bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose and schedule selection for the anti-CTLA4 monoclonal antibody ticilimumab in patients (pts) with metastatic melanoma
Authors: Gomez-Navarro J. , Sharma A. , Bozon V. , Bulanhagui C. , Pavlov D. , Eck S. , Ribas A. , Camacho L. H.
Published: April 2020

8032

Background: Ticilimumab therapy has demonstrated anti-tumor activity in pts with metastatic melanoma. Its indirect, immune-mediated antitumor effects pose unique challenges for dose/regimen selection. Methods: It was our original intention to select the clinical dose/regimen of ticilimumab based on (1) clinical safety and tolerability and (2) attainment of target plasma concentrations derived from pre-clinical work using an ex vivo assay of ticilimumab-induced enhancement of cytotoxic T-cell function. Because numerous pts with metastatic melanoma experienced clinical benefit (i.e., durable objective responses [OR] and/or long-term survival) in early clinical trials of ticilimumab, we are using (1) safety and tolerability and (2) clinical benefit to guide dose/regimen selection. Data for evaluating these criteria come from a single-dose Phase 1 trial (0.01, 0.1, 1, 3, 6, 10 and 15 mg/kg) and an ongoing multiple-dose Phase 1/2 trial in pts with melanoma (Phase 1 portion: 3, 6 and 10 mg/kg Q1M; Phase 2 portion: 10 mg/kg Q1M and 15 mg/kg Q3M). Results: In the single-dose Phase 1 trial, 10 mg/kg was the Protocol-defined MTD but a high rate of clinical benefit was seen in the 15 mg/kg dose cohort (6/6 pts). Because the DLTs seen at 15 mg/kg (Gr 3 diarrhea, Gr 3 rash) were moderate and resolved completely within 3 months of dosing, 15 mg/kg Q3M was proposed as a safe and tolerable dose and is being studied in the Phase 2 portion of the multiple-dose Phase 1/2 trial. The Phase 1 portion of the multiple-dose Phase 1/2 trial revealed that 10 mg/kg is safe and tolerable with monthly dosing so 10 mg/kg Q1M is also being studied in the Phase 2 portion of the trial. At the end of the Simon Optimum-defined Stage 1 of the Phase 2 portion of the ongoing trial, the OR rate (3/18 pts) is the same for both dosing regimens. However, with 15 mg/kg Q3M, Gr 3/4 adverse events were less frequent (6% versus 34%). Conclusions: 15 mg/kg Q3M is proposed as the clinical dose/regimen for ticilimumab in metastatic melanoma. This dose/regimen appears to have anti-tumor activity approximately equal to 10 mg/kg Q1M but it appears to have a superior safety profile.

[Table: see text]
Chemotherapy-naïve cancer patients’ expectations of developing treatment-related side effects: A URCC CCOP study of 670 patients from community practices
Authors: Hofman M. , Morrow G. R. , Ranson S. L. , Jean-Pierre P. , Dakhil S. R. , Moore T. , Atkins J.
Published: April 2020

8509

Background: Adequate management of cancer related side effects is important for patients yet challenging for clinical staff. Cancer treatment side effects have been characterized reasonably well in the literature; however, less is known about the relationships among response expectancies, personal characteristics, and side effects development of chemotherapy-naïve patients undergoing doxorubicin treatments. Methods: The present sample included 701 cancer patients from 14 CCOP institutions affiliated with the URCC CCOP research base. Of the total sample, 670 patients provided evaluable data to an item that assessed expectations that they will develop side effects such as nausea, vomiting, fatigue, and hair loss. Patients indicated their expectations on a 5-point scale (from 1 = “I am certain I will NOT have this” to 5 = “I am certain I WILL have this”). Results: The median number of symptoms expected (any value other than 1) was 4. Hair loss was most expected (98%) and vomiting the least (87%). Older patients (> 53-years, N = 316, ) were less confident they would get nausea (Mold = 2.96, SE = 0.064; Myoung = 3.23, SE = 0.057, p < 0.01) and hair loss (Mold = 4.22, SD = 0.063; Myoung = 4.39, SE = 0.051, p < 0.05). Females (n = 633) were more confident they would get hair loss than males (Mfemale = 4.34, SE = 0.041; Mmale = 3.89, SE = 0.172, p < 0.05). Patients who had some college (n = 397) thought it was more likely they would get hair loss than patients with less education (Mcollege = 4.38, SE = 0.048; Mnocollege = 4.21, SE = 0.069, p < 0.05). Conclusions: Chemotherapy-naïve patients scheduled to take doxorubicin clearly exhibit expectations about treatment side effects, which are influenced by age, gender and education. The findings show that knowledge of patients’ response expectancies and personal characteristics should be considered and integrated into interventions to control treatment side effects. Supported, in part, by a supplement from the Division of Cancer Control and Population Sciences, NCI, to Public Health Service grant U10 CA37420 and by grant RSG-01-071-PBP from the ACS

[Table: see text]

No significant financial relationships to disclose.
Perceptions and beliefs related to cancer care among African-American and Caucasian patients
Authors: Matsuyama R. K. , Lyckholm L. J. , Grange C. , Utsey S. , Smith T. J.
Published: April 2020

8518

Background: Without a clear understanding of belief systems and cultures it is not possible to provide optimal care to ethnic minority individuals. This study examined perceptions and beliefs of African-Americans and Caucasians related to cancer care. Methods: Eleven focus groups were conducted with 39 African-American and Caucasian cancer patients recruited from a university-affiliated cancer clinic, using established qualitative methodology. Data analysis included whole group analysis with a team of 4 researchers. Atlas Ti software was used to validate the coding and establish Intra-rater and inter-rater reliability. Results: There were consistent themes across both ethnicities that related to reactions to diagnosis, wanting certain types of information, wanting to stay positive, coping, and social connectivity. Cultural differences were also apparent (Table). Differences based on ethnicity Conclusions: African-American participants described increased religiosity and faith after diagnosis and were more likely than Caucasian participants to seek information about cancer issues from friends, family, and community. There also were differences in perceptions of how health care providers demonstrate care for patients. Findings have implications for training professionals regarding ways patients seek information, the role of spirituality and religion in care and behaviors that patients perceive as indicative of caring.

