LC-MS/MS quantification of olanzapine in hair after alkaline digestion.

Olanzapine (OLZ), a second-generation antipsychotic drug, is effective in the treatment of acute psychosis, schizophrenia, agitation, bipolar mania, and other psychiatric problems. Antipsychotics are prescribed drugs, which lead the drug abuser to illegal methods of access. This behavior also demonstrates the association of OLZ with criminal involvement, commonly observed at forensic crime scenes. The acute toxicity and even death resulting from OLZ exposure have been highlighted in numerous studies. Therefore, developing analytical techniques to detect OLZ is essential for forensic toxicology. This study aimed to develop a specific and reliable LC-MS/MS method for OLZ detection and quantification in hair samples. The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), trueness, precision, and uncertainty. The range of linearity was between 0.1-100 ng/mg, with LOD and LOQ values established at 0.036 ng/mg and 0.1 ng/mg, respectively. All validation results are within acceptable parameters. The validated method has been applied to authentic hair samples. The variation of OLZ concentrations in 12 hair segments (2 from Case 1 and 10 from Case 2) from two drug-positive patients, ranging from 0.131 to 0.460 ng/mg, is presented in this study. Although several studies have been conducted to determine OLZ in hair samples using segmental analysis via hair solubilization, this study is the first to determine OLZ in hair samples after "digestion" with comparative parameters prior to chromatographic analysis.

A novel homozygous SLC12A3 mutation causing Gitelman syndrome with co-existent autoimmune thyroiditis: a case report and review of the literature.

Gitelman syndrome is a rare, autosomal recessively inherited tubulopathy manifesting with hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Common symptoms include fatigue, myalgia, reduced performance capacity, tetany, paresthesia, and delayed growth. However, as reported in the literature, diagnosis in some patients is prompted by an incidental finding of hypokalemia. GS develops due to mutations in the SLC12A3 gene, which encodes the thiazide-sensitive Na-Cl cotransporter. Many variants in the SLC12A3 gene causing GS have been reported in literature. A new pathogenic homozygous mutation (c.2612G > T), absence of hypomagnesemia, and accompanying autoimmune thyroiditis are remarkable in our patient. There are a few Gitelman syndrome cases that are complicated with autoimmune thyroiditis in the literature. In this study, we present a case of Gitelman syndrome with a novel homozygous mutation and accompanying autoimmune thyroiditis and review of the literature.

How to recognize and manage challenging DRESS cases: Two case reports and a review of the literature.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon systemic adverse drug reaction. Furthermore, it is a unique syndrome encompassing various manifestations of fever, facial edema, eosinophilia, atypical lymphocytosis, and organ dysfunction. Since there are no large prospective studies concerning DRESS syndrome, current treatment modalities for DRESS have been mainly determined based on various case reports and expert opinions. Corticosteroids are the mainstay of therapy after the cessation of the culprit drug. Although most cases recover within a couple of months, some may persist and even progress despite 1 mg/kg/day of prednisolone or its equivalent. We herein present two cases of severe DRESS syndrome. Both cases presented with organ dysfunction and remained unresponsive to initial treatment with 1 mg/kg/day of intravenous methylprednisolone. Therefore, plasmapheresis or pulse steroid therapy (250 mg/day methylprednisolone for 3 days) was used. In the follow-up period, the patients' clinical conditions improved dramatically without recurrence. We aimed to share our experience in recognizing and managing severe DRESS cases in this manuscript. Furthermore, we reviewed the literature in comparison with the present cases. In conclusion, plasmapheresis or pulse steroid therapy (250 mg/day of methylprednisolone for 3 days) can be used to treat difficult DRESS cases where organ failure is about to happen.

Omental infarction in mild Covid-19 infection.

COVID-19 is an infection which can present with various clinical manifestations. While it affects respiratory tract primarily, several other manifestations including gastrointestinal involvements have been reported. The prevalence of all gastrointestinal complaints is approximately 17 percent and diarrhea, nausea/vomiting and abdominal pain are the most common symptoms. In COVID-19, acute abdominal pain requiring surgical evaluation and abdominal imaging is uncommon and there is also a lack of knowledge about COVID-19 related gastrointestinal complications. Here, we report a case of mild COVID-19 infection complicated by omental infarction during the course of the illness.

Tocilizumab in COVID-19: The Cerrahpasa-PREDICT score.

