Patient with Jaundice, Dyspnea and Hyperferritinemia after COVID-19

The aim: to highlight the importance of considering hemophagocytic lymphohistiocytosis in patients with jaundice of unclear origin and systemic inflammatory manifestations after coronavirus infection.Key points. A 64-y.o. patient was admitted to the hospital with jaundice, pruritus, fatigue, weight loss. The complaints occurred 2 weeks after discharge from the hospital for treatment of patients with coronavirus infection. Laboratory tests revealed signs of hepatic insufficiency, markers of cholestasis and inflammation persisted in time. Upon instrumental examination no signs of hepatosplenomegaly, biliary tree changes, intra- and extrahepatic obstruction were found. S. aureus was identified in blood cultures, CT scan of the facial skull bones showcased the focus of infection in the area of the roots of teeth 2.4 and 2.5. Therefore, antibiotics were prescribed. Subsequently, the patient's condition was complicated by the development of two episodes of acute respiratory distress syndrome, which occurred during the withdrawal of glucocorticosteroid therapy. Liver biopsy was performed, morphological study revealed signs of “vanishing bile duct” syndrome, excessive activation of macrophages and hemosiderosis of sinusoidal cells. Identified lesions can be found in hemophagocytic lymphohistiocytosis (HLH), a life-threatening complication of coronavirus infection. Glucocorticosteroids therapy, transfusions of human immunoglobulin, albumin, and parenteral nutrition have led to patient's condition improvement.Conclusion. COVID-19 provokes the development of secondary HLH 10 times more often than other respiratory viral infections. The possibility of hemophagocytic syndrome development should be considered, including cases of overlap syndrome with sepsis, in patients with unresolved jaundice, hyperferritinemia after coronavirus infection. Routinely used scales and criteria for diagnosis of HLH (H-score, HLH 2004) in such cases lacks sensitivity, therefore, careful analysis of clinical picture and exclusion of other causes of jaundice are required

The cytokine profile change in patients with genital herpes during relapse

47 patients of the main group and 24 conventionally healthy men (the control group) were examined to establish the characteristic features of cytokine profile change in patients with genital herpes during relapse. The concentration of cytokines (IL-1p, IL-4, IL-6 and TNFa) in patients blood serum was assessed using conventional methods. The correlation between the levels of pro-inflammatory and anti-inflammatory cytokines and the clinical features of the relapse course were established.С целью выявления характера изменений профиля цитокинов у больных генитальным герпесом в период рецидива были обследованы 47 пациентов, составивших основную группу, и 24 условно здоровых мужчины (группа сравнения). У всех пациентов оценивалась концентрация цитокинов в сыворотке крови (ИЛ-1р, ИЛ-4, ИЛ-6, ФНО-а) по общепринятым методикам. В результате проведенного исследования была выявлена взаимосвязь между уровнем провоспалительных и противовоспалительных цитокинов и характером течения рецидива

Применение гуселькумаба при псориатическом артрите: данные реальной клинической практики

