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The standard first-line systemic treatment for patients with non-oncogene addicted advanced nonsquamous non-small cell lung cancer (NSCLC) is immunotherapy with immune checkpoint inhibitors (ICI) and/or chemotherapy (ChT). Therapy after failing ICI +/− ChT remains an open question, and docetaxel plus nintedanib represent a valid second line option.

A case of an intratemporal lobe and middle cranial fossa neurinoma of the facial nerve is presented. Complete excision of the tumour was carried out. [ABSTRACT FROM AUTHOR]

Background. Glioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients. Materials and methods. We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM.

Lesions composed of Pacinian corpuscles or showing Pacinian corpuscle differentiation have usually been described in relation to benign tumours of the peripheral nervous system or reactive hyperplastic processes. On the other hand, mature Pacinian corpuscles have occasionally been detected as part of intraspinal lumbosacral lipomas, a rare developmental anomaly usually associated with spina bifida. A lesion of the cauda equina composed of numerous mature Pacinian corpuscles and nerve fascicles embedded in adipose tissue in association with spina bifida occulta is described in a 5-month-old male with a sacral red papula. Magnetic resonance imaging (MRI) revealed a cord-like mass in the region of the cauda equina, presumably connected to the subcutis. With the exception of a low lying, tethered spinal cord, there was no neurological deficit and the range of motor development was normal. In March 2005, at 17 months, surgery was carried out. A cord of yellow tissue was found running from the subcutis through the bone defect into the lumbosacral spinal canal. Intradurally, it ran parallel to the cauda equina, terminating at the conus medullaris. Fifteen months after the surgery the development of the child was normal. Only two similar cases have been reported so far. Due to their occurrence in the sacrococcygeal region and association with developmental anomalies, they have been regarded as malformations and the term Pacinioma has been suggested. Our case with clusters of Pacinian corpuscles may represent a rare variant of complex intraspinal lumbosacral lipomas, closely related to Paciniomas reported by Bale. [ABSTRACT FROM AUTHOR]

Aim: Alongside the proven efficacy, immunotherapy in treatment of malignant diseases can cause immune-related adverse events different from commonly known chemotherapy-related toxicities., Case Presentation: During nivolumab treatment of metastatic squamous cell lung cancer, the patient developed a symptomatic inflammatory myositis confirmed with muscle biopsy and primary hypothyroidism. After initiation of corticosteroids and thyroid hormone replacement, the clinical and laboratory improvement occurred. To the best of our knowledge, this is the first description of a case of nivolumab-induced synchronous manifestation of immune-related myositis and hypothyroidism., Conclusion: Immunotherapy can trigger a wide spectrum of immune-related adverse events that could occur simultaneously. If not detected and treated, these events could become severe or even fatal and require clinicians' awareness and routine check-ups.

Background: Lung cancer is the leading cause of cancer deaths and the non-small cell lung cancer (NSCLC) represents 80% of all cases. In most cases when diagnosed, it is in locally advanced or metastatic stage, when platinum based doublet chemotherapy is the established therapeutic option for majority of the patients. Predictive factors to filter the patients who will benefit the most from the chemotherapy are not clearly defined. Objective of this study was to explore predictive value of pre-treatment C-reactive protein (CRP), fibrinogen and their interaction, for the response to the frontline chemotherapy., Methods: In this retrospective cohort study 170 patients with locally advanced and metastatic NSCLC were included. Relationship between baseline level of CRP and fibrinogen and response to the frontline chemotherapy was assessed., Results: We found that pre-treatment CRP and fibrinogen values were statistically significantly correlated. Chemotherapy and CRP, fibrinogen, and their interaction were independently significantly associated with disease control rate at re-evaluation. There was statistically significant difference in median pre-treatment CRP level between the patients with disease control or progression at re-evaluation, 13.8 vs. 30.0 mg/L respectively, P=0.026. By Johnson-Neyman technique we found that in patients with initial fibrinogen value below 3.5 g/L, CRP level was significantly associated with disease control or progression of the disease. Above this fibrinogen value the association of CRP and disease control was lost., Conclusions: The findings from this study support the growing evidence of inflammation and cancer relationship, where elevated pre-treatment level of CRP has negative predictive significance on the NSCLC frontline chemotherapy response.