[Table: see text]

No significant financial relationships to disclose.
Polysomnographic measures of sleep moderate the relationship between depression and pain
Authors: Parker K. P. , Bliwise D. L. , Dalton J. , Harris W. , Jain S. , Kohles-Baker M. , Ribeiro M. , Vena C. , Viswanathan B.
Published: April 2020

8526

Background: We explored the effects of polysomnographic measures of nocturnal sleep on depression and pain in advanced cancer patients taking opioids. Methods: The sample included 72 subjects (solid tumor, Stages III/IV) with a mean age of 55.9 (9.1); 39 were male. All were taking opioids. Subjects underwent ambulatory polysomnography for 48 hours in their homes. Nocturnal sleep parameters included total sleep time (minutes); sleep efficiency (SE; %); sleep latency (SL; minutes); rapid-eye-movement sleep latency (REML; minutes); the percentages (%) of non-rapid eye movement (NREM) Stages 1, 2, and slow wave sleep (SWS, 3 & 4), and REM sleep; and the number of awakenings > 60 seconds. Subjects kept an opioid diary, data from which were converted into a mean hourly morphine equivalent dose (HMED). Subjects also completed the Brief Pain Inventory (BPI) and the Beck Depression Inventory (BDI). Descriptive, correlation, and regression procedures were used for data analysis. Results: Subjects had a mean nocturnal sleep period of 400.1 ± 97.4 minutes. The SL was normal at 26.5 ± 42.6 minutes but the SE was low (77.5 ± 13.2%). Most sleep was light NREM Stages 1 and 2 with decreased amounts of deep SWS (0.3 ± 2.7%) and REM sleep (14.4 ± 8.5%). The REML was prolonged at 149.1 ± 105.1 minutes. The mean BPI scores for pain intensity and interference were 4.4 ± 1.4 and 5.0 ± 2.1, respectively. The mean BDI score was 13.7 ± 7.9. The average HMED was .59 ± .1. Controlling for age and gender, regression analyses revealed that SWS and REM sleep moderated the relationship between depression and pain. Those with more SWS had lower depression levels in spite of higher pain intensity (t = -2.8, p = .007) while those with more REM sleep had lower depression levels despite higher pain interference (t = -2.0, p = .045). Controlling for pain intensity and interference, HMED was positively associated with Stage 1 % (r = .36, p = .001) and the number of nocturnal awakenings > 60 seconds (r = .28, p = .019). Conclusions: Opioids may lighten and disrupt sleep altering sleep cycle progression. The resulting decrements in SWS and REM sleep may lead to increased depression and enhanced pain. Consideration of the timing and dosing of opioids in relationship to nocturnal sleep may decrease depression and subsequently optimize pain management.

No significant financial relationships to disclose.
Can preoperative assessment of cancer in the elderly (PACE) predict 30-days postoperative outcomes?
Authors: Audisio R. A. , Ramesh H. S. , Gennari R. , Corsini G. , Maffezzini M. , Hoekstra H. J. , Mobarak D. , Bozzetti F. , Colledan M. , Wildiers H. , Pope D. P.
Published: April 2020

8537

Background: Surgery is the treatment of choice for solid cancers. Frequent functional impairment/comorbidities in the elderly enhances the risk of treatment related complications. Inability to forecast short term outcomes after cancer surgery in elderly affects clinical practice, denying optimal treatment. No validated instrument is available to help make informed decision; a compilation of validated questionnaires (PACE) is established to preoperatively inform on the health condition of elderly cancer pts. This international multicentre study investigates how components of PACE preoperatively assessed are associated with postoperative outcomes. Methods: A prospective series of consenting elderly cancer pts (≥70 yrs) receiving elective surgery (moderate-major+) were recruited from 8 hospitals (UK, Netherlands, Italy, Japan, Belgium) (07/2003–12/2005) and assessed using PACE (Comorbidities, IADL, ADL, GDS, BFI, PS, MMS, ASA). 30day morbidity, hospital stay and mortality were recorded. Results: 448 pts [breast (48%), GI (30%), GU (16%), miscellaneous (6%)] were recruited and followed postoperatively. Observed morbidity was 36% (161 pts), mortality 4% (16 pts) and median hospital stay was 5 days (range 2 -10). All components of PACE but ASA were associated with morbidity (p<0.05) and hospital stay (p<0.05) on univariate analysis. Operative deaths were too few to look for associations. Forward stepwise logistic regression models (multivariate analysis) identified 3 components of PACE as best describing the occurrence of post-surgical morbidity: BFI (OR (upper quartile)= 2.4; 95% CI=1.2–4.9); PS (OR=1.9; 95% CI=1.1–3.4); IADL (OR=1.7; 95% CI=1.0–3.0). The same components were also selected into the model as best describing hospital stay beyond average: BFI (OR (upper quartile)=18.1; 95% CI=7.2–45.3), PS (OR=2.2; 95%=1.2–4.4) and IADL (OR=2.7; 95% CI=1.4–5.1). Of those pts exposed to all 3 factors entered into the regression models 61% experienced complications and >80% had a longer hospital stay. Conclusions: BFI, PS and IADL appear to be the most relevant prognosticators of short term surgical outcomes. A holistic appraisal of elderly pts undergoing surgery is warmly recommended when consenting the patient and during the decision making process.