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, spine and enthesis from the group of spondyloarthritis that develops in patients with psoriasis. Guselkumab is a biologic disease-modifying antirheumatic drug, an inhibitor of interleukin 23, which has been shown to be effective in the treatment of plaque psoriasis and PsA.Objective: to evaluate the effectiveness of guselkumab treatment in PsA patients.Patients and methods. The study included 16 patients with PsA. All patients received 100 mg of guselkumab subcutaneously at weeks 0, 4, 12, 20. Disease activity and treatment efficacy were assessed at weeks 0, 12 and 24 using the DAS28, ASDAS, BASDAI, DAPSA activity indices, the index of the extent and severity of psoriasis PASI.Results and discussion. During treatment, patients with PsA showed a pronounced positive dynamics of the indices of disease activity and an improvement in the skin condition. Before the treatment with guselkumab, the mean value of the DAS28 index was 4.26±0.64, DAPSA – 37.94±9.45, ASDAS – 2.7±0.65, and BASDAI – 5.49±1.39, after 12 weeks of treatment these indicators decreased to 3.03±0.49; 17.06±4.58; 1.64±0.33 and 3.48±0.66, respectively, and after 24 weeks (after the 4th injection) – to 2.32±0.18; 11.31±2.18; 1.22±0.27 and 2.62±0.78, respectively (p<0.05 for all cases). Before treatment, the average PASI index reached 30.99±15.43, after 12 weeks – 4.55±4.82, and after 24 weeks – 1.05±1.46 (p<0.05). During treatment, a significant improvement in the main manifestations of the disease was noted: regression of peripheral arthritis, spondylitis, and skin rashes.The treatment was well tolerated during the 24 weeks of the study, and no serious adverse events were reported.Conclusion. The data from real clinical practice indicate that guselkumab is highly effective and safe in the treatment of PsA.Псориатический артрит (ПсА) – хроническое воспалительное заболевание суставов, позвоночника и энтезисов из группы спондилоартритов, развивающееся у больных псориазом. Гуселькумаб – генно-инженерный биологический препарат, ингибитор интерлейкина 23, показавший эффективность в терапии бляшечного псориаза и ПсА.Цель исследования – оценка эффективности лечения гуселькумабом больных ПсА.Пациенты и методы. В исследование включено 16 пациентов с ПсА. Все пациенты получали гуселькумаб в дозе 100 мг подкожно на неделях 0, 4, 12, 20. Оценка активности заболевания и эффективности лечения осуществлялась на неделях 0, 12 и 24 с применением индексов активности DAS28, ASDAS, BASDAI, DAPSA, индекса распространенности и тяжести псориаза – PASI.Результаты и обсуждение. В ходе лечения у больных ПсА наблюдались выраженная положительная динамика индексов активности заболевания и улучшение состояния кожи. Если до начала лечения гуселькумабом среднее значение индекса DAS28 составляло 4,26±0,64, DAPSA – 37,94±9,45, ASDAS – 2,7±0,65 и BASDAI – 5,49±1,39, то через 12 нед произошло снижение этих показателей до 3,03±0,49; 17,06±4,58; 1,64±0,33 и 3,48±0,66 соответственно, а через 24 нед (после 4-й инъекций) – уже до 2,32±0,18; 11,31±2,18; 1,22±0,27 и 2,62±0,78 соответственно (p<0,05 для всех случаев). До начала лечения среднее значение индекса PASI достигало 30,99±15,43, через 12 нед – 4,55±4,82 и через 24 нед – 1,05±1,46 (p<0,05). На фоне лечения отмечено значительное улучшение основных проявлений заболевания: регресс периферического артрита, спондилита и кожных высыпаний.На протяжении 24 нед исследования переносимость терапии была хорошей, серьезных нежелательных явлений не зарегистрировано.Заключение. Данные, полученные в условиях реальной клинической практики, свидетельствуют о высокой эффективности и безопасности гуселькумаба при лечении ПсА

Experience of using different schemes corticosteroid therapy for epileptic encephalopathies in children

The article presents the experience of using pulse therapy with dexamethasone and methylprednisolone in the treatment of epileptic encephalopathy on the basis of a prospective study of patients.В статье представлен опыт применения пульс-терапии дексаметазоном и метилпреднизолоном в лечении эпилептических энцефалопатий на основании проспективного исследования пациентов

Аутоиммунные поражения печени у пациентов с болезнью Шёгрена, ассоциированной с антицентромерными антителами