Aim: The aim of this study is to investigate whether there was a considerable difference in the survival of patients with malignant pleural effusion (MPE) depending on the pleural effusion treatment option., Methods: One hundred and seven patients with proven MPE (metastatic lung and breast cancer) were included in the retrospective study. Fifty six patients were treated with talc pleurodesis and a control group of 51 patients with similar characteristics (in age, sex and disease) were treated with serial thoracentesis. The patients of both groups underwent chemotherapy and/or radiotherapy. The overall survival and the survival in subgroups of patients with different tumour types and different performance status (PS) equal 1, 2 and 3 were compared., Results: The patients who underwent talc pleurodesis had a longer average survival interval (MS) than the patients without such a treatment (n = 56; MS = 21,5 and n = 51; MS = 9 weeks, respectively; p < 0.001). The best results were achieved in patients with PS 1 (n = 16; MS = 35.5 and n = 10; MS = 11 weeks in the groups with and without talc pleurodesis, respectively; p < 0,001) and PS 2 (n = 27; MS = 21 and n = 30; MS = 10 weeks in the groups with and without talc pleurodesis, respectively; p < 0.001), whereas talc pleurodesis was not effective in PS 3 patients (n = 13; MS = 10 and n = 11; MS = 7 weeks in the groups with and without talc pleurodesis, respectively; p = 0.08). Patients with the breast cancer showed a longer average survival interval after pleurodesis than those with the lung cancer (n = 12; MS = 37.5 and n =  4; MS = 20 weeks in the group with the breast cancer and with the lung cancer, respectively; p < 0.001), whereas the median survival was not significantly different between those patients without pleurodesis (n = 10; MS = 10 and n = 41; MS = 9 weeks in the group with the breast cancer and lung cancer, respectively; p = 0.11)., Conclusion: The patients treated with talc pleurodesis had a significantly longer average survival than the patients without such a treatment, especially in the group with the breast cancer and in groups with better performance status. This may indicate that talc pleurodesis, apart from its symptomatic effect on the cessation of pleural effusion, may have a direct antitumour effect as well.

Interhemispheric cysts, often associated with agenesis of corpus callosum, are rare lesions. The optimal treatment is still controversial. Placement of cystoperitoneal shunt and open microsurgery are traditional treatments. Neuroendoscopy in children is due to its minimal invasiveness a new emerging option. There have been a few published cases on neuroendoscopic treatment of interhemispheric cyst in children. The authors document the youngest reported child with multiloculated interhemispheric cyst that was treated with neuroendoscopy. The cyst was detected in a male fetus in 35th week of gestation and in utero magnetic resonance imaging was performed in 37th week of gestation. After delivery, progressive macrocrania with signs of raised intracranial pressure developed. Endoscopic cystoventriculocisternostomy was performed 28 days after the birth. There was a marked symptom relief. One month after the surgery, magnetic resonance showed shrinkage of the cyst and expansion of the brain parenchyma. After a 2-month follow up period, the child showed normal neurologic development and head circumference increased by only 0.5 cm. The created fenestrations enabled the brain to expand. Neuroendoscopic treatment,of interhemispheric cysts should be considered the operative technique of choice in newborns. Although the intracranial pressure and the size of the cyst have decreased, long-term follow up is necessary and future studies on more cases are needed.

Excess weight and obesity are common health problems with multifactorial and polygenic causes. Abdominal or visceral obesity is associated with a higher risk of obesity related complications. The aim of the study was to evaluate differentially expressed genes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of 10 overweight women undergoing elective laparoscopic cholecystectomy. Following expression profiling using microarrays, a set of 294 genes that exhibited differential expression between VAT and SAT was further analyzed to test the functional correlation of gene sets using the Gene Set Enrichment Analysis method. To confirm the functional pathways involved in differential expression between SAT and VAT, additional pathway analysis was done using the GeneGo MetaCore software and the Ingenuity Pathway Analysis. Ten differentially expressed genes were selected according to the microarray data, with seven exhibiting significant differential expression in the RT-PCR experiments. The data from this preliminary study suggest enrichment of inflammation and oxidative stress related pathways in VAT, while insulin homeostasis pathways as well as pathways pertaining to several growth factors are enriched in SAT.

