[Association between preoperative cholecalciferol therapy and hypocalcemia after parathyroidectomy in patients with primary hyperparathyroidism].

BACKGROUND: Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors. Parathyroidectomy (PTE) is the main treatment for PHPT, but it can lead to hypocalcemia in up to 46% of cases. Hypocalcemia is associated with seizures and life-threatening cardiac arrhythmias, and vitamin D deficiency can exacerbate PHPT severity and contribute to «hungry bones syndrome,¼ resulting in severe and persistent postoperative hypocalcemia. AIM: To evaluate the association and determine the strength of the relationship between preoperative cholecalciferol therapy and the occurrence of hypocalcemia within 1-3 days after PTE in patients with PHPT. MATERIALS AND METHODS: The study was conducted at the Endocrinology Research Centre, during the periods of 1993-2010 and 2017-2020. The inclusion criteria consisted of patients diagnosed with PHPT who required PTE, had a serum 25-hydroxyvitamin D (25(OH)D) level below 20 ng/mL, and a serum total calcium level below 3 mmol/L. The exclusion criterion was the use of medications that affect calcium-phosphorus metabolism, including cinacalcet, denosumab, or bisphosphonates, either as monotherapy or as part of combination therapy. RESULTS: There were 117 patients, including 110 (94%) females and 7 (6%) males. The median age and interquartile range were 58 [49; 65] years. Among the participants, 21 (18%) received cholecalciferol supplementation for a duration of 2 weeks to 2 months prior to PTE, aiming to address vitamin D deficiency. The remaining 96 (82%) participants did not receive -cholecalciferol supplementation. Both groups, i.e., participants receiving cholecalciferol and those who did not, were similar in terms of anthropometric factors (sex and age at the time of surgery), preoperative clinical characteristics (BMD decrease), and laboratory parameters (PTH, total calcium, phosphorus, ALP, OC, CTX-1, and 25(OH)D levels). The occurrence of postoperative hypocalcemia was significantly lower in participants who received cholecalciferol supplementation (10% vs. 63%, p<0,001, FET2). Cholecalciferol intake showed a negative association with hypocalcemia development (RR=0,15, 95% CI (0,03; 0,51)). CONCLUSION: Preoperative cholecalciferol supplementation for 2 weeks to 2 months before PTE reduces the risk of postoperative hypocalcemia in patients with PHPT by 2-33 times.

Sample Size Calculation for Clinical Trials of Medical Decision Support Systems with Binary Outcome.

Currently, software products for use in medicine are actively developed. Among them, the dominant share belongs to clinical decision support systems (CDSS), which can be intelligent (based on mathematical models obtained by machine learning methods or other artificial intelligence technologies) or non-intelligent. For the state registration of CDSSs as software medical products, clinical trials are required, and the protocol of trial is developed jointly by the developer and an authorized medical organization. One of the mandatory components of the protocol is the calculation of the sample size. This article discusses the calculation of the sample size for the most common case, the binary outcome in diagnostic/screening and predictive systems. For diagnostic/screening models, cases of a non-comparative study, comparative study with testing of the superiority hypothesis, comparative study with testing of a hypothesis of non-inferiority in cross-sectional studies are considered. For predictive models, cases of randomized controlled trials of the complex intervention "prediction + prediction-dependent patient management" with testing of the hypothesis of superiority and non-inferiority are considered. It is emphasized that representativeness of the sample and other design components are no less important in clinical trials than sample size. They are even more important since systematic biases in clinical trials are primary, and even the most sophisticated statistical analysis cannot compensate for design defects. The reduction of clinical trials to external validation of models (i.e. evaluation of accuracy metrics on external data) seems completely unreasonable. It is recommended to perform clinical trials with the design adequate to the tasks, so that further clinical and economic analysis and comprehensive assessment of medical technologies are possible. The sample size calculation methods described in the article can potentially be applied to a wider range of medical devices.

[The prospects for the creation of the National Center for Personalized Medicine of Endocrine Diseases].

The National Medical Research Center for Endocrinology (NMRCE) received the right to implement the development program of the World-class Research Centre "The National Center for personalized medicine of endocrine diseases" (NMCPMED). The objective of the NMCPMED will be not only the creation of a system of personalized treatment, but also the training of new specialists for medicine.  Fundamental researches, carried out on the basis of the already existing institutes and laboratories of the NMRCE will be expanded by creating new laboratories of the NCPMED created de novo in accordance with the approved project. This article introduces the reader to the most important laboratories that would be created in NCPMED. These are laboratories of general, molecular and population genetics, bioinformatics, pharmacogenomics, microbiota, genome editing, mathematical and digital technologies, non-invasive technologies for the diagnosis of endocrinopathies, cellular technologies, artificial intelligence and a fundamentally new laboratory of metabolic visualization and radioteranostics. The authors hope that readers of one of the main journals for endocrinologists in our country will actively participate in the  implementation of NMRCE, as both young and experienced talented researchers will have a chance to be a part of the Centre. To realize the ambitious implementation plans for the achievements of the Centre, it is necessary to radically change the worldview of the doctors in our country, to train them in a new way, and to expand the structure of the Center's team by increasing the number of specialists in medical genetics, transcriptomics, biostatistics and bioinformatics, working at the intersection of experimental and clinical endocrinology, and ensuring the transit of innovative technologies into clinical practice. New laboratories of the World-Class Research Center, will become the place of routine work of a new generation of doctors, who possess not only the basics of clinical work, but also the skills of fundamental researches that will allow them to significantly improve the methods of diagnosis and treatment.

