Frequent Laboratory Abnormalities Research Articles

Comparison of clinical and MRI features of hepatic angiosarcoma and epithelioid hemangioendothelioma.

Differentiating hepatic epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS), the two most common vascular tumors in the liver, is important due to disparities in their prognosis and treatment. We aimed to compare clinical and MRI features of the two tumors. This retrospective study included patients with pathologically-confirmed AS or EHE who underwent MRI using gadoxetate disodium between 2008 and 2023. Two radiologists independently reviewed MR images. Wilcoxon rank sum and Fisher's exact tests were used to compare clinical and imaging features. Overall survival was compared using restricted mean survival time at 3years. 32 patients with AS (18 women [56.3%]; median age, 68years) and 38 with EHE (24 women [63.2%]; 51years) were included. Patients with AS were generally older (81.3% ≥ 60years; P < 0.001), had more frequent laboratory abnormalities (P ≤ 0.018), and poorer overall survival (11.2 vs. 31.8months; P < 0.001) than those with EHE. On MRI, a large dominant mass accompanied by smaller nodules (14/32, 43.8%), often with ill-defined margins (15/32, 46.9%) was prevalent in AS; compared with nodules of similar sizes (24/38, 63.2%; P = 0.015) with well-defined margin (30/38, 78.9%; P = 0.002) in EHE. Cirrhotic appearance of the liver was more frequent in AS (62.5%, P < 0.001), along with decreased parenchymal enhancement on hepatobiliary phase (31.3%, P < 0.001) and ascites (37.5%, P = 0.010). AS frequently presented with avid enhancement of bizarrely-shaped foci, with a centrifugal enhancement pattern. In comparison, targetoid appearance was characteristic of EHE (78.9% on T2-weighted, 54.1% on diffusion-weighted, 65.8% on multiphase images) (P ≤ 0.002), with enhancement degree typically lower than that of the aorta. On hepatobiliary phase, all the AS exhibited hypointensity, while 39.5% of EHE showed targetoid appearance (P < 0.001). Patients aged ≥ 60years presenting with laboratory abnormalities, typically with a large dominant mass accompanied by smaller nodules, exhibiting avid, bizarre, and centrifugal enhancement-particularly in the cirrhotic-appearing liver-suggests the likelihood of AS over EHE.

Safety and toxicity of cabozantinib monotherapy in patients with advanced renal cell carcinoma: a Russian multicenter observational study

Aim. To assess the safety and to analyze an influence of cabozantinib monotherapy toxicity on treatment efficacy in unselected Russian patients with metastatic renal cell carcinoma (mRCC).&#x0D; Materials and methods. Medical data of 92 patients with verified mRCC were included in the study. The median age of the patients was 56 (1979) years, most of them - 60 (65.2%) were of male gender. Twenty five (27.2%) persons had Eastern Cooperative Oncology Group performance status (ECOG PS). At the time of cabozantinib monotherapy start 5 (5.4%) patients had favorable, 54 (58.7%) intermediate, and 33 (35.9%) unfavorable prognosis by International Metastatic Renal Cancer Database Consortium (IMDC) model. Eighty-three (90.2%) patients were pretreated, including 76 (82.6%) patients who previously received anti-angiogenic agents. All patients were administered with cabozantinib monotherapy (60 mg/day); dose adjustment was performed according to the instruction.&#x0D; Results. Adverse events (AEs) were reported in 81 (88.0%) of 92 patients; 30 (32.6%) AEs were grade 34. Toxicity-related dose reduction of cabozantinib was required in 28 (30.4%), treatment interruption in 15 (16.3%), and discontinuation in 2 (2.2%) patients. The most common AEs were hypertension (69 patients, 75.0%), asthenia (47 patients, 51.1%), diarrhea (43 patients, 46.7%), and palmar-plantar erythrodysesthesia (43 patients, 46.7%). The most common severe AEs were: arterial hypertension (17 patients, 18.5%), diarrhea (6 patients, 6.5%), and palmar-plantar erythrodysesthesia (2 patients, 2.2%). The most frequent laboratory abnormalities during therapy were elevated serum transaminases (33 patients, 35.9%), anemia (13 patients, 14.1%), and thrombocytopenia (10 patients, 10.9%). No previously unreported AEs or laboratory abnormalities were observed. There was a significant increase in progression-free survival (hazard ratio 2.5; 95% confidence interval 1.05.9; p=0.046) and overall survival (hazard ratio 3.0; 95% confidence interval 1.28.3; p0.025) in patients with treatment-related arterial hypertension.&#x0D; Conclusion. The observational study confirmed the acceptable safety profile of cabozantinib in the first and subsequent lines of treatment in mRCC patients. No new safety signals were identified. Treatment-related arterial hypertension may be a favorable predictor of survival.