Objective: To examine the prognostic ability of protein S100B, neuron-specific enolase (NSE) and glial fibrillary acid protein (GFAP) for prediction of 1-year mortality in patients with traumatic brain injury (TBI) in relation to clinical and radiological characteristics of TBI., Methods: Brain injury was quantified in 84 patients (Glasgow Coma Scale [GCS] ≤ 12) using clinical (GCS, pupils), radiological (computed tomography [CT] classification and individual CT characteristics) and biochemical (S100B, NSE and GFAP) data at admission and in the acute post-injury period., Results: Initial and peak S100B, NSE and GFAP concentrations were higher in non-survivors (n = 26) than in survivors (p-value range: <0.001-0.018). Cox regression showed that GFAP and S100B concentration and the temporal profile of S100B were more powerful independent predictors of mortality than baseline clinical and radiological characteristics or clinical and radiological indicators of neurological deterioration. The prognostic models containing admission variables and those available during the subsequent clinical course showed the same discrimination ability (area under receiver characteristic curve 0.92), but the model based on variables available in the acute post-injury period calibrated better (p = 0.428)., Conclusion: Mortality at 1-year post-TBI is accurately predicted by the combination of GFAP and S100B concentration and clinical and radiological characteristics at admission or in the acute post-injury period.

The objective of the present study was to examine several dimensions of quality of life (QoL) and fatigue in patients with adrenal incidentaloma. This was a case-control study designed to analyze patient outcomes using three validated generic QoL questionnaires, EQ-5D, SF-36, and MFI-20, the results of which were compared to those obtained for age- and sex-matched controls. The study population comprised 139 consecutive patients with nonfunctioning adrenal masses (104 females, 35 males; age 59.1 ± 10.8) and 139 age- and sex-matched controls. Reduced QoL was found in patients with adrenal incidentaloma as compared to controls. Dimensions of QoL that were notably affected included mobility (P = 0.03), performance of usual activities (P = 0.002), and anxiety/depression (P = 0.04) as evaluated using the EQ-5D; physical functioning (P < 0.001), physical role (P < 0.001), general health (P < 0.001), vitality (P = 0.001), social functioning (P = 0.001), and emotional role (P < 0.001) as evaluated using the SF-36; and physical fatigue (P = 0.04) as assessed using the MFI-20 questionnaire. In addition, perceived health on a visual analogue scale was also significantly lower in patients than in controls (64.8 ± 19.2 vs. 77.1 ± 15.1; P < 0.001). Patients with adrenal incidentaloma reported reduced QoL and a higher level of physical fatigue compared to age- and sex-matched controls. This subject will benefit from further studies comparing QoL outcomes of laparoscopic adrenalectomy versus no treatment in patients with adrenal incidentaloma.

Vitamin D deficiency is associated with secondary hyperparathyroidism, increased bone turnover, and bone loss, leading to increased risk for osteoporotic fractures. The objective of this study was to investigate the prevalence of inadequate (insufficient or deficient) serum vitamin D levels in Croatian postmenopausal women initially screened for osteoporosis. Assessment of 25-hydroxyvitamin D (25(OH)D) was performed in 120 Croatian postmenopausal women aged > or =50 years. Three cut-off levels of vitamin D inadequacy were investigated: <75, <50, and <30 nmol/L. Among the included patients, only 14.2% of women complied with diagnostic criteria for osteoporosis. A total of nine (7.5%) had vitamin D levels greater than 75 nmol/L, suggesting that 92.5% of postmenopausal women had inadequate vitamin D status. The prevalence of two different cut-off point groups was 63.3% (<50 nmol/L) and 14.2% (<30 nmol/L). Mean (+/-SD) serum level of 25(OH)D was 46.94 (16.77) nmol/L. Vitamin D was exhibiting declining values with increasing age (r = -0.28; P = 0.002). The prevalence of vitamin D levels below 30 nmol/L was high in patient aged > or =65 years (23.8%). The highest mean level of vitamin D was detected in summer, with significant differences from spring and winter (P = 0.015 and P = 0.022, respectively). The results of this study indicate a high prevalence of vitamin D inadequacy in Croatian postmenopausal women initially screened for osteoporosis. High prevalence coupled with the rising recognition of potential clinical significance of the vitamin D inadequacy makes this highly interesting intervention target, suggesting that the attempts to increase the awareness on this issue are needed.

