porto-portal and porto-central fibrous bridges. The IHC examinations highlighted the change of the phenotype of perisinusoidal dendritic cells, the growth of the myofibroblast cells in the portal spaces, the growth of the macrophage number in the inflammatory infiltrate and of the Kupffer cells in the liver parenchyma.

Anatomo-clinical correlations in hepatic steatosis in patients with C chronic hepatitis.

Hepatic steatosis is a progressive liver disease, frequently met in chronic virus C hepatitis, playing an important role in its evolution towards fibrosis, necroinflammation and the final stage the hepatocellular carcinoma. The present paper studies the correlation between clinico-epidemiological parameters and the pathology test outcome in patients with hepatic biopsies carried out before they began the antiviral treatment. We used the classical histological staining and the immunolabeling. The presence of steatosis is not directly associated with clinico-epidemiological parameters and with the degree of fibrosis and inflammation.

Antifibrotic action of telmisartan in experimental carbon tetrachloride-induced liver fibrosis in Wistar rats.

BACKGROUND AND AIMS: Liver fibrosis is the increasingly accumulation of extracellular matrix (ECM), caused by chronic liver injuries, and represents a difficult clinical challenge in the entire world. Currently, the advanced knowledge of the cellular and molecular mechanisms of liver fibrosis showed that collagen-producing cells, like activated hepatic stellate cells (HSCs), portal fibroblasts and myofibroblasts are activated by fibrogenic cytokines, such as angiotensin II, transforming growth factor-beta 1 (TGF-ß1), and leptin. Because of these, we tested telmisartan, an angiotensin II (AT1) receptor blocker and a peroxisome proliferator-activated receptor-γ (PPARγ) partial agonist, for investigate its antifibrotic action, on experimental model of carbon tetrachloride-induced liver fibrosis. MATERIALS AND METHODS: In this research, we used two groups of Wistar rats, which received intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) 40% dissolved in olive oil, twice weekly for four consecutive weeks (initial dose of 5 mL÷kg, and other doses 3 mL÷kg). After one week, one group was received by gavage telmisartan (TS) dissolved in saline 0.9%, daily in dose of 8 mg÷kg, for 28 days. One group of Wistar rats was used for control. The antifibrotic action of telmisartan was investigated on the pathological changes of the liver and immunohistochemical analysis for hepatic stellate (Ito) cells (HSCs) reaction using anti-alpha-smooth muscle actin (anti α-SMA) antibody and macrophages cells (Kupffer cells) reaction using anti-CD68 antibody. RESULTS AND CONCLUSIONS: In group treated with telmisartan, hepatic fibrogenesis process was significantly reduced, in comparison with CCl4 group.

[Study of Streptococcus pneumoniae strains resistant to antibiotics analyzed at "Cantacuzino" NIRDMI during 2006-2008]. / Studiul tulpinilor de Streptococcus pneumoniae rezistente la antibiotice analizate la INCDMI "Cantacuzino" în perioada 2006-2008.

OBJECTIVE: The aim of the this study was the analysis of the resistance to antibiotics of Streptococcus pneumoniae isolated in last years. METHODS: 328 S. pneumoniae strains, coming from blood, CSF tracheal aspirate (TA), or sputum, pleural fluid (PL) and other samples (ear and sinus fluid) isolated in 2006-2008, were analyzed at INCDMI "Cantacuzino", National Reference Center for Streptococcus pneumoniae. Strains were tested for susceptibility to by agar diution method (minimal inhibitory concentration-MIC) to the following antibiotics: penicillin (Pc), erythromycin (Em), cephalothin (Kf). cefuroxim (Cxm), cefotaxim (Ctx), trimethoprim/sulfamethoxazol (Sxt), ofloxacin (Ojx), amoxicillin (Amx). tetracycline (Te), cloramphenicol (Cm), vancomycin (Va). RESULTS: The analysis of the results was done according to CLSI 2009. Pneumococci strains isolated from blood, CSF, TA or sputum and PL showed lower resistance level to antibiotics (38.8% Pc, 9.3% Cxm. 4.1% Ctx, 2.7% Amx. 24% Em, 2.4% Ofx, 68% Sxt) against those isolated from ear ans sinus fluid which revealed high levels of resistance (70% Pc, 11.2 % Cxm, 5.9 % Ctx, 3.4% Amx, 58.4 % Em. 3.8% Ofx, 73% Sxt). Strains resistant to penicillin, isolated from blood and CSF revealed the following aspects: 17% low level of resistance and 11 % high level of resistance. CONCLUSIONS. The most efficient antibiotics were Ctx, Amx and Oft. A continuous surveillance of pneumococci strains resistant to antibiotics is needed, as well as the use of an pneumococcal efficient vaccine.