Vol 46, No 2 (2018)


Maternal and fetal effects of analgesia and anesthesia in spontaneous labor

Upriamova E.Y., Shifman E.M., Ovezov A.M., Novikova S.V., El'chaninova A.G., Chaplygina O.V.


Labor analgesia is an important aspect of obstetrics, because it significantly influences the process, quality, result and costs of medical management of labor and delivery. From this perspective, one of the most urgent and not fully resolved issues, that requires further studies, is the efficacy and safety of anesthesiological management of spontaneous vaginal delivery. The review presents detailed information on the effects of labor pain on the fetus and on pathophysiological characteristics of the mother giving spontaneous vaginal birth. The authors discuss the influence of narcotic analgesics, neuroaxial analgesia and inhalation analgesia on perinatal and obstetric outcomes, duration of labor and delivery, rates of surgical delivery, with assessment of their side effects, patient's satisfaction with the quality of analgesia, as well as fetal status at birth, neurological status and umbilical blood gases. The use of narcotic analgesics is associated with the risks of inadequate analgesia and such adverse reactions as nausea, vomiting, dizziness in the mother and respiratory suppression in the newborn. Regional analgesia with highly concentrated analgesic solution is associated with pelvic muscle relaxation that may result in the fetus malposition and an increase in duration of delivery. Inhalation of nitrogen monoxide for labor analgesia is no longer used due to its low effectiveness and frequent side effects. The analysis of few publications on the use of inhalation anesthesia with flurane derivatives shows an absence of papers with detailed description of its safety, maternal and fetal effects of an inhalational anesthetic and its influence on perinatal and obstetric outcomes. Thus, the apparent well-doing of the methods used for labor analgesia and anesthesia is rather relative, and we believe that many issues of anesthesiological management have not been unequivocally resolved from the perspective of their effects on the mother, fetus and the newborn.

Almanac of Clinical Medicine. 2018;46(2):137-145
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Cavernous malformations in children: a review of the literature

Popov V.E., Livshits M.I., Bashlachev M.G., Nalivkin A.E.


Cavernous malformation (CM) is a rare vascular disorder of the brain in children. Its prevalence in the general population is in the range of 0.1 to 0.9%, with about one quarter of cases occurring in children. This descriptive review presents an analysis of 17 publications in English and Russian literature on the series of children with cavernomas of the central nervous system and describes their etiology, pathophysiology, clinical particulars, and methods of diagnosis, management, prognosis and outcomes in pediatric practice. In most of the published studies, surgery was performed for 35.3 to 100% of the CM diagnosed during a hemorrhage. The indications for surgical management of CM have been poorly described, and this issue remains unresolved so far. There is also no consensus on the treatment strategy for deeply located cavernomas (brainstem, thalamus and basal ganglia), asymptomatic supratentorial cavernomas and CM located in the functionally important zones of the cortex. Criteria for determination of the intervention volume in patients with CM and symptomatic epilepsy have not been determined, as well. All these issues require further evaluation in multicenter randomized trials.

Almanac of Clinical Medicine. 2018;46(2):146-159
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Tetanus in children: current concepts of the infection management

Petlakh V.I.


The review presents current data on epidemiology, prophylaxis and treatment of tetanus in children. The highest rates of morbidity and mortality, primarily those for neonatal tetanus, are seen in the warm climatic zone countries with a low level of medical care. According to World Health Organization estimates, in 2013, neonatal tetanus killed about 49,000 newborns. Due to active immunization in Russia, only isolated cases of tetanus do occur. However, due to rare incidence and absence of causal treatment, its diagnosis and management can be challenging. The article focuses on the surgical management of wounds as an important element of non-specific disease prevention. The concept of active surgical strategy is proposed in tetanus, based on a one-stage radical excision of infected tissues, up to the amputation of the limb if vitally indicated. The effectiveness of treatment of tetanus patients depends on a combination of several conditions, such as the presence of highly skilled experienced personnel in a specialized multidisciplinary center, modern equipment and medical preparations, as well as rational use of specific therapy.

Almanac of Clinical Medicine. 2018;46(2):160-170
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Invasive streptococcal group A infection in children: а review of the literature and a clinical case of the toxic shock syndrome and complicated community-acquired pneumonia in a child with lung malformation

Meskina E.R., Khadisova M.K.


