Recurrent Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1 Syndrome.

Primary hyperparathyroidism is a common endocrinopathy. Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare autosomal dominantly inherited endocrine tumor predisposition syndrome, with one of main manifestations being primary hyperparathyroidism. We retrospectively evaluated a set of 1011 patients who underwent surgery for primary hyperparathyroidism between the years 2018-2022, and found 78 (8 %) patients who underwent reoperations and 27 patients with MEN1 syndrome. In the group of patients with MEN1 syndrome, 7 (35 %) needed reoperations. Patients with multiple endocrine neoplasia syndrome have a higher risk of needing reoperation. Genetic testing can help identify MEN1 syndrome preoperatively and to better evaluate the approach to surgery.

Molecular Genetic Aspects of Sporadic Multiglandular Primary Hyperparathyroidism.

Multiglandular primary hyperparathyroidism (MGD) represents a rare form of primary hyperparathyroidism (PHPT). MGD is associated with hereditary PHPT, but the sporadic MGD is more common and affects a similar patient profile as single gland parathyroid disease (SGD). The distinction between SGD and MGD is of great clinical importance, especially for the strategy of parathyroidectomy. Based on the limited knowledge available, MGD is likely to be a genetically heterogeneous disease resulting from the interaction of germline and somatic DNA mutations together with epigenetic alterations. Furthermore, these events may combine and occur independently in parathyroid tumors within the same individual with MGD. Gene expression profiling has shown that SGD and MGD may represent distinct entities in parathyroid tumorigenesis. We are waiting for studies to analyze exactly which genes are different in SGD and MGD in order to identify potential biomarkers that can distinguish between the two forms of the disease.

Age-Related Changes in Proinsulin Processing in Normoglycemic Individuals.

In order to understand the pathological changes associated with glucose homeostasis in old age, it is necessary to know the natural changes in the processing of proinsulin to mature insulin. While there is abundant information about insulin production and function in diabetics, the situation in healthy adults and the elderly has surprisingly rarely been investigated. The aim of the study was to determine how proinsulin secretion changes in individuals with normal glucose tolerance during the process of natural aging. A total of 761 individuals (539 women, 222 men) aged 18-90 years with normal fasting glycemia (less than 5.6 mmol/l) were divided into five groups according to age. Body composition and levels of fasting blood glucose, proinsulin, insulin, and C-peptide were determined, and the ratios of proinsulin to both insulin and C-peptide were calculated. The homeostasis model of ?-cell function (HOMA F) and peripheral insulin resistance (HOMA R) were calculated. The effect of age was assessed using an ANOVA model consisting of the factors sex, age, and sex × age interaction. Statgraphics Centurion v. XVIII statistical software was used. Glycemia, insulin, C-peptide and HOMA R increased in both sexes up to 75 years. On the contrary, proinsulin levels as well as proinsulin/insulin and proinsulin/C-peptide ratios decreased with age up to 75 years. In normoglycemic and normotolerant people, both women and men, the aging process is associated with decreased insulin sensitivity compensated by potentiation of insulin production. In older age, there is also a gradual decrease in circulating proinsulin, which can be explained by its more efficient processing into active insulin by matured healthy beta cells.

[Surgical Treatment of Tuberculous Spondylodiscitis]. / Operacní lécba tuberkulózní spondylodiscitidy.