No significant financial relationships to disclose.
Effect of zoledronic acid (Z) treatment based on serum parathyroid hormone (PTH) levels in patients (pts) with malignant bone disease
Authors: Berruti A. , Dogliotti L. , Tampellini M. , Lipton A. , Hirsh V. , Saad F. , Liati P. , Shirina N. , Cook R. , Hei Y. L.
Published: April 2020

8610

Background: Z prevents skeletal-related events (SREs) in pts with bone metastases or multiple myeloma. However, secondary hyperparathyroidism and increased PTH may stimulate osteoclast activity and tumor growth, thus potentially limiting the efficacy of Z. Methods: Serum PTH was assessed at baseline and every 3 months in 1,068 pts enrolled in 3 randomized trials: 547 received Z, and 521 received placebo or pamidronate. Results: 213 (20%) pts had elevated PTH at baseline, and 105 of 547 (19%) pts had elevated PTH during Z treatment. In patients with normal baseline PTH, Z significantly reduced the incidence of SREs and delayed time to first SRE compared with control, whereas the risk of SREs was not reduced in patients with elevated baseline PTH. In prostate cancer patients, Z significantly decreased the risk of death compared with placebo in pts with normal baseline PTH (relative risk [RR] = 0.72; 95% confidence interval [CI]: 0.55, 0.94; P = .015). No survival advantage was observed in this subpopulation among pts with lung cancer or other solid tumors. In the small subset of pts with elevated PTH during Z treatment, there was an increased risk of death (for breast cancer pts, RR = 1.68 [95% CI: 1.10, 2.56]; P = .016; for prostate cancer pts, RR = 2.92 [95% CI: 1.83, 4.67]; P < .001). Additionally, elevated PTH during Z treatment in prostate cancer pts also significantly correlated with an increased risk of bone lesion progression (RR = 1.54 [95% CI: 1.09, 2.17]; P = .015). Elevated PTH during treatment did not affect the incidence or time to onset of SREs. Among pts with lung cancer or other solid tumors, elevated PTH during Z treatment did not provide any predictive or prognostic information. Conclusions: PTH levels either at baseline or during Z treatment appear to correlate with disease progression and the clinical benefit of Z in pts with bone metastases from certain types of cancer. This retrospective analysis suggests the importance of PTH status in patients undergoing Z treatment. Normalization of PTH levels may increase the benefit of Z.

[Table: see text]
ELYPSE 2: A prospective randomized trial comparing filgrastim (G-CSF) in primary and secondary prophylaxis in patients (pts) at high risk for febrile neutropenia (FN)
Authors: Biron P. , Ray-Coquard I. , Le Cesne A. , Dussart S. , Goilliot C. , Bachelot T. , Thyss A. , Gilles E. , Chabaud S. , Blay J.
Published: April 2020

8614

Background: FN is a frequent life-threatening consequence of cytotoxic chemotherapy (CT). G-CSF reduces the risk of FN, but primary (1ry) prophylaxis using G-CSF may be cost efficient only if FN incidence is ≥20%. The identification of pts at high risk for FN with simple criterias would be useful in clinical practice. Here we report a randomized phase II trial comparing G-CSF in 1ry vs 2ry prophylaxis in a high risk group of pts (based on our risk model JCO 1996;14:737, Br J Cancer 2003;88:181). Methods: Pts ≥18 years with solid tumors or NHL at high risk for FN after CT were incluable: these were pts with day 1 or day 5 lymphocytes (Ly) count ≤700/μL AND “high risk CT” (HRCT) In pts with d1 and d5 Ly ≤700/μL, the observed incidence of FN was 40% and 66% respectively G-CSF (300 to 480μg/d from d6–12) was randomized either as in 1ry prophylaxis (Arm 1), or as 2ry prophylaxis after FN (Arm 2). Primary endpoint was the rate of grade 4 FN. Hypothesis was a reduction of 40% of the risk of FN with 1ry prophylaxis. Results: Between 03/97 and 12/04, 137 pts were included in 7 centers. The median age was 53 years (range 18–80) with 54% males. Most frequent tumors were sarcomas (36%), breast carcinomas (18%), lymphomas (15%), head and neck carcinomas (10%), and lung carcinomas (6%). 23% patients had PS>1 at the first line of chemotherapy. No difference was observed in terms of duration of hospitalization or antibiotherapy. Median number of days of G-CSF administration was 14 days (0–24) vs 0 (0–17) days (p<0.0000). After the 1st course, grade 4 FN was 38% in Arm 2 (2ry prophylaxis) and 25% in Arm 1 (1ry prophylaxis), showing a 34% reduction of FN in arm 1 (p=0.14): 1ry prophylaxis was associated with a significant reduction of FN using logistic regression (p=0.04). Incidence of FN after the 2 course in pts receiving 2ry prophylaxis was 22%. Among the subgroup of pts with PS>2 and Ly ≤700/μL, (a group with a reported 20% risk for early death, Br J Cancer 2001;85:816), 2 of 8 patients (25%) died after the 1st course, vs 0/13 in the G-CSF group (p=0.05). This difference was not significant in the whole group. Conclusions: This study confirms that lymphopenic pts receiving HRCT are a high risk group of pts for FN for whom 1ry prophylaxis with G-CSF reduces the incidence of FN.