Frequency of alterations in laboratory analytical parameters in patients with HIV under antiretroviral treatment treated in the Infectious Diseases Unit of Hospital de Especialidades José Carrasco Arteaga during the period 2018 - 2019.

BACKGROUND: According to the WHO, in 2021 there were 28.7 million people infected with HIV in the world under antiretroviral treatment. Although antiretroviral therapy has improved the survival of people with HIV, the adverse effects caused directly or indirectly by antiretroviral therapy have caused poor adherence to it, leading to therapeutic failure. The aim of this study is to determine the frequency of laboratory parameters alterations in HIV patients under treatment with antiretroviral drugs. METHODS: A descriptive, observational and cross-sectional study was carried out. The sample consisted of 233 patients diagnosed with HIV under antiretroviral treatment, treated at the Infectious Diseases Unit of Hospital de Especialidades José Carrasco Arteaga. The analyzed variables were: age, sex, treatment regimen; alterations were sought in the following variables: lymphocyte count, hemoglobin, blood triglycerides, blood glucose, neutrophil count, transaminases, bilirubin, creatinine, urea and lactic acid. RESULTS: The majority of patients were male (86.70%), mainly between 30 and 39 years of age (33.91%). The most used scheme was "Tenofovir + Emtricitabine + Efavirenz" (57.94%). The laboratory analytical alteration presented most frequently in all treatment schemes, except for Tenofovir+ Emtricitabine + Lopinavir+ Ritonavir, was hypertriglyceridemia (25.75%). 24.46% of the patients did not present any analytical alteration. CONCLUSION: The majority of HIV patients during 2018-2019, in HEJCA, were male, between 30 and 39 years of age. The most widely used treatment scheme was "Tenofovir + Emtricitabine + Efavirenz". Hypertriglyceridemia was the most frequent laboratory abnormality, followed by hyperglycemia and anemia. A quarter of the study population did not show any laboratory abnormalities with the prescribed treatment schemes.

Murine Typhus: An Overlooked Enemy

Fever due to murine typhus caused by Rickettsia typhi is underdiagnosed in pediatrics due to nonspecific symptoms. We summarize its clinical presentation in children to increase pediatricians' awareness of murine typhus. The classic triad of fever, headache, and rash is encountered in less than half of patients. Other common symptoms in children include nausea, vomiting, and abdominal pain. Frequent laboratory abnormalities in pediatric patients include elevated liver enzymes, lactate dehydrogenase, and erythrocyte sedimentation rate, as well as anemia. There is seasonal and geographic distribution, with most cases reported during warmer months in the Gulf Coast and California in the United States, often associated with flea or animal exposure for children. Pulmonary, neurologic, and renal complications are possible, although mortality is low. Patients of any age respond quickly to the initiation of doxycycline therapy. [ Pediatr Ann . 2022;51(11):e436–e439.]

EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS WITHOUT ANY PERIPHERAL EOSINOPHILIA

EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS WITHOUT ANY PERIPHERAL EOSINOPHILIA

COVID-19 in Neonates with Positive RT–PCR Test. Systematic Review

BackgroundCOVID-19 is an infectious disease of variable severity caused by a new coronavirus. Clinical presentation ranges from asymptomatic cases to severe illness. Most cases in newborns appear to be asymptomatic or mild.ObjectiveTo conduct a systematic review of the literature on published studies of COVID-19 in newborns with a positive RT–PCR test.MethodsThe PubMed and EMBASE databases were searched for infection data in newborns from 1 December 2019–21 May 2021. The mesh terms included “SARS-CoV-2”, “COVID-19”, “novel coronavirus”, “newborns” and “neonates”. The selection criteria were as follows: original studies reporting clinical, radiological, laboratory, and outcome data in newborns with a positive RT–PCR test for SARS-CoV-2. Two independent investigators reviewed the studies.ResultsSeventy-two studies that involved 236 newborns were included. The main clinical manifestations were fever (43.2%), respiratory (46.6%), and gastrointestinal (35.2%) symptoms; 60.1% had mild/moderate disease. A total of 52.5% had a chest X-ray; 43.5% were normal, and 24.1% reported consolidation/infiltration images. The most frequent laboratory abnormalities were elevated C reactive protein and elevated procalcitonin and lymphopenia. Mortality was 1.7%.ConclusionSymptoms of SARS-CoV-2 infection were mild to moderate in most of the newborns. The prognosis was good, and mortality was mainly associated with other comorbidities.