Objective: The present study was designed to assess the effect of monthly ibandronate on health-related quality of life (HR-QoL) in patients with postmenopausal osteoporosis previously treated with weekly bisphosphonates., Methods: HR-QoL was assessed by Euroqol (EQ-5D) and Osteoporosis Targeted Quality of Life (OPTQoL) questionnaires., Results: The EQ-5D questionnaire showed significant improvement associated with ibandronate treatment, occurring in mobility (p < 0.01), usual activity (p < 0.01), pain/discomfort (p < 0.05), and anxiety/depression (p < 0.05). In addition, ibandronate treatment considerably improved patients' perceived health on a visual analog scale (p < 0.001). For the OPTQoL questionnaire, patients reported less physical difficulty (p < 0.001), fewer adaptations in their lives (p < 0.001), and less fear (p < 0.001) with ibandronate than with weekly bisphosphonates., Conclusion: The study demonstrated that patients who were transferred from weekly bisphosphonates to a monthly ibandronate experienced improved HR-QoL.

Objective: Hypercoagulability is a commonly described complication in patients with Cushing's syndrome. Recent clinical studies have indicated various abnormalities of coagulation and fibrinolysis parameters which may be related to that phenomenon. The aim of this study was to investigate the mechanisms underlying the hypercoagulable state in patients with Cushing's syndrome., Research Methods and Procedures: A wide range of serum markers involved in the processes of blood coagulation and fibrinolysis was measured in a group of 33 patients with Cushing's syndrome and 31 healthy controls. No participant was taking medication which could influence the result or had known diseases, except hypertension and diabetes, which could affect blood coagulation or fibrinolysis parameters., Results: Patients with Cushing's syndrome had higher levels of clotting factors II (P = 0.003), V (P < 0.001), VIII (P < 0.001), IX (P < 0.001), XI (P < 0.001) and XII (P = 0.019), protein C (P < 0.001), protein S (P < 0.001), C1-inhibitor (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (P = 0.004). The activity of fibrinolytic markers, plasminogen (P < 0.001), antithrombin (P < 0.001) and antithrombin antigen (P = 0.001) was also increased in the patient group., Conclusion: The study has demonstrated hypercoagulability in patients with Cushing's syndrome manifest as increased prothrombotic activity and compensatory activation of the fibrinolytic system. We propose the introduction of thromboprophylaxis in the preoperative and early postoperative periods, combined with a close follow-up in order to prevent possible thromboembolic events in patients with Cushing's syndrome.

The objective was to investigate the association of nutrients and lifestyle modifiers with bone mineral density (BMD) and weight and/or body mass index (BMI) in 120 healthy Croatian postmenopausal women. The hip and spine BMD was assessed by Lunar Prodigy (GE Medical Systems). Nutrient assessment from 3-day records was analyzed using the US Department of Agriculture Food Composition Tables and the Croatian National Institute of Public Health database. Subjects were asked to record the consumption of alcohol, coffee, tea and mineral waters, the amount of salt added to foods and smoking habits, as well as involvement in recreational activities, walking and heavy housework. Spot urine samples were analyzed for calcium, magnesium, sodium, potassium and zinc and were normalized by creatinine. Alcohol showed statistically significant positive association with femur and spine BMD and its consumption was higher in subjects without osteoporosis. Urinary sodium/creatinine was significantly positively associated with femoral neck and trochanter BMD, while urinary calcium/creatinine was significantly negatively associated with trochanter, total femur and spine BMD. Consumption of mineral waters was inversely associated with weight/BMI and so were dietary fiber and magnesium. In conclusion, moderate alcohol consumption and urinary sodium were positively associated while urinary calcium was negatively associated with either hip and/or spine BMD. Mineral waters, higher fiber and magnesium intake were beneficial for weight/BMI in this population of apparently healthy Croatian women.