[Table: see text]
Ondansetron oral spray (Zensana) versus ondansetron oral tablets in a randomized, bioavailability study in adult subjects
Authors: Yates W. , Berk G. I. , Wolter M. , Nino S. , Kollipara S. , Chavira R. , Kisicki J.
Published: April 2020

8622

Background: Zensana ondansetron oral spray (ZSN) is the first oral spray 5-HT3 antagonist to deliver ondansetron, the most commonly prescribed anti-emetic for chemotherapy induced nausea and vomiting (CINV) through the oral cavity. ZSN achieves therapeutic drug levels by delivering small droplets of concentrated drug solution over the oral mucosa, which has a rich blood supply and has been shown to be an alternative drug delivery route. ZSN may offer certain advantages to patients experiencing CINV who have difficulty swallowing and holding down pills. Methods: This was a randomized, crossover, pharmacokinetic (PK) study where ZSN, administered as 4mg, 8mg, 12mg, and 8mg with a 30-sec hold before swallowing was evaluated in healthy subjects against an 8mg ondasetron (Zofran [ZFR]) tablet (reference). Treatments were separated by 48 hrs. PK samples were measured during the 24 hrs after dosing and were assayed using LC/MS/MS techniques. PK parameters were analyzed using a cross-over ANOVA model. Two treatments were concluded bioequivalent if the 90% CI of the geometric mean ratios for ln-transformed Cmax, AUC0-t, and AUC0-inf fell between the FDA guideline of 80% to 125%. Results: Thirty-two subjects (17 women, 15 men) received each of the 5 treatments, except for one man who did not receive the 12mg dose. The geometric mean ratios and the 90% CI for Cmax, AUC0-t, and AUC0-inf respectively, for each pair of treatments were as follows: ZSN 4mg vs 8mg tablet (TAB): 41%(39–43%); 45%(43–47%), and 47%(45–49%); ZSN 8mg vs 8mg TAB: 87%(83–91%), 98%(94–102%), and 99%(94–103%); ZSN 12mg vs 8mg TAB: 145%(138–152%), 157%(150–164%), and 157%(150–164%); and ZSN 8mg with a 30 sec hold vs 8mg TAB: 86%(82–90%), 99%(94–103%), and 99%(95–104%). There were no serious or unexpected adverse events (AE) and the safety profile was similar across all treatments. The most commonly reported AEs were constipation (11/32[34%]), headache (10/32[31%]), and dizziness (5/32[16%]) which were mild to moderate in severity. Conclusions: ZSN 8mg falls within the FDA criteria for bioequivalence, and is bioequivalent to an 8mg ZFR tablet. ZSN 4, 8, or 12mg has a similar safety profile as a ZFR 8 mg tablet.

[Table: see text]
Incidence of venous thromboembolic (VTE) in chronic lymphocytic leukemia (CLL) patients (pts) treated with immunomodulating agents (IMiDs)
Authors: Depaolo D. , Miller K. , Musial L. , Marshall P. , Coignet J. , Padmanabhan S. , Chanan-Khan A. A.
Published: April 2020

8625

Introduction: We recently reported the clinical activity of IMiDs (both thalidomide (T) and lenalidomide (L)) in pts with CLL. VTE is a commonly reported complication of these agents requiring prophylaxis. Most available information is in pts treated for multiple myeloma (MM), a disease with a high baseline incidence of VTE. To determine whether the incidence of IMiDs associated VTE is similar in CLL pts we reviewed all CLL pts treated with IMiDs at our institute. Method: All CLL pts treated at our institute with T or L either alone or in combination with other antileukemic agents such as rituximab (R) or fludarabine (F)) were evaluable for this analysis. All pts were treated on IRB approved clinical trials and signed informed consent. Prophylaxis for VTE was recorded. Dose range for T was 100–300mg/day, while that of L was 5–25mg/day. Results: To date a total of 55 pts (35 on L and 20 on T) are treated with IMiDs at our center. All pts treated with L received single agent L while those treated with T received concurrent F (FT). All T treated pts also received low-dose warfarin (1 or 2 mg for body weight ≤ or > than 70 kg respectively) for VTE prophylaxis. No prophylaxis was given to L treated pts. VTE was noted in 2 (6%) pts on L and 2 (10%) on FT. Thus the cumulative incidence of IMiDs associated VTE in CLL pts at our center was 7% (4/55). Conclusion: VTE is a known side effect of IMiDs. Its incidence in CLL treated pts is unknown. Our experience with both T and L in CLL pts suggest that VTE remains a concern in this pt population as well though the incidence may be lower. Three other studies investigated T either alone (n=28)1, with F (n=18)2 or with dexamethasone/cyclophosphamide (n=3)3. Only 1 episode of VTE was reported in these studies.3 Our current analysis failed to reveal any apparent risk factors for VTE in CLL pts treated with IMiDs. Several pts on the L clinical trial continue to be on therapy. Updated results with prolonged L treatment will be presented at the meeting. 1. Kay N et al: ASH 2003 2. Furman RR et al: ASCO 2005 3. Trompeter S et al: IWCLL 2005

[Table: see text]
Cognitive dysfunction, brain-derived neurotrophic factor and IL-6 levels in cancer patients with depression
Authors: Jehn C. F. , Becker B. , Pfeiffer S. , Krebs M. , Possinger K. , Flath B. , Dieing A.
Published: April 2020