Towards Good Statistical Practice. CORSTAN Validated Questionnaire for Assessing the Correctness of Statistical Analysis in Medical Research.

BACKGROUND: In evidence-based medicine, the research methodology is determined by the risks of systematic biases and incorrect data analysis. Minimizing both risks increases the internal validity of the study. There are numerous recommendations and guidelines for data analysis and reporting, but the international community has not yet developed a questionnaire for reviewers to assess the quality of statistical analysis. AIM: To develop a tool for formalized assessment of the quality of statistical analysis presented in scientific medical publications. MATERIALS AND METHODS: The questionnaire was developed based on the authors' decades of experience in statistical data analysis and reviewing the statistical aspects of biomedical articles and dissertations. The SAMPL guidelines, ICH E9, and other guidelines were taken into account when developing the questionnaire. Internal validation of the questionnaire was based on an independent assessment by two experts of 20 randomly selected articles on randomized controlled trials (RCTs) from elibrary.ru, and further statistical analysis of the agreement of experts' conclusions. RESULTS: The CORSTAN (CORrect STatistical ANalysis) questionnaire was developed, which consists of two parts: the first part (10 questions) is intended for evaluating studies of any designs, while the second (following eight questions) is for additional assessment of RCTs. A stratification of the risk of incorrect statistical analysis is proposed. The evaluation of the questionnaire's internal validity showed its substantial and almost perfect agreement for each question and each article both in the sum of points and risk level. CONCLUSION: The use of the questionnaire will simplify and harmonize the statistical review of publications and manuscripts in various institutions - scientific journals, dissertation boards, etc. The questionnaire can also be helpful for authors during preparing manuscripts; it will also help improve the quality of publications and research itself. We plan to improve the questionnaire as we gain experience in its application.

[The effect of various multimodal analgesia regimens during surgical treatment of patients with spinal stenosis on the rate of failed back surgery syndrome]. / Vliianie razlichnykh mul'timodal'nykh skhem analgezii pri khirurgicheskom lechenii patsientov so stenozom pozvonochnogo kanala na chastotu sindroma neudachnoi operatsii na pozvonochnike.

OBJECTIVE: To determine the effect of various methods of perioperative analgesia on the rate of failed back surgery syndrome in patients operated on for spinal stenosis. MATERIAL AND METHODS: A total of 122 patients were operated on for spinal stenosis in 2010-2016. The patients were assigned to groups according to the type of received analgesia: Group K (n=19) underwent analgesia on-demand. Patients in the PMA group (n=21) received preventive multimodal analgesia (PMA) with ketoprofen, paracetamol and morphine. Patients in the PMA+PG (n=20) and PMA+N (n=20) groups additionally received pregabalin and nefopam, respectively. Patients in the PMA+E group (n=22) received continuous epidural analgesia with a combination of ropivacaine and morphine. In patients in the PMA+I group (n=20), the wound was infiltrated with ropivacaine and ketorolac. RESULTS AND CONCLUSION: In Group K, analgesia was not adequate during five postoperative days. Analgesia with PMA resulted in significant pain reduction during three postoperative days compared to Group K. Wound infiltration in addition to PMA was followed by more significant pain relief during six postoperative hours (compared to the PMA group). Administration of pregabalin or nefopam, as well as epidural analgesia, did not improve quality of postoperative analgesia. Five to seven months after the surgery, 66% (57; 75%) of patients had low back and/or leg pain; 41% (32; 50%) of patients had leg pain. Among patients suffering from pain, 32-41% patients had the severe chronic pain syndrome that resulted in sleep disorder, disability and significant deterioration of quality of life. The rate of failed back surgery syndrome did not depend on the perioperative analgesia regimen.

[Prognostic models of the severity of acute dynamic pain on the first postoperative day and the likelihood of chronic postoperative pain in spine surgery]. / Prognosticheskie modeli vyrazhennosti ostroi dinamicheskoi boli v pervye sutki posle operatsii i veroiatnosti vozniknoveniia khronicheskoi posleoperatsionnoi boli v khirurgii pozvonochnika.

