Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

What do patients really know about cardiopulmonary rehabilitation: a cross-sectional survey study.

BACKGROUND: Although it is known that cardiopulmonary rehabilitation (CPR) reduces mortality and morbidity, it is not widely implemented as is in Turkey. One factor might be lack of demand since the levels of knowledge and awareness among patients who are eligible for CPR seem to be insufficient. AIM: It is aimed to investigate the level of awareness and knowledge of CPR among patients with cardiopulmonary problems. DESIGN: Cross-sectional survey study. SETTING: Outpatient. METHODS: Knowledge regarding CPR was assessed by questionnaires given to 690 patients recruited in seven university hospitals and six training and research hospitals in which either comprehensive or limited CPR services are available. POPULATION: Patients who have cardiopulmonary problems RESULTS: Of the patients, 34.7% were given information on CPR by healthcare staff, and 25.3% reported that their source of information was physicians. Although 49.9% of the patients knew that they needed to exercise for their cardiac/pulmonary problems, only 23.4% and 32.1% of those were aware that fast walking and climbing stairs, respectively, would not pose a risk to their cardiac/pulmonary health. The majority of the patients believed that activities of daily living, which comprise the most important component of exercise-based CPR, were harmful for their cardiopulmonary health. We found that 31.1% of the patients exercised regularly. During their stay at the hospital, certain kinds of exercises were suggested to 62.7% of the patients, and 34.7% of these patients performed various exercises. Of the patients who were given detailed information on cardiopulmonary rehabilitation, 69% stated that they would be willing to participate in a similar program. CONCLUSION: Although nearly half of the patients stated that they needed CR, it was observed that the ratio of patients who had true knowledge of CPR was low among patients. It is imperative to furnish patients with information on CPR, both in the field of PMR and throughout Turkey, and to put more effort into running those services effectively. Furthermore, we should make an effort to increase the level of liaison between patients and physicians and other healthcare professionals who participate in the treatment of cardiac/pulmonary patients.

Reduced aerobic capacity in patients with severe osteoporosis: a cross sectional study.

AIM: It has been previously shown that pulmonary function (PF) is significantly diminished in patients with osteoporosis (OP). But there are few data about the relationship between PF and aerobic capacity of osteoporotic patients and the severity of thoracic kyphosis and time since the diagnosis of OP. The aim of the present study was to investigate the resting spirometric values and cardiopulmonary test (CPET) results of women with osteoporosis and to evaluate the effects of the various degrees of OP on these parameters. METHODS: Fifty six outpatient subjects were included in the study. All patients underwent a standardized interview, physical examination, bone mineral density (BMD), anteroposterior and lateral x-rays of thoracic spine, resting PF test and CPET evaluation. To evaluate the effects of the severity of osteoporosis on these parameters patient group divided according to diagnosis time of OP, degree of kyphosis, and spinal deformity index. Demographic and clinical data were compared between the groups with the use of independent-sample t test analysis (two groups) and analysis of variance (ANOVA) was used to estimate the between-group differences and changes by severity of osteoporosis and regression analyses to find predictors for changes. Correlation coefficients were used to examine the relationship between variables. RESULTS: According to diagnosis time, newly diagnosed groups; according to degree of kyphosis, the kyphotic groups; according to spinal deformity index, the higher spinal deformity index groups showed statistically significant and declining results in PF tests and CPET parameters. CONCLUSION: This study pointed out a significant impaired PF, aerobic capacity and a serious deconditioning for various reasons in these OP patients Therefore, the evaluation of CPET should be included in the management of OP patients and in these patients ventilatory muscle training and aerobic exercises may offer a potential therapeutic adjunct to current OP therapies in the future.

Changes in applicator positions and dose distribution between high dose rate brachytherapy fractions in cervix carcinoma patients receiving definitive radiotherapy.

This study examines the change of applicator geometry and its effect on rectal/rectum (R) and bladder (B) doses, and obtained radiobiological equivalent doses (RED), between each high dose rate (HDR) brachytherapy (BT) fraction in cervical carcinoma patients. BT using a tandem (T) and two ovoids (O) is included, and any discrepancies in applicator positions among the fractions were calculated. Whether the change of applicator position had an effect on the calculated R and B doses was analysed. Furthermore, the relationship between the size of tumour, the magnitude of displacement and the change in R and B doses was also investigated. Lastly, the changes in R and B RED were noted. The average magnitude of displacement was between 2.0 mm and 16.9 mm, showing time trend. There was no relationship between tumour size and the magnitude of discrepancy of Left O, Right O, T, R, B, and neither change in R and B doses (p>0.05). The mean differences of R and B doses were between 49-78 cGy, and 70-84 cGy, respectively. The magnitude of discrepancy and changes in doses showed no correlation (p>0.05). There were no significant differences in REDs for bladder (p = 0.8) and rectum (p = 0.2). In conclusion, there were significant differences in the applicator positions R and B and R and B doses among the fractions, which confirm the necessity of treatment planning in each HDR BT fraction. However, the total calculated R and B REDs did not show a remarkable difference.

The stability constants of copper(II) complexes with some alpha-amino acids in dioxan-water mixtures.