Clinical spectrum and predictors of severity of dengue among children in 2019 outbreak: a multicenter hospital-based study in Bangladesh

BackgroundThe mosquito-borne arboviral disease dengue has become a global public health concern. However, very few studies have reported atypical clinical features of dengue among children. Because an understanding of various spectrums of presentation of dengue is necessary for timely diagnosis and management, we aimed to document the typical and atypical clinical features along with predictors of severity among children with dengue during the largest outbreak in Bangladesh in 2019.MethodsWe conducted a cross-sectional study between August 15 and September 30, 2019. in eight tertiary level hospitals in Dhaka city. Children (aged < 15 years) with serologically confirmed dengue were conveniently selected for data collection through a structured questionnaire. Descriptive, inferential statistics, and multivariable logistic regression were used to analyze data.ResultsAmong the 190 children (mean age 8.8 years, and male-female ratio 1.22:1) included in the analysis, respectively 71.1 and 28.9% children had non-severe and severe dengue. All children had fever with an average temperature of 103.3 ± 1.2 F (SD). Gastrointestinal symptoms were the most common associated feature, including mostly vomiting (80.4%), decreased appetite (79.5%), constipation (72.7%), and abdominal pain (64.9%). Mouth sore, a less reported feature besides constipation, was present in 28.3% of children. Atypical clinical features were mostly neurological, with confusion (21.3%) being the predominant symptom. Frequent laboratory abnormalities were thrombocytopenia (87.2%), leucopenia (40.4%), and increased hematocrit (13.4%). Age (AOR 0.86, 95%CI 0.75–0.98, p = 0.023), mouth sore (AOR 2.69, 95%CI 1.06–6.96, p = 0.038) and a decreased platelet count (< 50,000/mm3) with increased hematocrit (> 20%) (AOR 4.94, 95%CI 1.48–17.31, p = 0.01) were significant predictors of severity.ConclusionsDengue in children was characterized by a high severity, predominance of gastrointestinal symptoms, and atypical neurological presentations. Younger age, mouth sores, and a decreased platelet with increased hematocrit were significant predictors of severity. Our findings would contribute to the clinical management of dengue in children.

Derazantinib (DZB) in combination with atezolizumab (AZB) in patients with solid tumors: Results from the dose-finding phase Ib substudy of FIDES-02.