PURPOSE OF THE STUDY The paper presents a monocentric retrospective study of patients treated surgically for spinal tuberculosis. Clinical and radiological results are analysed, early and late complications are recorded. The study aims to answer the following questions. 1. Can we use instrumentation to restore the stability and alignment in the infected spinal focus? 2. Should we always perform radical anterior resection of TBC lesions? 3. What is the prognosis of surgical treatment of TBC patients with neurological deficit manifestation? MATERIAL AND METHODS Between 2010 and 2020, a total of 12 patients were treated for spinal tuberculosis at our department, of whom 9 patients (5 men, 4 women) with the mean age of 47.3 years (range 29 to 83 years) underwent a surgery. A total of three patients were operated on before the final confirmation of the TBC and treatment with antituberculosis medication, four patients in the initial therapy phase and two patients in the continuous phase. Two patients only underwent a non-instrumented decompression surgery followed by external support fixation. In the other seven patients, always with spinal deformity, instrumentation was used (3 cases of isolated posterior decompression, transpedicular fixation, posterior fusion, 4 cases of anteroposterior instrumented reconstruction). In 2 cases a structural bone graft and in 2 cases an expandable titanium cage were used for anterior column reconstruction. RESULTS Of the total number of patients, altogether eight patients were assessed at 1 year after surgery (one 83-year-old patient died from heart failure 4 months after surgery). Of the remaining eight patients, three patients exhibited a neurological deficit and postoperative regression of the finding. The McCormick score improved from the preoperative mean score of 3.25 to 1.62 at 1 year after surgery (p < 0.001). The clinical VAS score regressed from 5.75 to 1.63 at 1 year after surgery (p < 0.001). Radiographic healing of the anterior fusion was achieved in all patients, both after decompression and instrumented surgery. The initial mean kyphosis of 20.36 degrees of the operated segment measured by the mCobb angle was corrected to 14.6 degrees postoperatively, with a subsequent slight deterioration to 14.86 degrees (p < 0.05). The greatest correction was achieved in patients who had undergone a two-stage surgery with anterior resection and AP reconstruction. DISCUSSION In our cohort, titanium instrumentation was used in seven of nine patients. One patient only manifested persistent tuberculosis with nonspecific bacterial flora superinfection. Revision surgery with anterior radical debridement and subsequent treatment with antituberculotic drugs healed the patient. There were four patients with major preoperative neurological deficit persisting more than 2 weeks before the final treatment with subsequent improvement in all cases. These patients were treated with anteroposterior reconstruction and anterior radical debridement. CONCLUSIONS No increased risk of recurrent infection associated with the use of spinal instrumentation was found in the study. Anterior radical debridement is performed in patients with manifested kyphotic deformity and spinal canal compression, followed by reconstruction with a structural bone graft or a titanium cage. The other patients are treated based on the principle of "optimal" debridement with or without the use of transpedicular instrumentation. If adequate spinal canal decompression and stability are achieved, neurological improvement can be anticipated even in case of a major neurological deficit. Key words: spine tuberculosis, tuberculous spondylitis, Pott's disease, anterior debridement, spine instrumentation.

[Modified Harrington Procedure in the Treatment of Extensive Tumor Defects of the Acetabulum]. / Modifikovaná Harringtonova operace v terapii rozsáhlých nádorových defektu acetabula.

PURPOSE OF THE STUDY The increasing prevalance of patients with metastatic bone cancer and their improved survival puts more emphasis on the quality of treatment of bone metastases. Although most pelvic lesions are treated non-operatively, extensive destruction of the acetabular segment poses a therapeutic challenge. A potential treatment option may be the modified Harrington procedure. MATERIAL AND METHODS At our department, this surgical procedure has been opted for in 14 patients (5 men and 9 women) since 2018. The mean age at the time of surgery was 59 years (range 42 to 73). Twelve patients suffered from metastatic cancer, one patient had a fibrosarcoma metastasis and one female patient presented with aggressive pseudotumor. Radiological and clinical followup of the patients was performed. Pain was assessed using the Visual Analogue Scale, and the Harris Hip Score and the MSTS score were used to evaluate the functional outcome. The paired samples Wilcoxon test was used to analyze the statistical significance of the difference. RESULTS The mean follow-up period was 25 months. At the time of assessment, ten patients were alive with the mean follow-up of 29 months (range 2 to 54 months) and four patients had died of cancer progression, with the mean follow-up being 16 months. No perioperative death or mechanical failure were reported. One female patient developed a hematogenous infection during febrile neutropenia, which was successfully managed with early revision and implant preservation. Statistically, a significant improvement in the MSTS (median 23) and HHS (median 86) functional scores compared to the preoperative values (MSTS median 2, p<0.01, r-effect size = 0.6; HHS preop median 0, p<0.005, r-effect size = -0.7) was observed. There was also a statistically significant reduction in pain (VAS postoperative median 1, VAS preoperative median 8, p<0.01, r-effect size = -0.6). All patients were capable of independent ambulation after the surgery, nine patients walked without support. DISCUSSION There are not many alternatives to this surgical procedure. Apart from non-operative palliative treatment, the options include ice cream cone prostheses or customized 3D implants which are, impractical in terms of time and cost. Our results are comparable to other studies, confirming the reproducibility and reliability of the method. CONCLUSIONS The Harrington procedure is an efective method for management of large acetabular tumor defects with good functional outcomes, an acceptable perioperative risk and a low risk of failure in the medium term, thus suitable also for patients with good cancer prognosis. Key words: umor, metastasis, acetabulum, pelvis, Harrington, reconstruction.