Streptococcal group A  infection (SGAI) remains an important cause of morbidity and mortality in children. In the recent years, the spread of new highly virulent strains of Streptococcus pyogenes, capable of producing cytolysins and pyrogenic exotoxins (superantigens) has led to an increase in the number of severe forms of diseases with high mortality rates. Invasive infection can occur as necrotizing fasciitis, myositis, sepsis, toxic shock syndrome, scarlet fever, meningitis, myocarditis, and pneumonia. A variety of symptoms in patients with tonsillitis without purulent depositions or after a blunt trauma of soft tissues, such as vomiting, diarrhea, and abdominal pain, can mimic other diseases. The toxic shock syndrome with circulatory collapse, hypotension, acute renal failure, and coagulopathy may develop rapidly and be fatal if not recognized on time or if treated inadequately. Time-sensitive combined antimicrobial therapy and adequate fluid administration, before the bacteriological results are obtained, are important components of any successful treatment. The review describes the current epidemiological situation, diagnostic criteria and treatment strategies for invasive SGAI with an emphasis on the toxic shock syndrome. We present our own observation of SGAI in a 5-year-old child with tonsillitis without purulent depositions, with abdominal pain, typical erythematous rash with desquamation at typical time intervals, and a toxic shock syndrome and pneumonia complicated by pleuritis and pneumohydorotorax. The complications and duration of pneumonia were related to lung malformation (adenomatous cystic type 1 malformation of the lungs), which was newly detected at the time of the disease.

Conclusion: Due to global spread of SGAI, doctors should be alert to its severe manifestations.

Almanac of Clinical Medicine. 2018;46(2):171-183
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The PFAPA syndrome: current paradigm and a clinical case description

Kuznetsova M.A., Zryachkin N.I., Tsareva Y.A., Elizarova T.V., Zakharova G.R.


In the last decades, hereditary autoinflammatory diseases / syndromes (HAIDS) are in the focus of research and practical interests of clinicians. Common characteristics of all known HAIDS include periodic fever and systemic inflammation in combination with other clinical syndromes of certain persistence. According to current understanding, HAIDS are considered the primary immunodeficiency states, related to genetic disruption of the interplay between inflammation regulators that arise in the absence of any pathogen. Many HAIDS manifesting at childhood are associated with severe natural course and serious prognosis. An exception from this is one of the most prevalent HAIDS in children, the PFAPA syndrome, which has a favorable outcome. The term “PFAPA syndrome” is an acronym of the main clinical manifestations, such as Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis. Given the early age of its manifestation, coinciding with the time of a child's socialization, PFAPA patients can be mistakenly follow-up within the group of “frequently sick children” for many years, with high medication load. The disease is triggered by genetically determined dysregulation of congenital immunity associated with excessive production of inflammation mediators (IL-1, TNFα, IL-6, IL-12p70, etc.), with no signs of autoimmunity (autoantibodies, autoreactive T-lymphocytes). There are no specific biological markers for the PFAPA syndrome, therefore, the diagnosis is largely based on the knowledge of the main clinical symptoms of the disease, described in detail by G.S. Marshall (1987), and on the high efficacy of glucocorticosteroids. The authors present a clinical case of a 4 year and 3 month's child who suffered from repeated attacks of PFAPA-syndrome from the age of 1.5 years that recurred at a constant rate every 1.5 to 2 months. Initially, all PFAPA episodes were interpreted as manifestations of a complicated acute respiratory viral infection. Conventional therapy was ineffective. Medical examination of the parents showed chronic tonsillitis in the mother; her subsequent tonsillectomy had no effect on the course of the disease in the child. Only by the age of four, the diagnosis of the Marshall syndrome was first suspected and then confirmed. With a diagnostic and therapeutic purpose, prednisolone was administered at a dose of 1.5 mg/kg body weight with prompt normalization of the body temperature and improvement of the patients' general condition. Assessment performed at 6 months after this confirmed the adequacy of the treatment strategy, while the frequency of PFAPA episodes reduced and they became mild.

Conclusion: It is necessary to increase doctors' awareness of HAIDS and of PFAPA syndrome in particular, that would ensure timely diagnosis and proper treatment.

Almanac of Clinical Medicine. 2018;46(2):184-193
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Age-related changes in production of short-chain fatty acids by gut microbiome in patients without gastroenterological diseases

Zatevalov A.M., Selkova E.P., Gudova N.V., Oganesyan A.S.


Rationale: Multiple biological effects of short chain fatty acids (SCFA) and the possibility to modify their composition by probiotics and prebiotics is in the focus of attention of researchers and clinicians. However, big studies with assessment of the whole spectrum of SCFA produced by gut microbiome and calculated indexes of their relative content are lacking.

Aim: To determine concentrations and ratios of fecal SCFA (functional activity of the gut microbiome) depending on the age of patients without gastrointestinal disorders.