437 Background: DZB is an oral small-molecule FGFR1/2/3 kinase inhibitor, which demonstrated antitumor activity in preclinical and clinical studies (in cholangiocarcinoma patients [pts] with FGFR2-driven tumors and in FGFR1-3-driven urothelial cancer [UC] PDX models). In CSF1-stimulated mouse bone-marrow derived macrophages, DZB reduced CSF1R phosphorylation with a maximal effect similar to the selective CSF1R inhibitor BLZ945, suggesting DZB could have an effect on tumor-associated macrophage regulation. Thus, DZB+AZB is a rationale combination to be investigated in immunogenic and FGFR-driven tumors like UC. Methods: FIDES-02 is a multi-cohort open-label Phase 1b/2 study evaluating the effect of DZB as monotherapy and DZB+AZB in combination. To determine the RP2D of DZB+AZB, a total of 26 pts with UC (N = 4) and other solid tumors (N = 22), of whom 7 pts carried various FGFR genetic aberrations (GA), were enrolled at 2 dose levels (DL) (1200 mg AZB Q3W + 200 mg [DL1] / 300 mg [DL2] DZB QD) and treated until disease progression or unacceptable toxicity. Both DLs were divided into MTD (endpoint: dose-limiting toxicity [DLT] at D21) and expansion cohorts to investigate both acute and delayed adverse events (AEs) per CTCAE v5. Results: In the MTD cohorts of both DL1 (N = 7) and DL2 (N = 6) no DLTs were observed, and the DL1 and DL2 expansion cohorts subsequently enrolled 7 and 6 pts, respectively. The most frequent treatment-emergent AEs across both DLs were fatigue (31%), nausea (27%), diarrhea (23%), the most frequent laboratory abnormalities were increased ALT (58%), and AST (50%). Non-DLT grade (G) ≥ 3 treatment-related AEs (TRAE) across both DLs were G3 diarrhea (4%), G3 nausea (4%), G3 asthenia (4%), oral fungal infection (4%) and one case of immune-related G4 nephritis (4%). Dose interruptions / reductions and discontinuations due to TRAEs occurred in 19% and 8%, respectively. Pharmacokinetic analyses demonstrated that DZB exposure parameters and AZB serum concentrations in pts treated with DZB+AZB were similar to those assessed in pts under DZB / AZB monotherapy. At data cut-off, 2 of 14 (DL1) and 7 of 12 pts (DL2) were still on treatment. Median duration of treatment in DL1 was 9.7 weeks (range, 9-25), and best overall response per investigator assessment was SD in 4 of 10 efficacy-evaluable DL1 pts. DL2 efficacy analysis was uninformative at cutoff. The combination of 1200 mg AZB Q3W with both 200 mg and 300 mg QD DZB was found to be safe and tolerable. Conclusions: The combination of DZB+AZB is safe at both investigated DLs, the RP2D has been determined as 300 mg DZB QD+1200 mg AZB Q3W. DZB can be safely dosed at its monotherapy RP2D in this novel combination with AZB. The anti-tumor efficacy of DZB+AZB is currently being investigated in adequately designed cohorts of FIDES-02 with enrichment for UC pts with FGFR GA. Clinical trial information: NCT04045613.

Clinical and Epidemiologic Features of Visceral Leishmaniasis in Children: A 6-year Study from an Iranian Referral Hospital.

Visceral leishmaniasis (VL) is an emerging zoonosis disease that is endemic in the northwestern and southern part of Iran. This study aimed to evaluate the clinical characteristics and laboratory findings of the children with VL hospitalized at Children Medical Center Hospital (CMC), Tehran, Iran. A retrospective study was performed based on studied medical records of children with a final diagnosis of VL from 2011 to 2016. For each patient's demographics, clinical laboratory findings and treatment were examined. The clinical features of 17 children were examined and the most frequent symptoms were fever (94.1%, n=16), pallor, loss of appetite (76.5%, n=13), splenomegaly (82.4%, n=14) and hepatomegaly (58.8%, n=10). The most frequent laboratory abnormalities were hematological including anemia (94.1%, n=16), leukopenia (52.9%, n=9) and thrombocytopenia (70.5%, n=12). In order to detect anti-Leishmania antibodies, DAT was performed in 11 patients and 82% of them were positive (titers ≥ 1: 3200). In addition, rK39 was used in 9 cases and 7 children (78%) had positive results. Direct parasitology revealed the presence of amastigotes of Leishmania in bone marrow aspirate (BMA) stained by Giemsa stain in 9 patients (69%, among 13 children). Leishmaniasis is a regional disease therefore management and control of disease, particularly in an endemic area, as well as detection of new emerging foci are recommended.

Clinical analysis of macrophage activation syndrome in adult rheumatic disease: A multicenter retrospective study.

To evaluate the clinical and laboratory characteristics, prognostic factors, and outcome of adult rheumatic disease-associated macrophage activation syndrome (MAS). A multicenter retrospective study was performed across 4 tertiary hospitals in China between January 1, 2017 to December 31, 2019. There were 61 rheumatic disease patients with MAS enrolled into this retrospective clinical study. Fever and hyperferritinemia are the most frequent clinical feature and laboratory abnormality in MAS patients. Serum ferritin>6000ng/mL (odds ratio [OR]=9.46, 95% CI=2.53-47.13, P=.005) and hemophagocytosis in bone marrow smear (OR=11.12, 95%, CI=3.29-50.65, P=.001) were the 2 most prominent predictive factors indicating MAS occurrence. The 90-day all-cause mortality rate of all rheumatic disease patients with MAS was 22.9% (hazards ratio [HR]=2.15, 95% CI=0.81-6.78, P=.05). Platelets<100×109 /L (HR=3.23, 95% CI=2.51-4.81, P=.01) and ferritin>6000ng/mL (HR=6.12, 95% CI=2.93-16.27, P=.005) were independent predictors of poor outcome in rheumatic disease-associated MAS. Macrophage activation syndrome could be a fatal complication in rheumatic disease. Patients presenting with unexplained fever, serum ferritin>6000ng/mL, hepatosplenomegaly and cytopenia at baseline should raise the suspicion of MAS. The presence of serum ferritin>6000ng/mL, hepatosplenomegaly and low number of platelets was associated with poor outcome.