[Surgical Treatment of Sacral Chordoma]. / Operacní lécba chordomu sakra.

PURPOSE OF THE STUDY The retrospective study of patients treated for sacral chordoma with respect of complications, clinical outcomes and longterm survival is presented. Three main hypotheses have been formulated. Hypothesis 1: survival of patients with respect to generalization of the disease, manifestation of local recurrence and metastases with a R0 resection margin achieved is longer than survival of patients with a R1 or R2 resection margin. Hypothesis 2: survival of patients with the tumor resected from low endplate of S2 distally is longer than in tumors with resection above this level. Hypothesis 3: resection of large tumors with tumor volume greater than 800 cm³ is associated with a significantly shorter survival than resection of tumors with tumor volume less than 800 cm³. MATERIAL AND METHODS A total of 12 patients (7 women, 5 men), with the mean age of 54.3 years, underwent surgical treatment at our department in 1998-2018. Sacral chordoma proximally achieved S1 level in three cases, S2 level in four cases and S3 level in five cases with volume less than 800 cm³ in eight and greater in four patients. In nine patients sacrectomy using isolated posterior approach was performed and in three patients antero-posterior approach was applied. The Kaplan-Meier survival curve was calculated to estimate the survival of patients. The patients were divided into groups and subsequently compared with respect of achieved radicality of surgical resection, i.e. R0 vs. R1 or R2 resection, secondly of the proximal margin of the tumor/resection, i.e. S1 or S2 vs. S3 distally, and thirdly of the volume of the tumor, i.e. less than 800 cm³ vs. more than 800 cm³. RESULTS At the time of evaluation, a total of seven patients were alive (58.3%), with the mean survival of 9.5 years. One patient died from complications associated with the treatment of obstructive ileus manifested 10 months after primary surgery. The remaining four patients died in relation to the generalization of the disease 14.8 years after primary surgery on average. All the patients, in whom R0 resection was achieved, at the average time of evaluation of 7.3 years (range 2.8-15.8 years) showed no signs of local recurrence or generalization of the disease, whereas in group with R1, R2 resection at the time of evaluation only two patients were still alive, both 16.8 years on average (range 15.2-18.4 years) after surgery with repeatedly treated recurrencies. Frequent postoperative complications were observed in a total of five patients (41.7%). DISCUSSION The study did not confirm any difference in patient's survival with respect of the proximal margin affection of sacrum or tumor size. The decisive factor for survival of patients with sacral chordoma is achieving the R0 resection. The size of the chordoma and proximal achievement increase the complexity of surgery, manifestation of early perioperative and subsequently postoperative complications. CONCLUSIONS In primary surgical treatment of sacral chordoma, we always try to achieve R0 resection. In the case of low-volume tumors from S3 distally, we resect the tumor using the isolated posterior approach. The anterior-posterior approach is preferred in the case of large tumors presenting in the S1/2 region. Key words: sacral chordoma, sacral cancer, wide resection, sacrectomy, vertical rectus abdominus myocutaneous (VRAM) flap.

Multiglandular Parathyroid Disease in Primary Hyperparathyroidism With Inconclusive Conventional Imaging.

Inconclusive preoperative imaging is a strong predictor of multiglandular parathyroid disease (MGD) in patients with primary hyperparathyroidism (PHPT). MGD was investigated in a cohort of 17 patients with PHPT (mean age 64.9 years, total calcium 2.75 mmol/l and parathyroid hormone (PTH) 113.3 ng/l) who underwent 18F-fluorocholine PET/CT (FCH) imaging before surgery. The initial MIBI SPECT scintigraphy (MIBI) and/or neck ultrasound were not conclusive or did not localize all pathological parathyroid glands, and PHPT persisted after surgery. Sporadic MGD was present in 4 of 17 patients with PHPT (24 %). In 3 of 4 patients with MGD, FCH correctly localized 6 pathological parathyroid glands and surgery was successful. Excised parathyroid glands were smaller (p <0.02) and often hyperplastic in MGD than in single gland disease. In two individuals with MGD, excision of a hyperplastic parathyroid gland led to a false positive decline in intraoperative PTH and/or postoperative serum calcium. Although in one patient it was associated with partial false negativity, parathyroid imaging with FCH seemed to be superior to neck ultrasound and/or MIBI scintigraphy in MGD.