Objective: to determine the frequency, spectrum and severity of liver affection in anti-centromere antibodies (ACA) positive patients with primary Sjogren's syndrome (pSS).Patients and methods. 119 ACA-positive patients with pSS were included in the study, 37 (31%) of them had signs of liver damage, 3 of these patients were excluded from the study (2 had cholelithiasis, 1 had viral hepatitis B). Signs of autoimmune liver damage were found in 34 (28.6%) patients, most of them were seropositive for antimitochondrial antibodies (AMA). The diagnosis of primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) was established according to the recommendations of the American Association for the Study of Liver Diseases, the Russian Gastroenterological Association and the Russian Society for the Study of the Liver. In 5 (14.7%) patients the cause of cholestasis remained unspecified.Results and discussion. AMA were found in 73.5% of patients, elevated serum IgM levels – in 57.6%. Clinically liver damage in most cases was characterized by an asymptomatic, slowly progressive course without a dramatic increase of symptoms over time. Liver cirrhosis was found in 14.7% of patients. According to clinical, laboratory and morphological manifestations, PBC was diagnosed in 21 patients, 4 of them also had a cross syndrome with AIH. AMA-negative PBC was found in 3 patients and isolated AIH – in 1. In most cases, histological stage I of PBC was detected. During follow-up, median of 7 years (range from 2 to 15 years), in 7 patients with stage I PBC and in 7 AMA-positive patients without functional liver disorders no clinical, laboratory or instrumental progression of liver damage was noted. In this regard, it was suggested that these patients have epitheliitis of the biliary ducts as manifestation of glandular affection in pSS, and not true PBC.Conclusion. Autoimmune liver lesions are detected in 28.6% of ACA-positive patients with pSS, most (41.2%) of them develop epitheliitis of the biliary ducts as pSS manifestation or a combination of pSS with PBC (with the same frequency), less often PBC / AIH cross syndrome is diagnosed. PBC / pSS-related epitheliitis of the biliary ducts in ACA-positive patients is characterized by a slowly progressive asymptomatic course in most cases and rarely leads to the development of liver cirrhosis.Цель настоящего исследования – определить частоту, спектр и тяжесть течения поражений печени у позитивных по антицентромерным антителам (АЦА) пациентов с болезнью Шёгрена (БШ).Пациенты и методы. У 37 (31%) из 119 включенных в исследование АЦА-позитивных пациентов с БШ при обследовании выявлены признаки поражения печени, 3 из них были исключены из исследования (у 2 имелась желчнокаменная болезнь, у 1 – вирусный гепатит В). Признаки аутоиммунного поражения печени обнаружены у 34 (28,6%) больных, большинство из которых были серопозитивны по антимитохондриальным антителам (АМА). Диагноз первичного билиарного холангита (ПБХ) и аутоиммунного гепатита (АИГ) устанавливался согласно рекомендациям Американской ассоциации по изучению заболеваний печени, Российской гастроэнтерологической ассоциации и Российского общества по изучению печени. Причина холестаза у 5 (14,7%) пациентов осталась неуточненной.Результаты и обсуждение. АМА обнаружены у 73,5% пациентов, повышение уровня IgM – у 57,6%. Клинически поражение печени в большинстве случаев характеризовалось бессимптомным медленно прогрессирующим течением, как правило, без выраженного нарастания симптомов в динамике. Признаки цирроза выявлены у 14,7% пациентов. На основании клинико-лабораторно-морфологических проявлений ПБХ диагностирован у 21 больного, у 4 из которых также имелся перекрестный синдром с АИГ. АМА-негативный ПБХ установлен у 3 пациентов и изолированный АИГ – у 1. В большинстве случаев определялась I гистологическая стадия ПБХ. При динамическом наблюдении, медиана которого составила 7 лет (мин. 2 года, макс. 15 лет), у 7 пациентов с I стадией ПБХ и у 7 АМА-позитивных больных без функциональных нарушений печени в течение всего периода наблюдения клинического и лабораторно-инструментального прогрессирования поражения печени не отмечено. В связи с этим сделано предположение, что у данных пациентов имеется эпителиит билиарных протоков как проявление железистых поражений при БШ, а не истинный ПБХ.Заключение. Аутоиммунные поражения печени выявляются у 28,6% АЦА-позитивных пациентов с БШ, у большинства из них с одинаковой частотой (41,2%) развиваются эпителиит билиарных протоков в рамках БШ либо сочетание БШ с ПБХ, реже диагностируется перекрестный синдром ПБХ/АИГ. ПБХ/эпителиит билиарных протоков в рамках БШ у АЦА-позитивных пациентов в большинстве случаев характеризуется медленно прогрессирующим бессимптомным течением и редко приводит к развитию цирроза печени