Nghiên cứu đặc điểm lâm sàng và cận lâm sàng bệnh schonlein-henoch ở trẻ em

Study clinical and subclinical features of Henoch-Schönlein purpura in children Objective: Describe clinical and subclinical characteristics of Henoch-Schönlein purpura in children. Find the relationship between kidney lesion and clinical and subclinical manifestations. Methods: Cross-sectional descriptive study, including 51 children &lt;15 years of age diagnosed with Schonlein-Henoch purpura being treated at Hue Central Hospital and Hue University Hospital from April 2016 - May 2018. Results: 51 children entered the study: Male:Female =1.3:1; mean age 7.5  3.4 years. At onset, purpura was present in all cases, gastrointestinal manifestations in 66.7%, arthritis/arthralgias in 54.9%, , renal lesion in 19.6%. The most frequent laboratory abnormalities were Leukocytosis (WBC &gt;10 x 109/L) in 60,8%, high-erythrocyte sedimentation rate (ESR) in 80.4%, microscopic hematuria in 15.7%, proteinuria in 13.7%. Renal lesion were correlated with age of onset. The age group&gt; 10 years old has 6.1 times more kidney lesion than the group ≤ 10 years (OR: 6.1; 95% CI (1.5-26). Conclusion: Clinical and subclinical findings of Schonlein-Henoch purpura in our study are similar to those in the literature. There is an relationship between the age of onset with kidney lesion. Key words: Henoch-Schönlein purpura, kidney lesion

Adverse effects of direct acting antiviral-based regimens in chronic hepatitis C patients: a Brazilian experience.

Background Direct-acting antivirals (DAA) are currently used for the treatment of chronic hepatitis C (HCV). However, few studies describe the adverse effects (AE) associated with DAA therapy in "real-word" cohorts. Aim To evaluate AE in Brazilian chronic HCV patients after DAA-therapy. Setting A reference center for hepatitis treatment in Rio de Janeiro, Brazil. Methods An observational "real-world" study was conducted with 102 chronic HCV patients undergoing DAA therapy for 12 or 24weeks. The self-reported AE were correlated with cirrhosis status, genotype, age, current therapeutic schemes and comorbidities. Serious AE were also investigated. Main outcome measure Frequency of AE during DAA therapy. Results Overall, mean±SD age was 60.9±9.4years, 67% were females, HCV-genotype 1 was the most prevalent (81%) and 74% were cirrhotic. Moreover, all patients reached sustained virological response. About 90% of patients reported at least one AE associated with current treatment, with a mean of 2.7 symptoms per patient. The most frequently reported AE were fatigue (43%), headache (42%), neuropsychiatric symptoms (30%) and nausea (26%). Furthermore, hemoglobin<12mg/dL was the most frequent (38%) laboratory abnormality observed. Neuropsychiatric symptoms were the only AE significantly different in treatment-experienced group when compared to naïve patients (41.7 vs. 12.5, P=0.002). The higher frequency of AE did not correlatewith the presence of previous treatment, cirrhosis, genotype, age, current therapeutic schemes with DAA or comorbidities. Conclusion DAA-based therapeutic regimens demonstrated safety in a Brazilian "real-world" cohort of chronic hepatitis C patients.