8632

Background: Increased proinflammatory cytokines (IL-6) and decreased brain-derived neurotrophic factor (BDNF) levels have been implicated in the pathophysiology of depression. Depression has been shown to be associated with cognitive dysfunction. The objective of this study was to assess the correlations between cognitive dysfunction, IL-6 and BDNF in cancer patients (pts) with depression. Methods: Depression was assessed in 55 patients with metastatic cancer by the Hospital Anxiety and Depression Scale (HADS) and diagnosis was established according to DSM-IV criteria. Cognitive function was assessed by the Auditory Verbal Learning Test (AVLT). Plasma concentrations of Interleukin-6 and BDNF were measured at 8 AM the same day. In the statistical analysis the Mann-Whitney test and the Pearson correlation were applied. Results: Pts characteristics (n=55): median age 60 y (25–85); 76.9% Females, 23.1% males. 52% of pts had depression. There were no significant differences in mean age or Karnofsky-index between pts with and without depression. Depression was associated with a significant higher median IL-6 level (14.8 vs. 3.7 pg/ml; p<0,001). For Cognitive function only the longterm memory was significantly reduced in depression (p=0.01). However, there was no difference in BDNF levels between both groups (p=0.164). There were correlations between HADS-D score and IL6 (r=4.11; p=0.002), IL-6 and BDNF (r= −0.42; p=0.001), BDNF and longterm memory (r=0.48; p=0.02). No correlations were found for level of depression (HADS-D score) and BDNF levels (r= −0.20; P=0.14). Conclusions: Depression and increased plasma IL-6 concentrations are strongly associated in pts with cancer. There seems to be no association between BDNF and depression in cancer pts. However there is a positive correlation between the cognitive function, at least for longterm memory, with BDNF.

No significant financial relationships to disclose.
False Consciousness for Liberals, Part I: Consent, Autonomy, and Adaptive Preferences
Authors: Enoch David
Published: April 2020

The starting point regarding consent has to be that it is both extremely important, and that it is often suspicious. In this article, the author tries to make sense of both of these claims, from a largely liberal perspective, tying consent, predictably, to the value of autonomy and distinguishing between autonomy as sovereignty and autonomy as nonalienation. The author then discusses adaptive preferences, claiming that they suffer from a rationality flaw (they are typically formed for reasons of the wrong kind) but that it's not clear that this flaw matters morally or politically. What matters is whether they suffer from an autonomy flaw. To answer this question, the author develops an account of autonomy failure, according to which a preference is nonautonomous if an injustice played an appropriate role in its causal history. The author then discusses the moral implications—and in an initial way, the political ones as well—of proclaiming a preference, or consent based on it, nonautonomous in this way.
Relationship of C-peptide levels to duration of Type 1 diabetes – A study from Sindh, Pakistan
Authors: Fawwad Asher , Waris Nazish , Askari Saima , Ogle Graham , Ahmedani Muhammad Yakoob , Basit Abdul
Published: April 2020

Objective: To determine the relationship of C-peptide levels with duration of type 1 diabetes mellitus.

Methods: This prospective study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University (BMU), Karachi-Pakistan from December 2013 to December 2015. A total of 184 subjects were recruited during the study period, 100 in Group-A and 84 in Group-B. Subjects clinically diagnosed with type 1 diabetes Mellitus (T1DM) were categorized into two groups based on duration of diabetes: Group-A (with ≤1-year duration of diabetes) and Group-B (with >1-year duration of diabetes). Ninety-nine of the 100 enrolled subjects in Group-A were diagnosed as having T1DM, with one subject who presented at 11.9 years of age and diagnosed with T2DM excluded from this study. Blood samples were drawn for biochemical parameters. Data for baseline characteristics and clinical parameters (HbA1c and C-peptide) were obtained from hospital management system of BIDE.

Results: Fifty-seven (57.6%) subjects in Group-A, and 39 (46.4%) in Group-B were males. Mean±SD duration of diabetes (years) was 0.64±0.6 (range 0-1) in Group-A, and 7.65±5.5 (range 1-23) in Group-B. Family history of T1DM and T2DM was 1(1%) and 27(27.3%) in Group-A, and 8(9.52%) and 21(25%) in Group-B, respectively. Twenty-one (21.2%) subjects presented in diabetic ketoacidosis (DKA) in Group-A and 18(21.4%), in Group-B. Mean±SD for HbA1c was non-significantly higher in Group-A 11.12±2.31 compared to Group-B 10.42±1.45. Mean±SD for C-peptide was 1.91±1.53 ng/mL (0.60±0.481 nmol/L) in Group-A, and 1.82±1.01 (0.57±0.32 nmol/L) in Group-B (p=0.984).

Conclusion: The study found that subjects with longer duration of T1DM had non-significantly decreased C-peptide levels compared to a group in which C-peptide was measured at or soon after diagnosis. Furthermore, C-peptide levels in many subjects with longer duration were higher than expected in classic T1DM.

doi: https://doi.org/10.12669/pjms.36.4.1531

How to cite this:Fawwad A, Waris N, Askari S, Ogle G, Ahmedani MY, Basit A. Relationship of C-peptide levels to duration of Type 1 diabetes – A study from Sindh, Pakistan. Pak J Med Sci. 2020;36(4):765-769. doi: https://doi.org/10.12669/pjms.36.4.1531

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Mechanical properties of an experimental resin based composite containing silver nanoparticles and bioactive glass
Authors: Hanif Amjad , Ghani Fazal
Published: April 2020

Objective: To compare the elastic modulus, flexural strength, and hardness of an experimental resin based composite (RBC) with and without containing silver nanoparticles (AgNPs) and bioactive glass (BAG) with a commercially available RBC.