BACKGROUND: Cytokine release syndrome (CRS), characterized by overproduction of proinflammatory cytokines in the course of severe coronavirus disease 2019 (COVID-19), has been suggested as the major cause of mortality. Tocilizumab, a recombinant humanized monoclonal antibody against human IL-6 receptor, poses a therapeutic option for the treatment of CRS leading to severe acute respiratory syndrome in coronavirus-2 (SARS-CoV-2) infection. METHODS: We performed a single-center retrospective study to reveal the outcome of COVID-19 patients on tocilizumab and proposed "the Cerrahpasa-PREDICT score", a new clinical scoring system using clinical and laboratory parameters that would help predicting the 28-day mortality of COVID-19 patients receiving tocilizumab. RESULTS: Eighty-seven patients (median age: 59 years) were included of whom 75.8% were male. Tocilizumab use significantly improved clinical and laboratory parameters. The 28-day mortality rate on tocilizumab was 16.1%. The Cerrahpasa-PREDICT score, consisting of platelet counts, procalcitonin, D-dimer levels, SO2R and the time from symptom onset to tocilizumab administration had a positive predictive value of 94.5% and negative predictive value of 92.9% for anticipating 28-day mortality. CONCLUSIONS: Severe COVID-19 should closely be monitored for the signs of hyperinflammation. We showed that administration of tocilizumab early in the course of the disease (prior to ICU admission) resulted in a favorable outcome. Close monitoring usually aids identifying patients who would benefit from tocilizumab. In this regard, the Cerrahpasa-PREDICT score might serve as a practical tool for estimating the 28-day mortality in COVID-19 patients who received tocilizumab and would facilitate timely recognition of fatal cases to be evaluated for other therapeutic options.

How to treat myelodysplastic syndrome with clinical features resembling Behçet syndrome: a case-based systematic review.

The association between myelodysplastic syndrome (MDS) and Behçet syndrome (BS) is recognized for over 25 years. High frequency of trisomy 8 and intestinal ulcers are striking features of this association. There are no recommendations for how these patients should be treated. A systematic literature review was performed in PubMed using the keyword combination "(((((intestinal) OR gastrointestinal) OR ulcer) OR Behcet*)) AND ((myelodysplastic syndrome) OR MDS)" in March 2019. Our aim was to gain insight regarding clinical responses to individual treatment modalities. A recent case was also presented and included in the analysis. Data from 41 articles reporting on a total of 53 patients carried adequate information to assess treatment responses. Glucocorticoids provided benefit in 23 of 43 patients. Azacitidine, decitabine, thalidomide, and cyclosporine contributed to a clinical improvement in 4/6, 2/3, 3/4, and 5/8 patients respectively. Hematopoietic stem cell transplantation was successful in 9 of 13 patients. With the use of TNF inhibitors, azathioprine, and mesalamine derivatives, clinical improvement was observed in 3/11, 0/4, and 6/18 patients respectively. Patients with MDS and BS-like features who are resistant to glucocorticoids have so far benefited more from treatment approaches directed at MDS, rather than the immunosuppressive agents used for BS.

The role of TMPRSS6 gene variants in iron-related hematological parameters in Turkish patients with iron deficiency anemia.

TMPRSS6 gene mutations can result in iron deficiency anemia (IDA) and cause an increased iron-regulatory hormone, hepcidin, levels. TMPRSS6 encodes a serine protease, matriptase-2, which functions as negative regulatory protein of hepcidin transcription. Thus, TMPRSS6 variations might be risk factors for IDA. The aim of the study was to investigate the association of rs855791, rs4820268, rs5756506, rs2235324, rs2413450, rs2111833, rs228919, and rs733655 SNPs in TMPRSS6 gene with IDA susceptibility and iron-related clinical parameters. The study consisted of 150 IDA patients and 100 healthy controls. We analyzed the genotype distributions by using Real-Time polymerase chain reaction (Real-Time PCR) technique. We did not find any statistically differences for all SNPs between patients and controls (P > 0.05). In IDA patients, variations rs855791 and rs2413450 were associated with increased RBC (P = 0.03) and TIBC (P = 0.04), respectively. Also, increased of TIBC for rs4820268 (P < 0.05). On the other hand, in control group, rs5756506 was associated with two parameters, Hb (P = 0.02) and Hct (P = 0.03). We did not find markedly hepcidin levels in IDA patients compared to controls (P = 0.32). Our findings suggest that TMPRSS6 variations may not be risk factors for IDA. However, TMPRSS6 polymorphisms are associated with increased many iron-related hematological parameters.