Safety of tocilizumab in the treatment of juvenile idiopathic arthritis

ABSTRACTIntroduction: Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody and IL-6 receptor antagonist, currently approved for the treatment of systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA) in children aged 2 years or older refractory to conventional treatment. The most common adverse events in patients treated with TCZ were infections, especially in the respiratory tract. The most frequent laboratory abnormalities were altered liver function, neutropenia and elevated cholesterol levels.Areas covered: The safety of TCZ in the treatment of children with JIA was determined based on a review of published clinical trials, including two multicenter studies of patients with sJIA and pJIA (the TENDER and CHERISH trials, respectively). The frequency of adverse events (AEs), serious adverse events (SAEs) and deaths reported in these studies was analyzed and discussed.Expert opinion: TCZ was effective and well tolerated in the treatment of severe forms of sJIA and pJIA, and can be considered a treatment of choice for these conditions. The risk of infections and laboratory abnormalities, such as neutropenia, should be constantly monitored. There is still a need for comparative studies of the risks and benefits of biological agents in patients with refractory JIA.

SEVERITY ASSESSMENT OF COMMUNITY9ACQUIRED PNEUMONIA IN REAL CLINICAL PRACTICE IN A MULTI9PROFILE HOSPITAL IN RUSSIA

We aimed to assess the criteria used by physicians in routine clinical practice to assess severity of communityacquired pneumonia (CAP) in adults. Methods. A survey of 165 physicians from multiprofile hospitals was performed at six Russian cities. Results. Chest Xray data were considered by 80% of respondents as an important marker to identify severe / non-severe CAP. Clinical features, comorbidity, laboratory abnormalities, and history data were noted by 78.8%; 66.1%; 55.8% and 23.6% of physicians, respectively. Severe dyspnea or tachypnea and confusion were the most often mentioned clinical criteria of severe CAP (78.8% of respondents for each, respectively). Lung tissue destruction was chosen as radiologic criterion of severe CAP in 80.6% of cases. Hyperleukocytosis and leukopenia were pointed as the most frequent laboratory abnormality related to severe CAP(89.7%). Only 10.3% of respondents used CAP prognostic scales. CAP prognostic scales recommended by national guidelines for adult patients (e.g. PORT и CURB/CRB65) were not usually used. Conclusion. Generally, physicians are aware of CAP prognostic criteria and key risk factors of poor prognosis. Additional efforts are needed for more efficient implementation of CAP prognostic scales recommended by national guidelines.

Frequent laboratory abnormalities in CIDP patients.

The role of screening laboratory tests in chronic inflammatory demyelinating polyneuropathy (CIDP) is currently unknown. The objectives of this study are to explore common laboratory test abnormalities in CIDP patients. CIDP subjects attending the Neuromuscular Clinic between 01/2013 and 12/2014 were evaluated. Demographic data, clinical history, physical examination, and laboratory test results were extracted from their charts. Seventy-nine charts were reviewed. Mean age was 61 ± 11 years. Most (84%) CIDP patients had laboratory test abnormalities; the most frequent were paraproteinemia (29%) and elevated HbA1C (28%) and creatine kinase (27%). Additional abnormalities included anemia in 19%, and elevated anti-neutrophil cytoplasmic antibody, erythrocyte sedimentation rate, and urate in 17%, elevated antinuclear antibodies, rheumatoid factor, and thyroid-stimulating hormone in 11%, and abnormal C3 in 10%. Laboratory test abnormalities were found in most CIDP patients. The most common were paraproteinemia, higher than expected frequency of diabetes, and unexpected CK elevation. Additional abnormalities included anemia, high urate levels, and common biomarkers for vasculitic neuropathies. Muscle Nerve 53: 862-865, 2016.

Platelets in Critical Illness

In patients with critical illness, thrombocytopenia is a frequent laboratory abnormality. However frequent this may occur, a low platelet count is not an epiphenomenon, but a marker with further significance. It is always important to assess the proper cause for thrombocytopenia in critically ill patients because different underlying disorders may precipitate different diagnostic and therapeutic management strategies. Platelets are part of the first-line defense of the body against bleeding; hence, thrombocytopenia may increase the risk of hemorrhage. In case of systemic inflammatory syndromes, such as the response to sepsis, disseminated intravascular platelet activation may occur. This will contribute to microvascular failure and thereby play a role in the development of organ dysfunction. Platelets are circulating blood cells that will normally not interact with the intact vessel wall but that may swiftly respond to endothelial disruption (which is often part of the pathogenesis of critical illness) by adhering to subendothelial structures, followed by interaction with each other, thereby forming a platelet aggregate. The activated platelet (phospholipid) membrane may form a suitable surface on which further coagulation activation may occur. A low platelet count is a strong and independent predictor of an adverse outcome in critically ill patients, thereby facilitating a simple and practically risk assessment in these patients and potentially guiding the use of complex or expensive treatment strategies.