Materials and methods: SCFA fecal concentrations were measured by gas liquid chromatography in 6836 patients aged from 1 month to 85 years without any functional or chronic gastrointestinal pathology, infectious diseases and/or obesity. The time periods with homogenous values of the parameters were determined by identification of constant trends of their means (medians) with 1-month accuracy in children below 5 years of age and with 1-year accuracy in the patients above 1 years of age. The results obtained for the chosen time intervals were compared with Mann-Whitney's test at 95% significance level (p < 0.05).

Results: We performed descriptive statistics for absolute and relative content of SCFA and their structural indexes. It was shown that the parameters characterizing functional activity of gut microbiome have different critical stages in their age-related changes. For each parameter, 2 or 3 stages of changes were identified that occurred at early age, mainly before the age of two. The final SCFA structure was stable by 2 years and 5 months of age. Total SCFA levels reached those typical for adults by the age of 12. The structural index was most sensitive to integrated changes of the microbiome structure.

Conclusion: Age-related characteristics of gut microbiome should be taken into account when performing clinical studies on effectiveness of therapeutic interventions and assessing the parameters in a given patient.

Almanac of Clinical Medicine. 2018;46(2):109-117
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Effectiveness of the probiotic B. bifidum 1 for the prevention of recurrent respiratory infections in children of 7–11 years old with functional and chronic disorders of gastrointestinal tract

Meskina E.R., Medvedeva E.A., Feklisova L.V.


Background: Acute respiratory infections (ARI) are a significant public health problem worldwide due to their high incidence and lack of specific prevention for most of them. Previous systematic reviews have demonstrated the possibility to use probiotics to prevent ARI in children. The prophylactic efficacy of the B. bifidum 1 strain in patients with recurrent ARI has not been investigated specifically against the background of concomitant gastrointestinal disorders, which may affect the effectiveness of probiotic therapy.

Aim: To evaluate the effectiveness and safety of the sorbed probiotic B. bifidum 1 for prevention of ARI in children of 7 to 11 years of age with functional intestinal disorders or gastritis / gastroduodenitis.

Materials and methods: This prospective, randomized, open-label study was completed by 44 children divided into two parallel groups: with and without administration of the sorbed B. bifidum 1 at 5 × 107 CFU three times daily for 21 days as a component of a comprehensive sanatorium treatment for recurrent ARI. The children were followed up for three months after the end of the treatment in a winter season, with assessment of frequency, severity and duration of ARI episodes.

Results: The use of B. bifidum 1 in children of 7–11 years old with functional and chronic gastrointestinal disorders reduced the incidence of upper respiratory tract infections (relative risk reduction 0.48, 95% confidence interval 0.15–0.68) and mean duration of respiratory diseases by 2.26 days (95% confidence interval 0.23–4.27). It also reduced fever, frequency of cases with cough and the need in antibiotic therapy. The efficacy was related mainly to a decrease in the number of children with more than one ARI episode during the three months of the winter season.

Conclusion: The results of probiotics use should be evaluated with consideration of underlying disease, which can more clearly indicate the size of their effect. The use of probiotics for prevention of infectious diseases, including respiratory infections, in children with functional and chronic gastrointestinal disorders can be promising in reduction of the overall morbidity and requires further studies.

Almanac of Clinical Medicine. 2018;46(2):118-125
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Clinical and anamnestic criteria for early diagnosis of herpetic eczema in children with atopic dermatitis

Stadnikova A.S., Tamrazova O.B., Chebotareva T.A.


Rationale: Herpetic eczema (HE), being one of manifestations of generalized Herpes simplex virus (HSV) infection, presents mostly as a complication of atopic dermatitis (AD). This is a potentially life-threatening infection with mortality rates of up to 9%. Early diagnosis and timely beginning of antiviral treatment may help to avoid severe complications and mortality in children with HE.

Aim: To evaluate factors predisposing to the development of HE in children with AD and to identify a high risk group.

Materials and methods: One hundred and fifty (150) children with AD aged from 4 months to 18 years were recruited into this one-center prospective stratified observational study. The main group included 113 children with HE with underlying AD, while the comparison group comprised 37  children with AD exacerbations without HE. HSV infection was confirmed by determination of the viral DNA in blood by polymerase chain reaction. The severity of AD at study entry and during follow up was assessed with SCORAD scale.

Results: All children with HE + AD (100%) had been in contact with individuals with clinical manifestations of HSV infection (35.1% in the comparison group, p < 0.001). The main predictors of HE in AD patients were as follows: age below 1 year (relative risk increase (RRI) 2.86, 95% confidence interval (CI) -7.91 / -0.68, p < 0.001), autumn and winter season (RRI 1.68, 95% CI -5.3 / -0.15, p = 0.018), moderate and severe AD (RRI 0.91, 95% CI -2.11 / -0.17, p < 0.002).