The risk factors for acute pain as well as chronic pain syndrome (CPS) in spine surgery have not been defined to date. PURPOSE: To define the prognostic parameters of acute pain severity and the risk of CPS in patients operated on for spinal diseases and injuries. MATERIAL AND METHODS: The study included 291 patients operated on for degenerative diseases and injuries of the spine at the Sklifosovsky Research Institute of Emergency Medicine in 2010-2016. Sociodemographic and clinical data and the psychological status of patients were evaluated. A mechanical algometer was used to measure the pain threshold (PT) and pain tolerance. The movement pain intensity was assessed by using a visual analog scale (VAS) on the day of surgery. Pain was considered minor at a median score of 0-4 cm and severe at a median score of 5-10 cm. The presence of CPS was assessed during a telephone survey 5-7 months after surgery. RESULTS: The gender, PT, dynamic pain intensity before surgery, and expectation of postoperative pain are risk factors for severe acute postoperative pain. A multinomial logit regression model (Hosmer-Lemeshow test - 4.322; p=0.827) predicts minor dynamic pain on the 1st postoperative day with an accuracy of 70% (95% CI 63-76). The age and dynamic pain intensity on the 1st postoperative are the risk factors for CPS; the multinomial logit regression model (Hosmer-Lemeshow test - 3.1; p=0.928) predicts CPS with an accuracy of 65% (95% CI 59-71) 5-7 months after surgery. CONCLUSION: The developed software in the form of MS Excel calculators provides a particular patient with preoperative assessment of the risk for minor acute dynamic pain on the 1st postoperative day and CPS 5-7 months after surgery.

[THE CHOICE OF PERIOPERATIVE MULTIMODAL ANALGESIA IN PATIENTS WITH LUMBAR HERNIATED DISC: THE PRELIMINARY RESULTS.]

DESIGN: 129 patients scheduled for elective lumbar discectomy in 2010-2013 were enrolled in prospective study. Group K (n=20) underwent general anaesthesia and postoperative analgesia on-demand. Group PMA+SA (n=23) got subarachnoid block and preventive multimodal analgesia (PMA) including ketoprofen, paracetamol and nalbuphine. At PMA group (n=21) general anaesthesia and PMA were used; at PMA+I (n=21) also bupivacaine wound infiltration was administrated; at PlvL4+S (n=20) - depo-corticosteroid was applied locally on affected spinal nerve root; at PMA+IS (n=24) wound infiltration and local corticosteroids were combined. Patients could use i.v. nalbuphine on-demand by PCA device in addition to PMA post-operatively. 7 days post-operatively, the pain scores using 10 cm VAS at rest and during movement were also recorded. RESULTS: Group K patients had not adequate pain relief during 4 postoperative days. At PMA group the postoperative analgesia was adequate during the whole assessment time, PMA group patients had significant less pain scores than at K group during 4 postoperative days. Patients at PM +SA had better than PMA group pain relief only during 2 hours postoperatively. Groups PMA+I and PMA+IS did not demand nalbuphine at al. Their pain scores were signifcant less than at PMA group during 2 postoperative days. CONCLUSIONS: Postoperative analgesia on-demand is not adequate but the PMA is. Subarachnoid block results in decreasing severity of pain only during first hours postoperatively. The additional bupivacaine wound infiltration in pa- tients with lumbar herniated disc follows avoiding of opioids and significant pain relief during 2 postoperative days.

[Assessment of pain relief in patients receiving different variants of multimodal analgesia after major gynecological surgery].

The major gynecology surgery generally results in severe postoperative pain. Currently multimodal analgesia concept is widely used for the aim of postoperative pain relief optimization. According to this theory it is worth using the medication with different mechanism in order to increase analgesia qualify, decrease analgesic consumption and avoid adverse reaction. Unfortunately the surveys recently conducted have been pointed out the postoperative analgesia quality is still insufficient despite of using the concept mentioned above. One way to solve the problem is appearing in daily practice nefopam--centrally acting non-opioid analgesic that inhibits reuptake of serotonin, norepinephrine, and dopamine and also mitigates glutamatergic neurotransmission. In this trial we tried to assess the postoperative daily used analgesia quality and potency of preemptive multimodal analgesia model consisted of nefopam, ketoprofen, paracetamol and morphine.

Pathophysiological aspects of the formation of neurological deficit in multiple sclerosis.

The results of complex studies were used to formulate a concept of the development of neurological impairments in multiple sclerosis (MS). Acutely developing impairments to spike propagation, reaching the level of conduction blockade, due to the active pathological process with demyelinating and axonal damage to the CNS lead to the formation of neurological impairments in exacerbations of MS, while complete or partial reversion (regression) of these symptoms in the stage of remission results from compensatory changes in the nature of conduction, which were not, however, accompanied by recovery of electrophysiological measures. The development of stable neurological deficit in secondary-progressive MS is determined by impairments to spike conduction processes associated with significant levels of demyelination and atrophic changes in the CNS, with myelin loss and axon death. Finally, the severity of cognitive changes is determined by differences in the severities of both the focal demyelinating process and diffuse damage to brain substance in MS, including the neurodegenerative component. The main factor in transient increases in symptoms is the universal lability of electrophysiological parameters, including those developing on the background of ion and neurotransmitter imbalance.