Hashimoto encephalopathy: A study of the clinical profile, radiological and electrophysiological correlation in a Tertiary Care Center in South India.

Background:Hashimoto encephalopathy (HE) is a poorly understood and often misdiagnosed entity with variable clinical spectrum. There are many uncertainties that still remain about this condition and the pathological significance of thyroid peroxidase (TPO) antibody.Objective:To characterize the clinical, laboratory and radiologic findings in patients with HE.Design:Retrospective analysis of clinical features and diagnostic test data.Main Outcome Measures:Clinical features, laboratory, radiologic, electroencephalography (EEG) findings associated with HE and therapeutic outcome.Results:Thirteen consecutive patients were identified as having HE. The median age at onset was 48.5 years (range, 19–62 years). There was a female preponderance (76.9%). Clinical manifestations were cognitive impairment and behavioral changes in 10 (76.9%), sleep disturbance in 9 (69.2%), seizures in 6 (46.1%), headache in 4 (30.8%), psychosis or paranoia in 5 (38.5%), transient symptoms in 6 (46.1%), myoclonus in 4 (30.8%), ataxia or gait disorder in 4 (30.8%). The most frequent laboratory abnormalities were increased TPO (n = 13) in all cases, increased thyroid stimulating hormone levels (n = 6), and increased erythrocyte sedimentation rate (n = 5). The cerebrospinal fluid protein level was elevated in 8 of 9 patients (88.8%). Magnetic resonance imaging abnormalities were present in 2 patients (15.4%). EEG changes were seen in 7 patients (53.8%). All but two patients showed significant therapeutic benefit with steroids.Conclusions:HE has a wide range of clinical, laboratory, and radiologic findings. All patients with an unexplained encephalopathy should be screened for this condition as treatment response is excellent. To the best of our knowledge, this is the largest single center clinical series of HE from the Indian subcontinent.

Polymorphism of UGT1A1 and Frequency of Hyperbilirubinemia in Patients with Chronic Myeloid Leukemia Treated By Nilotinib

Background. Isolated hyperbilirubinemia mostly of indirect bilirubin fraction is diagnosed in patients with polymorphism of UGT1A1 gene (Gilbert’s syndrome), mainly homozygous genotype (TA)7/(TA)7 which encodes the enzyme uridinediphosphoglycosyltransferase 1 (UDP-GT) in hepatocytes. Hyperbilirubinemia is also frequent laboratory abnormality in chronic myeloid (CML) patients treated by nilotinib. Connection of hyperbilirubinemia with UGT1A1 polymorphism in CML patients on nilotinib therapy requires understanding and studying.Aims. To estimate the correlation between polymorphism of UGT1A1 gene and frequency of hyperbilirubinemia in patients with CML treated by nilotinib.Methods. We estimated biochemical parameters in a group of 100 patients treated by nilotinib: bilirubin, transaminases (AST, ALT), persistence of hyperbilirubinemia and biochemical parameters normalization. We also considered patients’ anamnesis for hepatitis and estimated those laboratory abnormalities in previous imatinib therapy as 98 of 100 patients received nilotinib second line after imatinib.Me time of observation on nilotinib therapy was 36.7 months (range 1 – 94.5).Men/women ratio was 45/55. Promoter region of the UGT1A1 gene was studied by allele specific polymerase chain reaction (AS-PCR).Results. Hyperbilirubinemia due to the indirect bilirubin fraction was observed in 84 (84%) of 100 patients. Of those 84 patients hyperbilirubinemia grade 1 was in 41 (49%), grade 2 in 33 (39%), grade 3 in 10 (12%). Normal genotype (TA)6/(TA)6 was in 71 (71%) patients, heterozygous genotype (TA)6/(TA)7 in 19 (19%), homozygous genotype (TA)7/(TA)7 in 10 (10%) patients. Frequency of hyperbilirubinemia grade 1-3 in patients depending on genotype is presented in table1. [Display omitted] Hyperbilirubinemia grade 1 was associated mostly with normal genotype patients, grade 2 with normal and abnormal genotype, grade 3 with abnormal and homozygous genotype (9 of 10 patients). In 1 patient with normal genotype grade 3 hyperbilirubinemia was due to intracellular hemolysis approved by laboratory tests. One patient with heterozygous form (TA6/TA7) and normal bilirubin was on nilotinib <1 month.Hyperbilirubinemia on previous imatinib treatment was in 29 (35,7%) of 82 patients with second line nilotinib: grade 1 in 25 (86.2%) of 29 patients (homozygous genotype TA7/TA7 in 5 of 25), grade 2 in 4 (13.8%) of 29 patients (all with homozygous genotype TA7/TA7). Normal bilirubin levels were in 55(46,3%) of 82 patients on previous imatinib therapy. One patient with TA7/TA7 genotype received nilotinib as first line.Bilirubin levels normalized in 48 (57.2%) of 84 patients during 1 to 3 months and persisted in 36 (42.8%).In 8(9,5%) of 84 patients transient ALT and AST elevation was observed: grade 1(1), grade 2 (5) grade 3-4(2); it was resolved and only isolated hyperbilirubinemia was observed later on. In 2 of 84 patients hepatitis C was diagnosed.No treatment discontinuation was done due to hyperbilirubinemia.Summary/Conclusion. In CML patients on nilotinib treatment Grade 3 hyperbilirubinemia as well as previous history of hyperbilirubinemia any grade on imatinib can be a sign of homozygous genotype TA7/TA7. Lower grades of hyperbilirubinemia occur both in patients with normal and abnormal heterozygous genotype. Other reasons for hyperbilirubinemia (hemolysis, hepatitis) should be assessed. No connection of UGT1A1 polymorphism and transaminase (ALT,AST) elevation was established. DisclosuresChelysheva:Bristol-Myers Squibb: Consultancy, Honoraria; Novartis International AG: Consultancy, Honoraria. Turkina:Bristol-Myers Squibb: Consultancy, Honoraria; Novartis International AG: Consultancy, Honoraria.