Methods: This study was conducted, during the period August 2016-May 2018, at the Department of Dental Materials, Peshawar Dental College, Peshawar (Pakistan) and Department of Chemistry, University of Montreal, Canada. Test specimens made in the commercial RBC acted as Group-1 (G1). An experimental RBC containing 70 wt % filler content was synthesized. It was first used as such to prepare test specimens to act as the experimental control group (G2). This RBC was then modified by adding various amounts of BAG (5%, 10% and 15%) and a fixed amount of 0.009% AgNPs to use the so modified RBCs for preparing the test specimens to belong to three groups (G3, G4 & G5). The AgNPs had been synthesized in situ by reduction of salt during photo-polymerization. Flexural strength (FS), elastic modulus (EM) and Vickers hardness were determined using universal testing machine and hardness tester respectively. Data were analyzed using one-way ANOVA and Tukey post-hoc test.

Results: Except for G3 restorations showing significantly lower mean FS value, the FS for those in the other groups were not significantly different (p>0.05). Elastic modulus of the experimental RBC restorations was though higher than those of the others but the difference was statistically insignificant (p>0.05). Reduced Vickers hardness values were documented for the restorations in the G4 and G5 compared to those in the G3 but again the difference was insignificant (p>0.05). Flexural strength and hardness values of the test specimens in the experimental RBCs were significantly lower than those made in the commercial hybrid RBC (p<0.05).

Conclusion: BAG and AgNPs addition to the experimental RBC in the mentioned concentration adversely affected the tested mechanical properties.

doi: https://doi.org/10.12669/pjms.36.4.1913

How to cite this:Hanif A, Ghani F. Mechanical properties of an experimental resin based composite containing silver nanoparticles and bioactive glass. Pak J Med Sci. 2020;36(4):776-781. doi: https://doi.org/10.12669/pjms.36.4.1913

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Leishmaniasis in Saudi Arabia: Current situation and future perspectives
Authors: Abass Elfadil , Al-Hashem Zainab , Yamani Lamya Zohair
Published: April 2020

Background and Objective: Leishmaniasis is endemic in Saudi Arabia with cases reported in many regions. This review refers to publications on leishmaniasis in Saudi Arabia and discusses issues related to parasite species, clinical manifestation and diagnosis.

Methods: This research was done at Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia by systematic literature search on PubMed and Google Scholar databases from 1989 to 2018. Selection criteria included original articles reporting on visceral leishmaniasis (VL) or cutaneous leishmaniasis (CL) in Saudi Arabia.

Results: The search identified 16 eligible articles, six for VL and 10 for CL. VL was reported in areas known to be non-endemic. Leishmania donovani was the main cause for human VL while Leishmania infantum seemed to cause the disease in animals. Dogs were considered the main reservoir hosts and black rats (Rattus rattus) were potential hosts. VL mainly affected infants and young children. It is important to note that VL diagnosis was based on either invasive parasite detection procedures or serologically using indirect hemagglutination test. CL represented the most frequent clinical form with the main endemic foci reported in the South-West and Eastern regions. CL appeared to have no demographic or socioeconomic restriction; it affected both rural and urban citizens, with the majority occurring among farmers. Travelling was recognized as an important risk factor. Leishmania tropica and Leishmania major were recognized as the main causes for CL.

Conclusion: This report summarizes the potential risks for VL and CL in Saudi Arabia in areas known to be non-endemic. There are substantial gaps in knowledge and practices in regard to leishmaniasis in Saudi Arabia, highlighting the need for more research and medical surveillance targeting the disease in humans and animals.

doi: https://doi.org/10.12669/pjms.36.4.2121

How to cite this:Abass E, Al-Hashem Z, Yamani LZ. Leishmaniasis in Saudi Arabia: Current situation and future perspectives. Pak J Med Sci. 2020;36(4):836-842. doi: https://doi.org/10.12669/pjms.36.4.2121

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Prevalence and new histopathological aspects of Haemoproteus spp. in pigeons from Iran
Authors: BAHRAMI S. , ESMAEILZADEH S. , ALBORZI A. R. , NIKNEJAD S.
Published: April 2020

Haemoproteus spp. is pathogenic protozoan that effecting blood circulatory system of birds. The present study was undertaken to evaluate the presence of Haemoproteus spp. in pigeons from Iran and associatedhistopathological changes. A total of 108 blood samples were taken from pigeons to investigate Haemoproteus spp. presence by blood smear and semi-nested PCR targeting the cytochrome b gene methods. Also, to evaluate histopathological changes 12 infected pigeons to Haemoproteus were sacrificed and studied. 34.2% of pigeons infected with Haemoproteus showed macro and microgametocytes in their erythrocytes while based on the molecular method 63.8% were infected. Focal lymphocytic aggregates, pigmentation and cell swelling were the main histopathological lesions in infected livers. Multifocal non- suppurative interstitial nephritis, pigmentation and splenic lymphoid hyperplasia were also seen in the infected pigeons. Mild lymphocytic myocarditis in the heart of one pigeon was the other finding. No histopathological changes were seen in brain, intestine, and pancreas. Schizonts with variable shapes and sizes were detected in infected livers, lungs, kidneys, and spleens but megaloschizonts were not found. This study also reports the molecular prevalence of Haemoproteus spp. in Iran
The Effect of Capsaicin on IGF-I and IGF-IR Expression in Ovarian Granulosa Cells
Authors: GULER S. , ZIK Β.
Published: April 2020