Conclusion: A combination of 3 risk factors, such as age below 1 year, autumn and winter season, moderate and severe AD, puts a patient into a high risk of HE. Children from the risk group should be isolated from patients with manifest HSV infection.

Almanac of Clinical Medicine. 2018;46(2):126-131
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Effectiveness of brachytherapy in the combination treatment of retinoblastoma

Saakyan S.V., Valskiy V.V.


Background: Retinoblastoma is a malignant tumor of the eye retina that occurs mostly in children. In the absence of treatment, the disease leads not only to vision loss, but also to death of the child. At present, combined organ-preserving methods of treatment are preferred. These include polychemotherapy and a local intervention on the tumor, the "golden standard" of which being brachytherapy.

Aim: To study the effectiveness of brachytherapy against the background polychemotherapy.

Materials and methods: We analyzed retrospectively medical files of 104 children with retinoblastoma aged from 5 months to 5 years (mean age 21  months), who underwent brachytherapy as a local component of management from 2010 to 2015 in the Moscow Helmholtz Research Institute of Eye Diseases. Multifocal lesions were identified in 43 cases and bilateral tumors in 87 children. In 33 cases, the worst eye was removed. Endophytic and mixed forms of tumors growth were most prevalent. Before the brachytherapy, all children received polychemotherapy (2 to 3 courses). The average tumor thickness was 2.74 mm (from 1 to 6.4 mm); its mean maximal transverse dimension was 6.27 mm. Indigenous ophthalmic applicators with isotopes 90Sr + 90Y and 106Ru + 106Rh were used. The average dose on the tumor apex with the strontium applicator was 142.1 (120–170) Gy, with ruthenic one, 107.4 (69–168) Gy; the scleral doses were 751.3 и 504.4 Gy, respectively. The median follow-up was 51 months. The patients were assessed every 3 to 4 months with ophthalmoscopy and ultrasound examination. The following effectiveness criteria were used: complete resorption, the tumor cannot be identified; partial resorption, a decrease in the initial tumor size by at least 50%; no effect, a decrease in the initial tumor size by less than 50% or an increase in the size of the tumor.

Results: Complete resorption of the tumor occurred in 60.6% (n = 63) of the patients at 3 months and in additional 24% (n = 25) at 6 months. During the first year after the radiation, complete resorption of retinoblastoma was achieved 93.3% (n = 97) of the children. All children are alive, no distant metastases have been found. Early complications after brachytherapy were noted in 3  children: hemophthalmia, in 1, retinal detachment, in 1, hemophthalmia with retinal detachment, in  1, when the radiation dose on the sclera exceeded 1000  Gy. Continued tumor growth or relapses were detected in 7 (6.7%) patients. The reason to enucleate two eyes was the tumor invasion into the orbit (1.9%). Visual functions are preserved in 85 (81.7%) children, with a high visual acuity (0.9–1.0) in 21 children, and 0.1–0.8 in 21 children, as well.

Conclusion: Brachytherapy is a highly effective method of local destruction of retinoblastoma, which, in the vast majority of cases, allows for complete resorption of the irradiated tumor and for maintenance of high visual acuity in almost half of patients.

Almanac of Clinical Medicine. 2018;46(2):132-136
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Intensive care of children who require interhospital transport (a clinical guideline draft)

Shmakov A.N., Aleksandrovich Y.S., Pshenisnov K.V., Zabolotskiy D.V., Razumov S.A.


The article presents a draft of clinical guidelines for intensive care of children, who require interhospital transport; it was elaborated with consideration of territorial characteristics of the Russian Federation. Legal aspects of organization of interhospital transport service and possible side effects of transportation are considered in detail. General description and the main advantages and disadvantages of the air transport and ground ambulance transport are presented. A system for transport risk assessment is proposed, based on ranks that correspond to the duration of safe transport time. Original scales to assess the transportation risk based on the necessity of emergency rehydration, inotropic, vasopressor and respiratory support are presented. Special attention is focused on the preparation of critically ill children to interhospital transport, with detailed protocol for intensive care, monitoring and caring activities while transporting. The goal parameters for patient stabilization in the next six hours after transport are described. The use of proposed key principles of safe transport would significantly improve the quality of medical care for children, who require transportation to specialized units.

Almanac of Clinical Medicine. 2018;46(2):94-108
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Experience of medical treatment of neonates with Ebstein anomaly in the intensive care unit

Tarayan M.V., Shkarina N.V., Efremov E.S.