In this study, the overall stability constants of copper(II) complexes with some alpha-amino acids (glycine, dl-alanine, dl-valine, l-leucine, l-asparagine, l-glutamine) were determined by potentiometric titration in water, 25% dioxan-75% water, 35% dioxan-65% water, 50% dioxan-50% water, and 60% dioxan-40% water. The titrations were performed at 25 degrees C, under nitrogen atmosphere, and the ionic strength of the medium was maintained at 0.10 M by using sodium perchlorate. The formation curves of their complexes (n-p[L]) were obtained by means of the titration data. Then the stability constants were determined in relation to these curves. The mol ratio of copper(II) to alpha-amino acid was also determined and it was found that the complexes were CuL(2) type. Another important result obtained was that the tendency of amino acids to form complexes with copper(II) was greater in dioxan-water mixtures compared to water.

Studies on the protonation constants and solvation of alpha-amino acids in dioxan-water mixtures.

To gain more information about the effect of solvent on alpha-amino acids, the stoichiometric protonation constants of 10 alpha-amino acids (glycine, DL-alanine, DL-valine, L-leucine, L-isoleucine, DL-phenylalanine, L-serine, L-threonine, L-asparagine, and L-glutamine) in different dioxan-water mixtures have been determined potentiometrically using a combined pH electrode system calibrated in concentration units of hydrogen ion at 25 degrees C with an ionic strength of 0.10 M. For all amino acids studied, it was observed that the log K(1) values relating to the protonation equilibria of the anionic form are almost unaltered by the change in solvent composition. However, the log K(2) values corresponding to the formation equilibria of cationic form increase with the increase in dioxan content. The variation of these constants is discussed on the basis of specific solute-solvent interactions and structural changes of amino acids from water to dioxan-water media. The zwitterionic to neutral form ratio of these acids in dioxan-water mixtures is also discussed.

Microinvasive carcinoma of the cervix: an analysis of 31 patients.

A retrospective analysis of 31 patients subjected to radical surgery and lyphadenectomy for microinvasive cervical cancer was carried out. The mean age of the patients at diagnosis was 51.4 years. Twenty-nine of the patients had depth of invasion of 3 mm or less whereas 5 of them had lymphovascular space invasion. Thus, 24 patients had microinvasive cervical cancer according to the SGO (Society of Gynecologic Oncology) criteria. While nine patients had minimal stromal invasion (< 1 mm) at diagnosis, the remaining 22 patients fulfilled the criteria of FIGO IA2 disease. Most of the patients had grade I disease. With worsening of differentiation lymphovascular space involvement increases from approximately 11% (2/18) to 50% (1/2). None of the patients had lymph node involvement. All patients are living with no evidence of disease with a mean survival of 39 months. Current FIGO criteria for microinvasive carcinoma permits us to define a subset of patients that can safely be subjected to a more conservative approach.

The effects of a pulmonary rehabilitation program on pulmonary function tests and exercise tolerance in patients with Parkinson's disease.

The effects of exercise training, as a part of a pulmonary rehabilitation program, on pulmonary function tests and exercise tolerance have not been clarified in patients with Parkinson's disease (PD). This study compares the results of pulmonary function test parameters and exercise tolerance in individuals with and without PD. It also compares the results of pulmonary function test parameters, exercise tolerance and subjective ratings of perceived exertion (RPE) between entry to and the end of exercise training program in patients with PD. Nine patients with PD and 9 age-matched healthy controls participated in the study. Pulmonary function tests and a six-minute walk test were performed in subjects with and without PD, and the Borg RPE scale was applied to patients with PD at the beginning of the study. After the exercise training program, all parameters were recorded again in patients with PD. Statistically significant differences were observed between the groups in some of the pulmonary function test parameters and in exercise tolerance. After the training program, we observed improvement in some of the pulmonary function test parameters, exercise tolerance, and RPE in patients with PD.

Protonation constants of some substituted 2-hydroxy-1-naphthalideneanilines in dioxan-water mixtures.

The protonation constants of ten Schiff's bases synthesized by the condensation of 2-hydroxy-1-naphthaldehyde with aniline and o-, m-, and p-substituted methylanilines, ethylanilines and methoxyanilines in various dioxan-water mixtures have been determined potentiometrically using an electrode system calibrated in concentration units of the hydrogen ion. The influence of substituents in the molecular structure on the protonation constants is discussed. The log K(2) values relating to the protonation of imine nitrogen atoms are in accordance with the Hammett relationship for all solvent compositions. A reverse relationship is observed between log K(2) for all Schiff's bases and the mole fraction of dioxan. However, the log K(1) values corresponding to the protonation of naphtholate O-ions have been found to increase with the increase in concentration of dioxan. Both electrostatic and non-electrostatic contributions influencing these constants are briefly discussed.

Conductimetric titrimetry for assay of selected antibiotics in non-aqueous media.

In this study, a conductimetric titration method is proposed for the determination of some commonly used antibiotics. The conductimetric titration of three antibiotics, namely ampicillin, amoxycillin trihydrate and rifampin, was carried out in acetic acid using perchloric acid as titrant. Ciproflaxacin hydrochloride, however, was titrated after being dissolved in acetic acid containing an excess of mercury(II) acetate. For the titration of netilmicin sulphate, barium acetate prepared in acetic acid was used as titrant. The method was found to be highly accurate and precise, having a relative standard deviation of less than 1.0% for all antibiotics studied. It was also shown that the conductimetric titrimetry could be successfully applied to the assay of commercial preparations containing the above-mentioned antibiotics. The validity of the method was tested by the recovery studies of standard addition to pharmaceuticals and the results were found to be satisfactory.