[Surgical Treatment of Cervical Spondylodiscitis]. / Operacní lécba krcní spondylodiscitidy.

PURPOSE OF THE STUDY The purpose of the retrospective study is to analyse a group of patients surgically treated for cervical spondylodiscitis. The first hypothesis states that the removal of infected intervertebral disc without its anterior column reconstruction in the acute phase of infection results in worse clinical and radiological evaluation of the patient. The second hypothesis defines that the use of titanium implant in anterior column reconstruction in the chronic phase of infection increases the risk of recurrent infection. MATERIAL AND METHODS The evaluated group of patients who underwent surgery includes a total of 21 patients (8 females, 13 males) with the mean age of 57.6 years. 12 patients in the acute phase of infection were treated by anterior debridement without disc space reconstruction, of whom four patients were completed by posterior instrumented fusion in the second stage. In 9 patients in the chronic phase of infection radical anterior debridement was completed by anterior titanium implant reconstruction, of whom in five patients posterior instrumented fusion was performed in the second stage. All patients were clinically evaluated by mJOA, VAS and Frankel score preoperatively, at 6 months and at 1 year postoperatively. The radiologic evaluation assessed the instrumentation failure, spinal fusion and kyphosis progression measured by sagittal Cobb angle. RESULTS The mJOA values improved from the mean preoperative value of 1.6 to 13.15 (6M) and 13.3 (1Y) postoperatively (p = 0.055). The VAS score increased from the mean value of 8.5 preoperatively to 2.15 (6M) and 1.35 (1Y) postoperatively (p < 0.001). No patient reported worse neurological finding postoperatively. The kyphosis progression measured by sagittal Cobb angle from the preoperative +6.7 decreased to +3.2 degrees at 1 year after surgery. The group of 12 patients treated in the acute phase of infection by anterior debridement without anterior column reconstruction showed worsening of kyphosis from +1.1 before surgery to +1.6 degrees at 1 year after surgery. The group of eight patients treated in the chronic phase by anterior debridement and reconstruction of the anterior column by implant changed from +15.9 before surgery to +6.1 degrees at 1 year after surgery. In two out of 12 patients with neurological deficit, the T2-weighted MRI finding of signal hyperintensity showed no improvement of the neurological deficit. DISCUSSION In the group of all operated patients, neither the worsening in the clinical evaluation using the mJOA or VAS score, nor kyphosis progression measured by Cobb angle in the sagittal plane, or failure of instrumentation in the anteroposterior procedure were reported postoperatively. In a total of nine patients operated on during the chronic phase of infection, in whom titanium implant was used to reconstruct the anterior column defect, no recurrent deep infection was observed. CONCLUSIONS In the acute phase we prefer anterior debridement with epidural abscess evacuation without anterior column reconstruction and posterior instrumented fusion in case of kyphosis progression in the second stage. In the chronic phase, radical anterior debridement with titanium implant reconstruction, eventually with posterior instrumented fusion is preferred. Key words: cervical spondylodiscitis, epidural abscess, anterior debridement, bacterial biofilm.

Insights into the physiology of C-peptide.

Current knowledge suggests a complex role of C-peptide in human physiology, but its mechanism of action is only partially understood. The effects of C-peptide appear to be variable depending on the target tissue, physiological environment, its combination with other bioactive molecules such as insulin, or depending on its concentration. It is apparent that C-peptide has therapeutic potential for the treatment of vascular and nervous damage caused by type 1 or late type 2 diabetes mellitus. The question remains whether the effect is mediated by the receptor, the existence of which is still uncertain, or whether an alternative non-receptor-mediated mechanism is responsible. The Institute of Endocrinology in Prague has been paying much attention to the issue of C-peptide and its metabolic effect since the 1980s. The RIA methodology of human C-peptide determination was introduced here and transferred to commercial production. By long-term monitoring of C-peptide oGTT-derived indices, the Institute has contributed to elucidating the pathophysiology of glucose tolerance disorders. This review summarizes the current knowledge of C-peptide physiology and highlights the contributions of the Institute of Endocrinology to this issue.