A Clinical Approach to Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) has a varying prevalence worldwide. The etiology behind this disease remains not fully understood with multiple factors influencing its development including genetic variations, dietary factors, hormonal changes, and environmental influences. Presenting mainly during the third trimester with generalized itching and resolving spontaneously postpartum, this condition is still associated with fetal morbidity and mortality. The diagnosis is based on clinical presentation in association with biochemical abnormalities. Elevation in total bile acid levels is the most frequent laboratory abnormality and seems to be the most important for gauging further management of the disease. The most appropriate gestational age for the delivery of women with ICP is yet to be determined. In this review we discuss the epidemiology, clinical features, diagnosis, etiology, and management of ICP, trying to shed light on some controversial aspects of the disease.

Aortic thrombosis in dogs: 31 cases (2000–2010)

To describe clinical signs, treatment, and outcome of aortic thrombosis in dogs. Retrospective case series. 31 dogs with aortic thrombosis. Records were retrospectively reviewed and data collected regarding signalment, historical signs, physical examination findings, laboratory testing, definitive diagnosis, and presence of concurrent disease. The records of 31 dogs with clinical or postmortem diagnosis of aortic thrombosis were reviewed. Onset of clinical signs was acute in 14 (45%) dogs, chronic in 15 (48%), and not documented in 2 (6%). Femoral pulses were subjectively weak in 6 (19%) dogs and absent in 17 (55%). Frequent laboratory abnormalities included high BUN concentration (n = 13), creatinine concentration (6), creatine kinase activity (10), and D-dimer concentration (10) and proteinuria with a urine protein-to-creatinine concentration ratio > 0.5 (12). Concurrent conditions included neoplasia (n = 6), recent administration of corticosteroids (6), and renal (8) or cardiac (6) disease. Median survival time was significantly longer for dogs with chronic onset of disease (30 days; range, 0 to 959 days) than for those with acute onset of clinical signs (1.5 days; range, 0 to 120 days). Results suggested that aortic thrombosis is a rare condition in dogs and accounted for only 0.0005% of hospital admissions during the study period. The clinical signs for dogs with aortic thrombosis differed from those seen in feline patients with aortic thromboembolism. Median survival time was significantly longer for dogs with chronic disease than for dogs with acute disease. Despite treatment, outcomes were typically poor, although protracted periods of survival were achieved in some dogs.