Effect of radiation exposure on survival after first solid cancer diagnosis in A-bomb survivors

BackgroundComparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer.MethodsWe analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases.ResultsFrom multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH_1Gy) for death from the first primary cancer was not significantly different from zero – p = 0.23, EH_1Gy = 0.038 (95 % CI: −0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH_1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH_1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001.ConclusionThere is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors.ImpactA direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.     

Mechanism Based Inhibition of Hydroxysteroid Dehydrogenases

Abstract

Steroid hormone action can be regulated not only at the receptor level but also by the enzymes that are responsible for the synthesis and degradation of biologically active steroids. Traditionally the pharmacological intervention of steroid hormone action has focused on the development of steroidal and nonsteroidal hormone receptor agonists and antagonists with appropriate pharmacokinetics. Recently, the development of selective inhibitors/inactivators of steroid metabolizing enzymes has gained momentum. This review will concentrate on the development of mechanism-based inhibitors for one class of steroid hormone transforming enzymes, the hydroxysteroid dehydrogenases.     

Changes in Steroid Concentrations with the Timing of Corticotropin Stimulation Testing in Participants with Adrenal Sufficiency

ObjectiveTo determine whether the time of day at which corticotropin stimulation testing is performed influences the steroid concentrations observed in persons with normal adrenal function.MethodsIn this retrospective, secondary analysis, participants with normal adrenal function were studied to determine whether the time of corticotropin stimulation testing influenced results. Participants consisted of 2 groups: healthy volunteers who were not suspected of having adrenal insufficiency and patients being tested for adrenal insufficiency as part of their standard of care who were subsequently shown to have normal adrenal function on the basis of a peak cortisol value of at least 20 μg/dL. A high-dose corticotropin stimulation test was performed in all participants. Baseline, peak, and delta steroid concentrations were documented after corticotropin injection. Steroid concentrations were measured by tandem mass spectrometry. Multivariate analyses adjusted for patient age, sex, and baseline steroid concentrations.ResultsWith progression through the day for the time of testing, the baseline cortisol concentration decreased, while the peak and delta cortisol concentration increased (P values: < .001, .007, .007, respectively). For 11-deoxycortisol, the baseline decreased, while peak and delta values increased with later testing (P values: .017, .012, .02, respectively). Peak aldosterone concentrations increased according to their baseline values (P < .001), but were unaffected by time. Peak and delta dehydroepiandrosterone concentrations increased with time (P = .015 and .021, respectively). Referring to the various criteria for adequate steroid responses to corticotropin available in the literature, the time-related differences in this small group of patients were insufficient to draw different conclusions about results of testing.ConclusionsCortisol, 11-deoxycortisol, and dehydroepiandrosterone values were most influenced by testing times. In patients with borderline adrenal function who are tested at different times of the day, the modest differences we observed may be sufficient to affect conclusions about whether adrenal insufficiency is present. (Endocr Pract. 2012;18:66-75)     

Comparison of clinical findings and electromyography results in patients with preliminary diagnosis of carpal tunnel syndrome

ObjectiveTo evaluate the link between EMG findings and clinical status, the Boston questionnaire and the severity of pain in patients with pre-diagnosis of carpal tunnel syndrome.MethodsA total of 85 patients (133 hands) who presented to the Physical Therapy and Rehabilitation outpatient clinic consecutively with complaints of numbness, tingling, pain and weakness in their hands were evaluated for their demographic and clinical features. After the initial evaluation, the diagnosis of CTS was confirmed by EMG. Visual analog scale (VAS), the Boston Questionnaire (Symptom Severity Scale = SSS, Functional Status Scale = FSS) and nerve conduction study results (sensory conduction velocity = SCV, distal motor latency = DML, compound muscle action potential = CMAP) were enrolled.ResultsEighty-five patients (58 female and 27 male) participated in this study yielding 133 hands (73 right hands, 60 right hands) with CTS. The mean age was 48.3 ± 10.41 years. Of all patients, 68.2 % were female and 31.8 % were male. A statistically significant relationship was found between SSS and duration of symptoms, VAS, both right and left SCV, DML and CMAP. A statistically significant relationship was found between FSS and duration of symptoms, VAS and only right SCV, DML and CMAP.ConclusionThe diagnosis of CTS should be evaluated not only as an electrodiagnostic finding, but also the clinical picture of the patients. According to our results, both SSS and FSS had good correlations with VAS and the findings of EMG. Therefore, the Boston Questionnaire can provide a standardized measure of symptom severity and functional status in patients with CTS.     