Endocrine disruptors, obesity, and cytokines - how relevant are they to PCOS?

As environmental and genetic components contribute to the PCOS expression, we compared levels of endocrine disruptors, steroid hormones, cytokines, and metabolic parameters in twenty healthy, nine normal-weight PCOS women, and ten obese PCOS women. Steroid hormones, bisphenols (BPA, BPS, BPF, BPAF) and parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-parabens) were measured by liquid chromatography-tandem mass spectrometry. Differences between the groups were assessed using the Mann-Whitney U test. Spearman correlation coefficients were calculated for the individual parameters relationship. Significantly higher levels of BPA, anti-Müllerain hormone, lutropine, lutropine/folitropine ratio, testosterone, androstenedione, 7beta-OH-epiandrosterone, and cytokines (IL-6, VEGF, PDGF-bb), were found in normal-weight PCOS women compared to controls. Between normal-weight and obese PCOS women, there were no differences in hormonal, but in metabolic parameters. Obese PCOS women had significantly higher insulin resistance, fatty-liver index, triglycerides, cytokines (IL-2, IL-13, IFN-gamma). In healthy, but not in PCOS, women, there was a positive correlation of BPA with testosterone, SHBG with lutropine, and folitropine, while testosterone negatively correlated with SHBG. In obese women with PCOS, insulin resistance negatively correlated with SHBG and estradiol. No differences were observed in the paraben exposure. Levels of BPA were higher in PCOS women, indicating its role in the etiology. Obesity significantly worsens the symptoms.

Familial hypocalciuric hypercalcemia in an index male: grey zones of the differential diagnosis from primary hyperparathyroidism in a 13-year clinical follow up.

Familial hypocalciuric hypercalcemia (FHH) type 1, caused by a heterozygous inactivating mutation of the gene encoding the calcium-sensing receptor (CaSR), is characterized by mild to moderate hypercalcemia, hypocalciuria and inappropriately normal or elevated parathyroid hormone (PTH). FHH must be differentiated from primary hyperparathyroidism (PHPT) because parathyroidectomy is ineffective in the former. Herein, we report a 39-year-old male patient with a 13-year history of asymptomatic PTH-dependent hypercalcemia (mean calcium of 2.88 mmol/l; reference range 2.15-2.55 mmol/l) and calcium-to-creatinine clearance ratio (Ca/Cr) ranging from 0.007 to 0.0198, which is consistent with either FHH or PHPT. Although a family history of hypercalcemia was negative, and PET-CT with fluorocholine was suggestive of a parathyroid adenoma, genetic analysis of the CaSR gene identified a heterozygous inactivating mutation NM_000388.4:c.1670G>A p. (Gly557Glu) in exon 6 and a polymorphism NM_000388.4:c.1192G>A p. (Asp398Asn) in exon 4. The G557E mutation has been previously reported in a Japanese family in which all family members with the mutation had Ca/Cr below 0.01 consistent with FHH. The biochemical profile of FHH and PHPT may overlap. Our FHH patient with a G557E CaSR mutation illustrates that the differential diagnosis can be difficult in an index case with no family history, (false) positive parathyroid imaging and higher calciuria than expected for FHH. Calcium intake, vitamin D status and bone resorption might have contributed to the Ca/Cr variations over a 13-year clinical follow up. This case thus emphasizes the irreplaceable role of genetic testing of the CaSR gene when clinical evaluation is inconclusive.

Plasma levels of adipokines in patients with Alzheimer's disease - where is the "breaking point" in Alzheimer's disease pathogenesis?