The PROMO (preference for once monthly bisphosphonate) Study, conducted in seven hospital centres in Croatia between June 2007 and June 2008, was designed to analyse patient preference for weekly and monthly bisphosphonates in everyday clinical practice where the significant proportion of patients are not completely satisfied with the current osteoporosis treatment. Eligible participants were women with postmenopausal osteoporosis taking weekly bisphosphonates for the last 6 months. Those who agreed to be enrolled were transferred from weekly to monthly ibandronate for the next 6 months. There was no washout period between the two treatment regimens. At the baseline, patients expressed their satisfaction with the weekly treatment. At the end of the study, all patients were asked to complete the five-question survey specially designed for this study. Study population comprised 258 participants. Among 248 patients who completed the study, 244 (98.4%) declared their preference for one of the regimens or they had no preference. Once-monthly regimen was preferred by 231 patients (94.7%), whereas once-weekly regimen was preferred by five patients (2.0%). Eight patients (3.3%) indicated no preference. Furthermore, 93.0% of patients thought that monthly dosing was more convenient. Compared to weekly regimen, monthly dosing was associated with significantly higher satisfaction with the treatment and with significantly less adverse events. In line with these data, 85.9% of patients stated improved quality of life with monthly ibandronate. In summary, the PROMO Study demonstrated strong patient preference for monthly over weekly dosing which is expected to improve suboptimal adherence to weekly bisphosphonates.

Idiopathic osteoporosis in males is influenced predominantly by low peak bone mass as a feature under a strong genetic control. Among a number of candidate genes, alpha-estrogen receptor (ERalpha) and CYP19 genes are of particular interest due to important role of estrogen in pathophysiology of osteoporosis. In the present study we examined the association of certain allelic combinations of ERalpha gene thymine-adenine (TA) polymorphism and aromatase gene TTTA polymorphism on bone mineral density (BMD) in young men. The study sample consisted of 92 unrelated healthy male volunteers, aged 21-35. In each subject, lumbar spine and proximal femur BMD, parameters of bone turnover and 25-OHD level were measured. Two ERalpha (TA)( n ) alleles, allele 19 and allele 21, were found to be associated with lower BMD. The presence of allele 19 was associated with significantly lower lumbar spine (P = 0.006) and trochanter (P = 0.02) BMD while the subjects positive for allele 21 had significantly lower lumbar spine (P = 0.04), trochanter (P = 0.02) and total hip (P = 0.03) BMD. Men with CYP19 (TTTA)(7-3)/ERalpha (TA)(19) allele combination had significantly lower lumbar spine BMD (P = 0.02) and those with CYP19 (TTTA)(7-3)/ERalpha (TA)(21) allele combination had significantly lower BMD for all three measurements, i.e. lumbar spine (P = 0.02), femoral neck (P = 0.02) and total hip (P = 0.008). These particular combinations of high-risk alleles were associated with lower median lumbar spine, femoral neck and total hip BMD than either of the allele alone suggesting that negative effect of two risk alleles on peak bone mass add up.