Capsaicin (trans-8-methyl-N-vanillyl-6-noneadamide) is a pungent ingredient in red peppers from the Capsicum family. Insulin-like growth factor-I (IGF-I) is expressed in granulosa cells and has an important role in ovarian development. However, there are no data about the IGF-I expression in ovarian granulosa cells after capsaicin treatment. The aim of this study was to investigate the expression of IGF-I and its receptor (insulin-like growth factor-I receptor [IGF-IR]) in primary rat ovarian granulosa cells after low and high doses of capsaicin treatment. For this, granulosa cells were isolated and cultured from ovaries of 30-day-old female Sprague-Dawley rats. Granulosa cell plates were divided into four groups as cell control (C), vehicle control (V), and 50 μM and 150 μM capsaicin groups. In experimental groups, granulosa cells were exposed to capsaicin for 24 hours and immunocytochemistry was performed afterwards using anti-IGF-I and anti-IGF-IR antibodies. Both IGF-I and IGF-IR expressions were found to be significantly increased in parallel to the capsaicin doses. Elevated levels of IGF-I may be a risk factor for ovarian development. Because of the crucial role of IGF-I in ovary development, capsaicin treatment can be effective on follicular development and/or disorders characterized by high IGF-I levels.
Clinical signs, aetiology and outcome in 30 cats with recurrent seizures (2002-2018)
Authors: KALOGIANNI L. , BAKA R. D. , POLIZOPOULOU Z. S.
Published: April 2020

The purpose of the current study was to describe seizure types, aetiology, treatment response and outcome in 30cats with recurrent seizures. This retrospective case series study included the medical records of client-owned cats, admitted to the Clinic of Companion Animals for seizure disorders, from 2002 to 2018. Recorded data included history, seizure type, physical and neurological examination findings, blood pressure measurements, complete blood counts, serum biochemistry profile and urinalysis, tentative/final diagnosis, treatment, hospitalization and longterm outcome. A total of 298 feline neurology cases were examined during the study period. Of those, 38 cases were admitted for seizure disorders and 30 met the inclusion criteria. Median age on admission was 38,2 months (3,1 years) (range 2 months- 14 years old).Seizure types, as per owner description, were generalized (26 cats), focal with secondary generalization (3 cats), focal (2 cats) and complex (1 cat). Cluster seizures appeared at least once in 18/30 and status epilepticus in 7/30. Different seizure types were also recorded in individual cases. Fifteen cats (15/30) were hospitalized at least once and the duration of hospitalization ranged from 1-10 days. In most cases, in which diagnosis was established, epilepsy wassecondary (25/30), due to previous head trauma(11/30),metabolic (1/30), or inflammatory (4/30) disease, arterial hypertension (3/30), toxicosis (3/30) and intracranial neoplasia (2/30).Congenital hydrocephalus was detected in 1 cat. Tentative diagnosis could not be established in 5cats; however differential diagnosis included inflammatory or neoplastic encephalopathies.Antiepileptic drug monotherapy (phenobarbital or levetiracetam) was sufficient to control the seizures in 14 cases, while administration of combination therapy with 2 or more antiepileptic drugs was required in 5 cases (phenobarbital, levetiracetam, gabapentin). Successful control was achieved in 11/30 animals for 1-5 years. Seven cats required intensive care at least once due to status epilepticus. Until today, eighteen (18/30) cats are still alive and 11 died or were euthanized.Although in most cases epilepsy was secondary, seizure control was adequate and quality of life (QoL) was improved with antiepileptic drugs when metabolic, inflammatory and neoplastic encephalopathies were excluded.
Health Risks associated with residual pesticide levels in fish reared in purified wastewater from slaughterhouse
Authors: PELIĆ M. , KARTALOVIĆ B. , ŽIVKOV BALOŠ M. , MIRILOVIĆ M. , ĐORĐEVIĆ M. , TEODOROVIĆ V. , ĆIRKOVIĆ M. , LJUBOJEVIĆ PELIĆ D.
Published: April 2020

The main objective of the present research was to determine the concentrations of the selected pesticides in muscle, liver and skin of common carp. Fish were sampled in two different seasons from fish pond which received previously treated slaughterhouse wastewater. Pesticides including etridiazole, chloroneb, trifluralin, propachlor, chlorothalonil, hexa-chlorocyclopentadiene, atrazine, simazine, alachlor, metribuzin, metolachlor, DCPA, cyanazine, chlorobenzilate, endrin aldehyde, cis permethrin and trans permethrin were determined by using a GS-MS method. Many of pesticides were not determined or determined in low concentrations. Propachlor was found in muscle, skin and liver. The recommended acceptable daily intake was higher in comparison with the estimated daily intake for examined pesticides via fish reared in treated slaughterhouse wastewater. It is very important to maintain the safety of the fresh fish produced in wastewater in order to ensure food safety and avoid health problems in humans.
A study of Neospora caninum antibody seroprevalence ın dairy cows in Turkey
Authors: KASAP S. , ERTUNC S. , TEMIZEL E. M. , SENTURK S.
Published: April 2020

Neospora caninum is a intracellular protozoan parasite and is one of the major causes of repeated abortions, foetal malformations, pre-term deliveries, stillbirth and possible loss of milk yield in livestock. The presence of specific antibodies against N. caninum in the blood serum of dairy cows is investigated in the present study. A total of 184 blood serum samples of dairy cows were examined in Bursa province in the Marmara Region. N. caninum antibodies were measured using an indirect enzyme-linked immunosorbent assay (ELISA) (The Svanovir Neospora-Ab ELISA). From the total sample, antibodies to N. caninum were detected in 62 of the 184 examined cows (33.3%) and neurological findings were seen in a calf.
Genetic characterization of Lactococcus garvieae isolated from farmed rainbow trout by random amplified polymorphic DNA-PCR in Iran
Authors: FADAEIFARD F. , RABIEI M. , SHARIFPOUR M. F.
Published: April 2020