Peripheral insulin resistance is associated with decreasing adiponectin and increasing leptin plasma levels, and also with cognitive decline. The effects of adipokines on brain function have been published from both animal and human studies. In particular, the influence of leptin and adiponectin on the development of Alzheimer's disease (AD) has been extensively investigated. However, the association between adipsin and AD is as yet unknown. In 37 patients with AD and 65 controls that followed the same study protocol, we tested whether adiponectin, leptin, and adipsin could be used as biomarkers in the early stages of AD. In contrast with conclusions of cognition studies in insulin resistant states, our study found a correlation of impaired neuropsychological performance with increasing adiponectin and decreasing leptin in AD patients. Nevertheless, no significant differences between patients and controls were found. AD women had significantly increased adipsin compared to controls, and there was a positive correlation of adipsin with age and disease duration. Although adipokines do not appear to be suitable biomarkers for early AD diagnosis, they certainly play a role in the pathogenesis of AD. Further studies will be needed to explain the cause of the adipokine "breaking point" that leads to the pathogenesis of overt AD.

Genetic predictors of the development and recurrence of Graves' disease.

Graves' disease affects approximately 3 % of women and 0.5 % of men. The first-choice therapy is based on the administration of thyrostatic drugs. However, approximately half of patients relapse within two years of discontinuation. These patients must then decide whether to re-initiate thyrostatics, which may have serious side effects, or to undergo surgery or radioiodine treatment. Familial forms of Graves' disease indicate a significant genetic component, with twin studies demonstrating a contribution of genetic factors up to 70-80 %. The autoimmune nature of the disease involves the human leukocyte antigen (HLA) complex, which has a decisive impact on each individual's immune response. Within HLA, some variants of the DRB1, DQA1 and DQB1 genes appear to be possible predictors of the development and recurrence of Graves' disease. Outside the HLA region, many variants of immunocompetent genes have also been identified as potential Graves' disease predictors. Apart from the immune system, some thyroid-specific genes have been described in relation to the disease. Here, we present current knowledge regarding the genetic components involved in the development and recurrence of Graves' disease. Further, we present original pilot results from a cohort of Czech Graves' disease patients regarding the HLA variants.

Parabens and their relation to obesity.

Parabens are a group of chemicals used as preservatives in the food, cosmetic and pharmaceutical industries. They are known to possess estrogenic effects, and therefore have been classified as endocrine disruptors. In addition to the classical endocrine organs, other tissues have endocrine activity, including adipose tissue. Several chemicals are known to cause obesogenic effects, and parabens are currently being studied in this context. The aim of this study was to investigate the possible connections of paraben exposure and obesity. Blood plasma from 27 healthy women was collected during their menstrual cycle. Basal anthropometric measures, levels of parabens (methylparaben, ethylparaben and propylparaben), adipokines (adiponectin, adipsin, leptin, resistin and visfatin) and hormones affecting energy balance and metabolic health (c-peptide, ghreline, GIP, GLP-1, glucagon, insulin, PAI-1) were measured. A Kolmogorov-Smirnov test showed higher methylparaben and propylparaben levels in women with BMI 25-34.9 compared to those with BMI 18.5-24.9. Plasma levels of methylparaben as well as the sum of parabens were positively associated with the plasma adipsin levels. Negative associations for methylparaben were found for glucagon, leptin and PAI-1. In accordance with other experimental studies we observed important associations of methylparaben and hormones affecting energy balance and metabolic health, indicating its obesogenic potential.

Expression profiling of Nme7 interactome in experimental models of metabolic syndrome.

Nucleoside diphosphate kinase 7, non-metastatic cells 7 (NME7) is an acknowledged member of ciliome and is involved in the biogenesis or function of cilia. As obesity and diabetes are common in several ciliopathies, we aimed to analyze changes of gene expression within Nme7 interactome in genetically designed rat models of metabolic syndrome. We assessed the liver transcriptome by Affymetrix microarrays in adult males of 14 PXO recombinant inbred rat strains and their two progenitor strains, SHR-Lx and BXH2. In the strains with the lowest expression of Nme7, we have identified significant enrichment of transcripts belonging to Nme7 interactome. In the subsequent network analysis, we have identified three major upstream regulators - Hnf4a, Ppara and Nr1h4 and liver steatosis (p=0.0001) and liver necrosis/cell death (apoptosis of liver cells, p=0.0003) among the most enriched Tox categories. The mechanistic network reaching the top score showed substantial overlap with Assembly of non-motile cilium and Glucose metabolism disorder gene lists. In summary, we show in a genetic model of metabolic syndrome that rat strains with the lowest expression of Nme7 present gene expression shifts of Nme7 interactome that are perturbing networks relevant for carbohydrate and lipid metabolism as well as ciliogenesis.