Background/aim: The relationship between the hypothalamic-pituitary-thyroid (HPT) axis and the serotonergic (5-hydroxytryptamine, 5-HT) system is not clear. The aim of the study was to determine platelet biochemical markers (5-HT concentration and monoamine oxidase B, MAO-B, activity) in hypothyroid patients., Methods: The study included 25 medication-free female hypothyroid patients in postoperative follow-up after total thyroidectomy due to papillary thyroid carcinoma, who had not been treated with synthetic thyroxine (T(4)) for 4 weeks, and 44 age-matched euthyroid healthy women. The platelet 5-HT concentration, platelet MAO-B activity, total T(4) and thyroid-stimulating hormone (TSH) levels were determined using spectrofluorimetric methods, radioimmunoassay and fluoroimmunoassay, respectively., Results: Hypothyroid patients had significantly higher TSH, significantly lower T(4) levels and platelet 5-HT concentrations, and unchanged platelet MAO-B activity than healthy subjects. A positive correlation was found between the 5-HT concentration and platelet MAO-B activity, and between the platelet MAO-B activity and T(4) in control subjects., Conclusions: Reduced platelet 5-HT concentrations in hypothyroid patients suggests a complex interaction between the 5-HT system and HPT axis activity, which could be related to the frequent occurrence of depressive symptoms in hypothyroid patients. The determination of platelet 5-HT concentrations should be considered a diagnostic tool for the evaluation of depressive symptoms in hypothyroid patients during the hormone withdrawal procedure., (2009 S. Karger AG, Basel.)

Although ibandronate improves suboptimal compliance in patients receiving weekly bisphosphonates, there is a concern about its effect on the reduction of nonvertebral fractures. In the era of evidence-based medicine, randomized clinical trials are considered the highest quality evidence which guide us to the best clinical decision. Nevertheless, if level 1 evidence is not available, as is the case with ibandronate, evidences of lower levels could be used to draw relevant clinical decision. In this article, we discussed data from clinical trials (subgroup analyses of high-risk patients, meta-analysis of clinical trials) which suggested significant effect of ibandronate on the risk reduction of nonvertebral fractures.

Background: The aim of this study was to compare quantitative ultrasound parameters between women and men of various ages in a population from central Croatia and also to estimate the prevalence of osteoporosis in women., Material/methods: A total of 1006 participants were recruited for this study (550 men, 456 women), aged 20 to 89 years. Calcaneal quantitative ultrasound measurements were performed using a Sahara device (Hologic). Data were analyzed using the t-test and analysis of variance (ANOVA) with Tukey's post hoc test., Results: Comparison of the ultrasound measures of the men exhibited significant differences across the age groups with the exception of broadband ultrasound attenuation (BUA). In the women, significant differences were found for BUA, speed of sound (SOS), and the quantitative ultrasound index (QUI). Gender comparison revealed significant differences between ultrasound parameters in the last three decade groups. Using a T-score threshold of -1.8, the prevalence of osteoporosis in women aged over 50 was 30.7% based on the quantitative ultrasound index., Conclusions: This study is the first report of quantitative ultrasound parameters in Croatian women. The results revealed lower QUI, BUA, and SOS in postmenopausal women than in men of the same age. The prevalence of osteoporosis in women over 50 years of age based on the quantitative ultrasound index was considerably higher than the previously reported prevalence of osteoporosis in men.

Growth hormone (GH) deficiency and acromegaly serve as good models for investigating the effects of GH on bone remodeling. However, the results from various studies are rather conflicting. The aim of our study was to estimate the potential role of gender, disease activity, and duration on both calcaneus quantitative ultrasound (QUS) parameters and bone turnover markers in patients with acromegaly. Thirty-six acromegalic patients (17 men, 19 women) and 3 age- and gender-adjusted controls for every patient were included in the study. The disease was active in 22 patients, and was considered cured in 14 of them. In each subject, QUS of the heel and parameters of bone turnover (bone alkaline phosphatase, beta-crosslaps, and osteocalcin) were measured. The results demonstrated lower QUS values in acromegalic patients compared with the controls. When stratified by gender, the differences in QUS parameters were significant in men, but not in women. Male patients with active disease had significantly lower QUS values than those in remission. Such differences were not observed among women. Multiple regression model indicated strong association between disease activity and the QUS parameters. The group of patients with active disease had a higher level of serum beta-crosslaps, whereas osteocalcin concentration was significantly increased only in male patients with active disease. The results of our study suggest significantly lower QUS values and increased bone turnover in male patients with active acromegaly. The disease activity is the strongest predictor of the QUS parameters in acromegalic patients.