Background: Neonates with Ebstein anomaly may remain a  challenge for neonatal intensive care units due to continuously changing clinical manifestations. Maintaining an adequate cardiac output in the presence of cardiomegaly, severe cyanosis, high pulmonary vascular resistance, and rhythm disorders is a difficult task.

Aim: To demonstrate the possibility of conservative management, as well as clinical and instrumental criteria of assessment of neonates with Ebstein anomaly and arterial hypoxemia and cardiomegaly.

Materials and methods: Four neonates aged from 3 to 8 days of life were admitted to the neonate intensive care unit due to persistent arterial hypoxemia (SaO2 ≤ 90%) and O2-dependence. Their cardiothoracic ratios ranged from 55 to 75% and were higher in the neonate with initial severe tricuspidal insufficiency (stage 3–4). Great Ormond Street Echocardiography (GOSE) score > 1 was found in 2 neonates with clinical manifestation of severe heart failure, arterial hypoxemia and cardiomegaly.

Results: During the following 3 to 4 days, two neonates (aged 5 and 6 days) were transferred to the 2nd stage of care due to the absence of clinical manifestations of heart failure and severe hypoxemia. In the other two cases, intensive management was necessary, with catecholamine support, oxygen therapy, infusion of prostaglandin E1, anti-arrhythmic agents, with no surgical intervention.

Conclusion: The majority of symptomatic neonates with Ebstein anomaly can be stabilized in the settings of adequate conservative management. However, some of them would require transition from conservative treatment to surgical intervention. Such clinical and instrumental criteria, as SaO2, cardiothoracic ratio, and GOSE are the main benchmarks to choose between conservative and surgical strategy.

Almanac of Clinical Medicine. 2018;46(2):194-199
pages 194-199 views

A case of familial neurofibromatosis in pediatric practice

Zryachkin N.I., Buchkova T.N., Chebotareva G.I., Styazhkina N.B.


The article describes a  clinical case of familial neurofibromatosis. Neurofibromatosis type  1 was diagnosed in a 9-year old patient according to diagnostic criteria by the International Expert Committee on Neurofibromatosis, based on two criteria: 2 or more neurofibromas and neurofibromatosis type 1 and type 2 in the first-degree relatives. The particulars of the clinical case include the absence of any skin manifestations and an unfavorable prognosis. High awareness of this disorder among primary care physicians, including pediatricians, generalists and family doctors, neurologists, dermatologists, ophthalmologists and surgeons, is necessary for early clinical identification of neurofibromatosis type  1 patients and their regular clinical monitoring, continuity of management and implementation of adequate measures of primary and secondary prevention of its complications.

Almanac of Clinical Medicine. 2018;46(2):200-205
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A rare case of a duodenocolic fistula in a 3-year old child

Bokova T.A., Mashkov A.E., Lukina E.V., Slesarev V.V.


Intraintestinal fistula is an unnatural communication between the intestinal cavity and other parts of the gut. Duodenocolic fistulas are common in adult patients with duodenal peptic ulcer or colon malignancies. In children, the formation of intraintestinal fistulas is possible as a rare complication of necrotizing enterocolitis of the newborn, after swallowing of several (two and more) magnetic foreign bodies localized in different parts of the digestive tract, as well as a complication of Crohn's disease at an older age. The article presents a clinical case of a duodenocolic fistula in a 3-year-old child. The patient Sh., 3 years and 2 months old, was admitted to the Pediatric Department of our clinic with a malabsorption syndrome and complaints of periodic vomiting after meals, weakness, tiredness, unstable light grayish stools, flatulence, periodic abdominal pains, and weight loss. There were clinical signs of stage II hypotrophy, protein and energy insufficiency. Laboratory tests showed low protein, albumin, and cholesterol levels, hypochromic anemia; fecal steatorrhea, creatorrhea, and amilorrhea. The differential diagnosis included intestinal malabsorption syndrome, presumably of a secondary origin, intestinal infection, congenital pancreatic disease, hereditary metabolic disorders, cystic fibrosis, celiac disease, lambliosis, and tumor. Multiple endoscopic and radiological examinations of the gastrointestinal tract were performed, but the intraintestinal fistula was identified only after repeated examinations. The patient's medical history from the first referral to the final diagnosis lasted about 9 months. The mechanism of the fistula formation in this patient is unclear. The clinical manifestation corresponded to the location of the fistula. In the long-term, the functioning of pathological intraintestinal communication could have a negative impact on the growth and development of the child; mucosal atrophy of the descending part of the intestine would have been possible, with progressive cachexy that could have become fatal.

Almanac of Clinical Medicine. 2018;46(2):206-210
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