[Anterior Cruciate Ligament Tears - Influence on Terminal Extension]. / Ruptury predního zkrízeného vazu ­ vliv na terminální extenzi.

PURPOSE OF THE STUDY The aim of this paper was to compare terminal extension in normal and anterior cruciate ligament (ACL) deficient knees, and therefore to determine the role of the ACL during this motion. MATERIAL AND METHODS Ten knees with ACL tears (7 knees with recent ACL tears, 3 knees with long-standing tears) and 10 normal contralateral knees have been examined using MRI in passive hyperextension, 20° flexion and 20° flexion with a 9 kg posteriorly directed load on the femur. Movements of the femoral condyles on the tibia were calculated using previously described methods. RESULTS 1. Under the load at 20° flexion, knees with ACL tear showed posterior femoral subluxation (equivalent to a Lachman test), chronic tears being more unstable. Contralateral normal knees were antero-posteriorly stable. In hyperextension, both femoral condyles subluxed posteriorly in ACL tears but not in normal knees. 2. In all knees with ACL tear, the lateral femoral condyle moved posteriorly from hyperextension to 20°, equating to femoral external rotation. 3. The longitudinal rotation axis during terminal extension in normal knees was medial but in ACL tears it was central causing the medial femoral condyle to move forward from hyperextension to 20°. In normal knees, the medial femoral condyle did not move antero-posteriorly from hyperextension to 20° flexion. DISCUSSION Internal rotation of the femur during terminal extension has been recognized for 150 years. The question remains: what causes the usual combination of longitudinal rotation and extension? In the current literature ACL is considered to be responsible for internal rotation of the femur during terminal extension of the knee. So far, as we are aware, the kinematics of terminal extension, including hyperextension, have not been reported after ACL tear in the living knee. CONCLUSIONS Results of this study imply that: 1. The ACL prevents anterior tibial subluxation in hyperextension. 2. The ACL does not cause rotation in terminal extension. 3. The ACL locates the axis of longitudinal rotation in terminal extension. We hope that by studying living knees with and without ACL tear we may not only clarify the nature and mechanism of rotation in terminal extension, and hence the role of the ACL, but do so in a context of direct clinical relevance. Key words: knee, terminal extension, ACL tear, axis of longitudinal rotation, antero-posterior instability, MRI.

[Two-Stage Revision for Periprosthetic Infection of the Total Hip Arthroplasty: a Comparison of Two Methods]. / Srovnání klinických výsledku skupiny pacientu neartikulovaného a artikulovaného spaceru pri dvoudobé reimplantaci TEP kycelního kloubu pro periprotetický infekt.

PURPOSE OF THE STUDY The purpose of the study is a retrospective comparison of results of the two-stage revision total hip arthroplasty using a non-articulating and an articulating spacer to treat periprosthetic joint infection (PJI). Two basic hypotheses are evaluated: (1) the clinical outcomes of the patients treated with "hand made" articulating cement spacer are better than in non-articulating patient's group in two-stage revision for PJI of the total hip arthroplasty and (2) PJI recurrence is higher in the group of patients treated with an articulating spacer group. MATERIAL AND METHODS The evaluated group consists of a total of 57 patients (23 women, 34 men) with the mean age of 61.2 years. Group A of 39 patients were treated by two-stage revision using the "hand-made" articulating cement spacer and Group B of 18 patients were treated using the non-articulating spacer. Both the groups were evaluated retrospectively in the reference period: preoperatively and two years after the surgery using the Harris Hip Score (HHS) clinical assessment. The revision surgery for acute and chronic complications of treatment, length of hospitalization, and the PJI recurrence were evaluated for both the groups. RESULTS The resulting HHS clinical reviews were pre-operatively 43.59 points in both the groups with postoperative improvement up to 81.74 points. The mean preoperative HHS scores were 41.67 points (Group A) and 47.77 points (Group B) and two years after the surgery they were 83.43 points (Group A) and 78.08 points (Group B) (two-tailed t-test, p-value = 0.042). In Group A a total of seven revisions were performed in the interval between the two-stage revision (4x recurrent dislocation, 2x persistent infection, 1x spacer fracture). In Group B one patient was revised for persistent infection. In the two-year period after the operation, a relapse of PJI was recorded in 5 patients in Group A (12.8%) and in 1 patient in Group B (5.6%) (Chi-square test, p-value = 0.41). The average time of hospitalization was 51.58 days, whereby 49.72 days and 55.61 days on average for Group A and B respectively (p-value = 0.53). DISCUSSION According to recent studies, the advantage of motion preservation in articulating cement spacers can be complicated by recurrent dislocations, implant migration, periprosthetic fractures or recurrent joint replacement infections, which can further prolong the treatment and worsen the final clinical results. An alternative treatment option is the application of a nonarticulating spacer maintaining the advantage of local administration of antibiotics and reducing the dead space formed by the infected implant removal. Discussed is mainly the choice of the method in case of muscle disorder or presence of segmental bone defects. CONCLUSIONS The results demonstrate the better clinical outcomes and the higher revision rate of patients with an articulating cement spacer in two stage revision. We didn't find any differences between the risk of PJI recurrence in both groups. Key words:periprosthetic infection, total hip replacement, cement spacer, two stage revision, articulating spacer, nonarticulating spacer.