The Palomar Testbed Interferometer Calibrator Catalog

The Palomar Testbed Interferometer (PTI) archive of observations between 1998 and 2005 is examined for objects appropriate for calibration of optical long-baseline interferometer observations - stars that are predictably point-like and single. Approximately 1,400 nights of data on 1,800 objects were examined for this investigation. We compare those observations to an intensively studied object that is a suitable calibrator, HD217014, and statistically compare each candidate calibrator to that object by computing both a Mahalanobis distance and a Principal Component Analysis. Our hypothesis is that the frequency distribution of visibility data associated with calibrator stars differs from non-calibrator stars such as binary stars. Spectroscopic binaries resolved by PTI, objects known to be unsuitable for calibrator use, are similarly tested to establish detection limits of this approach. From this investigation, we find more than 350 observed stars suitable for use as calibrators (with an additional $\approx 140$ being rejected), corresponding to $\gtrsim 95$ sky coverage for PTI. This approach is noteworthy in that it rigorously establishes calibration sources through a traceable, empirical methodology, leveraging the predictions of spectral energy distribution modeling but also verifying it with the rich body of PTI's on-sky observations.Comment: 100 pages, 7 figures, 7 tables; to appear in the May 2008ApJS, v176n

Structure and function analyses of the purified GPCR human vomeronasal type 1 receptor 1

The vomeronasal system is one of several fine-tuned scent-detecting signaling systems in mammals. However, despite significant efforts, how these receptors detect scent remains an enigma. One reason is the lack of sufficient purified receptors to perform detailed biochemical, biophysical and structural analyses. Here we report the ability to express and purify milligrams of purified, functional human vomeronasal receptor hVN1R1. Circular dichroism showed that purified hVN1R1 had an alpha-helical structure, similar to that of other GPCRs. Microscale thermophoresis showed that hVN1R1 bound its known ligand myrtenal with an EC50 ∼1 µM. This expression system can enable structural and functional analyses towards understanding how mammalian scent detection works

Impact of severity, duration, and etiology of hyperthyroidism on bone turnover markers and bone mineral density in men

<p>Abstract</p> <p>Background</p> <p>Hyperthyroidism is accompanied by osteoporosis with higher incidence of fracture rates. The present work aimed to study bone status in hyperthyroidism and to elucidate the impact of severity, duration, and etiology of hyperthyroidism on biochemical markers of bone turnover and bone mineral density (BMD).</p> <p>Methods</p> <p>Fifty-two male patients with hyperthyroidism, 31 with Graves' disease (GD) and 21 with toxic multinodular goiter (TNG), with an age ranging from 23 to 65 years were included, together with 25 healthy euthyroid men with matched age as a control group. In addition to full clinical examination, patients and controls were subjected to measurement of BMD using dual-energy X-ray absorptiometery scanning of the lower half of the left radius. Also, some biochemical markers of bone turnover were done for all patients and controls.</p> <p>Results</p> <p>Biochemical markers of bone turnover: included serum bone specific alkaline phosphatase, osteocalcin, carboxy terminal telopeptide of type l collagen also, urinary deoxypyridinoline cross-links (DXP), urinary DXP/urinary creatinine ratio and urinary calcium/urinary creatinine ratio were significantly higher in patients with GD and TNG compared to controls (P < 0.01). However, there was non-significant difference in these parameters between GD and TNG patients (P > 0.05). BMD was significantly lower in GD and TNG compared to controls, but the Z-score of BMD at the lower half of the left radius in patients with GD (-1.7 ± 0.5 SD) was not significantly different from those with TNG (-1.6 ± 0.6 SD) (>0.05). There was significant positive correlation between free T3 and free T4 with biochemical markers of bone turnover, but negative correlation between TSH and those biochemical markers of bone turnover. The duration of the thyrotoxic state positively correlated with the assessed bone turnover markers, but it is negatively correlated with the Z-score of BMD in the studied hyperthyroid patients (r = -0.68, P < 0.0001).</p> <p>Conclusion</p> <p>Men with hyperthyroidism have significant bone loss with higher biochemical markers of bone turnover. The severity and the duration of the thyrotoxic state are directly related to the derangement of biochemical markers of bone turnover and bone loss.</p