The impact of protein oxidation on sustained and white coat hypertension.

OBJECTIVE: The present study compared the unfavorable effects of protein oxidation and deoxyribonucleic acid damage on patients with white coat hypertension (WCH), sustained hypertension (HT), and normotensives. METHODS: Participants were allocated into 3 groups: 40 healthy controls, 36 patients with WCH, and 40 patients with sustained HT. Patients with risk factors for atherosclerosis, endocrine diseases, alcoholism, or masked hypertension were excluded. Plasma level of protein carbonyl (PCO), ischemia modified albumin (IMA), total thiol (T-SH), prooxidant-antioxidant balance (PAB), advanced protein oxidation products (AOPPs), and urinary level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured and relationship between these oxidative stress parameters and WCH and sustained HT was analyzed. RESULTS: Ambulatory 24-hour, daytime and night-time systolic and diastolic blood pressure readings of sustained HT group were significantly higher than those of WCH and control groups (p<0.001, all). AOPPs, PCO, IMA, 8-OHdG, and PAB levels were significantly higher in HT group than WCH and control groups (p<0.001, all). Additionally, T-SH level was significantly lower in HT group than WCH and control groups (p<0.001). A similar statistically significant relationship was detected between WCH and control groups. CONCLUSION: Results indicate that increased level of AOPPs, PCO, IMA, 8-OHdG, PAB, and decreased level of T-SH are likely to be indicators of oxidative stress, which may play a key role both in WCH and sustained HT.

Oxidative stress parameters and inflammatory and immune mediators as markers of the severity of sepsis.

INTRODUCTION: Sepsis is a complex inflammatory syndrome with diverse etiology and wide spectrum of severity. The aim of this study was to investigate whether inflammatory mediators, in comparison with oxidative parameters, are associated with severity of sepsis. METHODOLOGY: Plasma neopterin, adenosine deaminase (ADA), vascular cell adhesion molecule (VCAM), intracellular adhesion molecule (ICAM), interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNF-α), as inflammatory mediators, and serum nitric oxide (NOx), nitrotyrosine (NT), oxidized LDL (oxLDL) levels, serum paraoxonase 1 (PON1) activity, and erythrocyte glutathione (GSH) levels as oxidative stress parameters of 12 patients with mild sepsis, 25 patients with severe sepsis, and 20 healthy control subjects were evaluated. NOx, GSH levels and PON1 activity were determined by colorimetric methods, whereas neopterin, VCAM, ICAM, IL-1, IL-6, TNF-α, NT, and oxLDL levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: All parameters in mild and severe sepsis were significantly different from those of healthy subjects, except ADA activities. Patients with severe sepsis exhibited higher IL-6, TNF-α, NT, and oxLDL levels than patients with mild sepsis. GSH (98%, 98%), oxLDL (98%, 98%), VCAM-1 (99%, 99%), and ICAM-1 (99%, 99%) have much more sensitivitiy and specificity in sepsis. CONCLUSIONS: Our results suggest that the oxidative stress and inflammatory response in patients with sepsis were increased and that serum IL-6, TNF-α, NT, and oxLDL levels were correlated with the severity of sepsis. Therefore, increases in these parameters may contribute to the dysfunction or failure of one or more organs, or even death, in sepsis.

Oleander Poisoning as an Example of Self-Medication Attempt.

BACKGROUND: There is an increasing interest in herbal products as a self-medication method in recent years. Some plant extracts either turn into drugs over time or are consumed directly without treatment. One of these plants is Nerium oleander L., which is a potentially lethal plant, since it has cardiac glycosides. However, numerous researches of its extracts have been performed against cancer cell lines in recent literature. This contradiction leads to misinterpretation and induces the prevalence of intoxication or fatal cases. CASE REPORT: This case is associated with an oleander-poisoned patient, who was admitted to the Emergency unit 20 hours after the first dose, and 8 hours after the second dose. Although she lives in a metropolis and has a higher level of education and numerous hospital facilities available, she had decided to take self-medication for her Hashimoto's thyroiditis and malignant thyroid disease which was caused by her apprehensive thoughts. Oleandrin was detected in the urine at a concentration of 3.2 ng/mL and in the serum at a concentration of 8.4 ng/mL by chromatographic analysis at the time of admission. CONCLUSION: This case represents the misunderstanding of herbal treatments by the community. Promoting awareness of the potential toxicity of this plant among the public may help to reduce the incidence of poisoning due to Nerium species.