Specific metabolic characteristics of women with former gestational diabetes: the importance of adipose tissue.

Women with a positive history of gestational diabetes mellitus (GDM) face a higher risk of developing type 2 diabetes mellitus (T2DM) and metabolic syndrome later in life. The higher risk of these metabolic complications is closely associated with adipose tissue. In this review, the importance of adipose tissue is discussed in relation to GDM, focusing on both the quantity of fat deposits and the metabolic activity of adipose tissue in particular periods of life: neonatal age, childhood, adolescence, and pregnancy followed by nursing. Preventive measures based on body composition and lifestyle habits with special attention to the beneficial effects of breastfeeding are also discussed.

ZBTB16 and metabolic syndrome: a network perspective.

Metabolic syndrome is a prevalent, complex condition. The search for genetic determinants of the syndrome is currently undergoing a paradigm enhancement by adding systems genetics approaches to association studies. We summarize the current evidence on relations between an emergent new candidate, zinc finger and BTB domain containing 16 (ZBTB16) transcription factor and the major components constituting the metabolic syndrome. Information stemming from studies on experimental models with altered Zbtb16 expression clearly shows its effect on adipogenesis, cardiac hypertrophy and fibrosis, lipid levels and insulin sensitivity. Based on current evidence, we provide a network view of relations between ZBTB16 and hallmarks of metabolic syndrome in order to elucidate the potential functional links involving the ZBTB16 node. Many of the identified genes interconnecting ZBTB16 with all or most metabolic syndrome components are linked to immune function, inflammation or oxidative stress. In summary, ZBTB16 represents a promising pleiotropic candidate node for metabolic syndrome.

ZBTB16 gene variability influences obesity-related parameters and serum lipid levels in Czech adults.

The data derived from rat models and the preliminary results of human studies provide strong indices of involvement of common ZBTB16 variants in a range of cardiovascular and metabolic traits. This cross-sectional study in the Caucasian cohort of 1517 Czech adults aimed to verify the hypothesis that ZBTB16 gene variation directly affects obesity and serum lipid levels. Genotyping of nine polymorphisms of the ZBTB16 gene (rs11214863, rs593731, rs763857, rs2846027, rs681200, rs686989, rs661223, rs675044, rs567057) was performed. A multivariate bidirectional regression with the reduction of dimensionality (O2PLS model) revealed relationships between basal lipid levels and anthropometric parameters and some minor ZBTB16 alleles. In men, the predictors - age and presence of minor ZBTB16 alleles of rs686989, rs661223, rs675044, rs567057 - were associated with significantly higher body mass index, waist to hip ratio, body adiposity index, waist and abdominal circumferences, higher total cholesterol and LDL cholesterol and explained 20 % of variability of these variables. In women, the predictors - age and presence of the rs686989 minor T allele - were also associated with increased anthropometric parameters and total cholesterol and LDL cholesterol but the obtained O2PLS model explained only 7.8 % of the variability of the explained variables. Our study confirmed that the selected gene variants of the transcription factor ZBTB16 influence the obesity-related parameters and lipid levels. This effect was more pronounced in men.