Lactococcosis is one of the main bacterial infections of fish around the world. Lactococcus garvieae has been a major cause of rainbow trout losses in freshwater farming. This study aimed to genotype and determine the variability of L. garvieae isolated from infected farmed rainbow trout in Iran by the RAPD-PCR method. Bacterial samples were collected from 12 farms located in the western part of Iran and suspected to carry Lactococcus infection. Two hundred bacterial cultures containing cocci shaped bacteria were cultured in Trypticase soy agar (TSA) and blood agar mediums. All bacterial cultures were tested by conventional microbiological and biochemical tests, and PCR assay to identify L. garvieae by 16S rDNA genes. The RAPD-PCR method was used to determine the genetic pattern of all isolates. The sample strain pattern of the isolates was analyzed in the NTSYS program. According to a similarity coefficient index of 70%, all L. garvieae isolates were separated into two groups with four RAPD profile types. The highest and the lowest genetic pairwise similarity among the isolates were 98% and 54%, respectively. The results of the present study revealed that RAPD-PCR is an applicable method to describe the genetic diversity of different strains of L .garvieae among farmed fish.
Whole issue
Authors: Εταιρεία Ελληνική Κτηνιατρική
Published: April 2020

NO ABSTRACT AVAILABLE
Effects of standard diets from different sources on growth and some organ parameters of rats
Authors: GENC B. , SALMAN M. , TÜTÜNCÜ Ş. , ERMIŞ M. , MURUZ H.
Published: April 2020

This study aims to determine the effects of open and closed formulated standard diets supplied from different sources on growth performance and internal organ development of laboratory rats. Five-week-old 32 Wistar rats were used. A special control group diet was produced in accordance with the criteria determined by the National Research Council (NRC) (1995). Three different most preferred commercial open and closed-formula diets produced by international and local companies were used as trial groups’ diets. The experiment was carried out for 12 weeks. Weekly feed consumption, body weight change, internal organ weight, intestinal organ weigths and lengths, intestinal villi heigth and crypt depth were measured in groups. The body weight values of the control group and the first group fed with open-formula diet were found at the highest level (P <0.05). The control group diet had a positive effect on small intestine villi heigth and crypt depth (P <0.05). The nutrient contents and energy values of the diets of experimental groups were determined as different from the commercial firm notifications. As a result of the research, it is concluded that the diets prepared with open-formula give more reliable results in the growth performance and development of internal organs of Wistar rats.
Recent advances in understanding mitochondrial genome diversity
Authors: Zardoya Rafael
Published: April 2020

Ever since its discovery, the double-stranded DNA contained in the mitochondria of eukaryotes has fascinated researchers because of its bacterial endosymbiotic origin, crucial role in encoding subunits of the respiratory complexes, compact nature, and specific inheritance mechanisms. In the last few years, high-throughput sequencing techniques have accelerated the sequencing of mitochondrial genomes (mitogenomes) and uncovered the great diversity of organizations, gene contents, and modes of replication and transcription found in living eukaryotes. Some early divergent lineages of unicellular eukaryotes retain certain synteny and gene content resembling those observed in the genomes of alphaproteobacteria (the inferred closest living group of mitochondria), whereas others adapted to anaerobic environments have drastically reduced or even lost the mitogenome. In the three main multicellular lineages of eukaryotes, mitogenomes have pursued diverse evolutionary trajectories in which different types of molecules (circular versus linear and single versus multipartite), gene structures (with or without self-splicing introns), gene contents, gene orders, genetic codes, and transfer RNA editing mechanisms have been selected. Whereas animals have evolved a rather compact mitochondrial genome between 11 and 50 Kb in length with a highly conserved gene content in bilaterians, plants exhibit large mitochondrial genomes of 66 Kb to 11.3 Mb with large intergenic repetitions prone to recombination, and fungal mitogenomes have intermediate sizes of 12 to 236 Kb.
Widespread use of the “ascidian” mitochondrial genetic code in tunicates
Authors: Pichon Julien , Luscombe Nicholas M. , Plessy Charles
Published: April 2020

Background:Ascidians, a tunicate class, use a mitochondrial genetic code that is distinct from vertebrates and other invertebrates. Though it has been used to translate the coding sequences from other tunicate species on a case-by-case basis, it is has not been investigated whether this can be done systematically. This is an important because a) some tunicate mitochondrial sequences are currently translated with the invertebrate code by repositories such as NCBI GenBank, and b) uncertainties about the genetic code to use can complicate or introduce errors in phylogenetic studies based on translated mitochondrial protein sequences.

Methods:We collected publicly available nucleotide sequences for non-ascidian tunicates including appendicularians such as Oikopleura dioica, translated them using the ascidian mitochondrial code, and built multiple sequence alignments covering all tunicate classes.

Results:All tunicates studied here appear to translate AGR codons to glycine instead of serine (invertebrates) or as a stop codon (vertebrates), as initially described in ascidians. Among Oikopleuridae, we suggest further possible changes in the use of the ATA (Ile → Met) and TGA (Trp → Arg) codons.

Conclusions:We recommend using the ascidian mitochondrial code in automatic translation pipelines of mitochondrial sequences for all tunicates. Further investigation is required for additional species-specific differences.
Case Report: Colorectal cancer metastasis to a cervical lymph node – an unusual source of a neck lump
Authors: Wright Oliver J , Bashyam Anthony , Pitkin Lisa , Di Palma Silvana
Published: April 2020

Colorectal cancer (CRC) is the third most common cancer worldwide, and approximately 25% of patients already have metastases at the time of diagnosis. The most common metastatic sites for CRCs are the liver, lung, bone and brain and peritoneum. Cervical lymph node metastases in CRC are rare, particularly in the absence solid organ involvement. Here we present a case of a 73-year-old female patient who, following resection of a poorly differentiated caecal adenocarcinoma, re-presented four years later with a left level IV lymph node which was ultimately found to contain metastatic adenocarcinoma.