Congenital Dyserythropoietic Anemia Type 1: Report of One Patient and Analysis of Previously Reported Patients Treated with Interferon Alpha.

Congenital dyserythropoietic anemias are a rare group of inherited anemias characterized by ineffective erythropoiesis and distinct morphological abnormalities in the erythroblasts. Interferon alpha has been shown to be effective in type 1 congenital dyserythropoietic anemia but the optimal duration of therapy is undefined. We present here a 32-years-old female patient diagnosed with type 1 congenital dyserythropoietic anemia precipitated by pregnancy and treated successfully with a short course of interferon alpha resulting in a durable response. A literature search including PubMed database on previously published articles regarding congenital dyserythropoietic anemia type 1 patients treated with interferon is conducted.

Treatment of patients with immune thrombocytopenia admitted to the emergency room.

Immune thrombocytopenia (ITP) is the most frequent cause of acquired thrombocytopenia. In adult ITP patients, corticosteroids and intravenous immunoglobulin (IVIg) are used as first-line treatment. The aim of the present study was to investigate retrospectively the demographic and etiologic characteristics of patients with ITP admitted to the emergency room at our hospital. Seventy-five adult patients with ITP were included, and demographic data, bleeding characteristics, etiologic features and responses to treatments were evaluated retrospectively. Fifty-six patients (75 %) were female, and the median age was 43 years. Eighteen patients had a history of ITP, whereas in 57, thrombocytopenia was identified for the first time. During admission, the median platelet count was 5 × 10(9)/L. Cutaneous and/or mucosal bleeding was the most common clinical feature. High-dose dexamethasone was administered in 60 episodes, whereas IVIg and conventional-dose methylprednisolone were used in nine and six episodes, respectively. The overall response rate of the entire cohort following first-line treatments was 67 %, and complete remission was achieved in 31 patients, 19 patients achieved partial remission, and 25 patients were non-responders. In cases with life-threatening bleeding, concomitant infection, post-traumatic bleeding and need for emergency surgery, IVIg can be used as the first line of treatment option in addition to platelet transfusions.

Acute generalized exanthematous pustulosis after ceftriaxone use resembling sepsis.

Acute generalized exanthematous pustulosis is an uncommon disorder, characterized by the acute onset of multiple pruritic, small, nonfollicular, sterile, superficial pustules over erythematous and edematous skin. It is frequently caused by medications, mainly antibiotics, and particularly beta-lactams. It is a rare condition that is not well known in infectious disease practice. We report a case of ceftriaxone-induced acute generalized exanthematous pustulosis that presented with the appearance of sepsis. After discontinuation of ceftriaxone, the findings were improved.

Native triple-valve endocarditis caused by penicillin-resistant Streptococcus sanguis.

BACKGROUND: A 26-year-old man with known but untreated ventricular septal defect was admitted to the emergency ward with abdominal pain, fever and weight loss. Transthoracic echocardiography showed multiple vegetations on the anterior mitral leaflet, a mobile vegetation on the surface of the aortic noncoronary cusp and another on the tricuspid valve. His blood cultures grew Streptococcus sanguis with a penicillin minimum inhibitory concentration of 3 microg/ml. INVESTIGATIONS: Physical examination, echocardiography, blood cultures, minimal inhibitory concentration detection. DIAGNOSIS: Multivalvular infective endocarditis caused by S. sanguis with a high penicillin resistance. MANAGEMENT: A combination of intravenous vancomycin and gentamicin, followed by early surgery.

Selective jejunal artery pseudoaneurysm embolization in a patient with massive gastrointestinal bleeding due to intestinal tuberculosis.

Gastrointestinal bleeding is a life-threatening manifestation of intestinal tuberculosis that is generally attributed to oozing of blood from the mucosal ulcers. We report a case of intestinal tuberculosis presenting with massive upper gastrointestinal bleeding from jejunal artery pseudoaneurysm diagnosed with angiography and successfully embolizated by histoacril (glue).

Simultaneous rupture of the liver and spleen in a patient on warfarin therapy: report of a case.

Although there are many reports describing spontaneous rupture of either the spleen or the liver, the simultaneous rupture of both organs is a rare event, especially during anticoagulant therapy. We report a case of spontaneous rupture of the spleen and liver in a patient on warfarin therapy for deep venous thrombosis.