Estradiol,progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles

Background  

The production of sex steroids by follicular cells is proposed to be influenced by the maturity of the incumbent oocyte. Thus steroid levels may reflect suitability of an oocyte for IVF. We examined follicular fluids and granulosa cell production of steroid from IVF patients in order to test the relationship between steroid levels and fertilization.     

Clinical outcomes of therapeutic leukapheresis in acute promyelocytic leukemia: A single-center retrospective cohort study

BackgroundIn acute promyelocytic leukemia (APL), increased cell burden in the peripheral blood due to either the disease itself or early treatment with all-trans retinoic acid could cause hyperleukocytosis (HL) before induction chemotherapy. However, therapeutic leukapheresis has seldom been used because of concerns of subsequent coagulopathy after this invasive procedure. The aim of this study was to evaluate the effects of leukapheresis in APL, especially for efficacy and safety.MethodsWe retrospectively analyzed newly diagnosed patients with APL from January 2009 to March 2022. Among 323 patients, 85 had white blood cell count above 40 × 10⁹/L before induction chemotherapy. Thirty-nine patients were initially treated with leukapheresis, whereas the other 46 were not. Clinical and laboratory parameters between these groups were compared.ResultsThere was a trend toward favorable 30-day survival rate for the leukapheresis group compared with the non-leukapheresis group (76.9% and 67.4%; P = 0.24). The complications including subsequent intensive unit care (P = 0.23), severe hemorrhagic events (P = 0.13) showed no significant differences between the two groups. The patients were divided into subcohorts, and the survival rates of the leukapheresis and non-leukapheresis groups were 92.3% (95% confidence interval [CI], 77.8%–100.0%) versus 58.3% (95% CI, 38.6%–78.1%) (P = 0.03) in “sequential HL” and 76.7% (95% CI, 61.5%–91.8%) versus 54.8% (95% CI, 37.3%–72.4%) (P = 0.03) in “symptomatic HL,” respectively. Moreover, in the “sequential HL” subcohort, the cumulative incidence of differentiation syndrome and following adverse events were significantly lower in the leukapheresis group.ConclusionsIn APL with “sequential HL” or “symptomatic HL” from either the disease itself or the effect of all-trans retinoic acid, therapeutic leukapheresis could be applied to reduce leukemic cell burden without significant risks.     

Protective role of IL-18 −137G/C polymorphism in a North Indian population with asthma: A pilot study

BackgroundIL-18, a pleiotropic, pro-inflammatory cytokine that plays a major role in innate as well as acquired immunity, has been implicated in asthma etiology and this is the first study investigating the role of IL-18 ?137G/C (rs 187238) promoter polymorphism in asthma pathogenesis in a North Indian population.MethodsA pilot study was conducted with a total of 824 subjects, out of which 410 were asthma patients including 323 patients suffering from allergic rhinitis and 414 healthy controls from regions of North India. Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR) was used for genotyping the IL-18 ?137G/C polymorphism.ResultsWhile the homozygous wild (GG) genotype was equally prevalent in asthma patients as well as control subjects (70.0%), the homozygous mutant (CC) genotype was more prevalent among the controls (8.0%) than in asthma patients (3.4%), which yielded a significant protection or decreased risk towards asthma. Statistical analysis revealed Odds Ratio (OR) = 0.43 (95% CI = 0.21–0.85), Chi² (χ²) = 6.93 and p-value = 0.008 (p < 0.005). Moreover, a few asthma phenotypic traits also revealed significant protective associations with the polymorphism.ConclusionsThe IL-18 ?137G/C polymorphism confers a significant protection from asthma in the studied North Indian population. This is the first study to report the protective association of the polymorphism with the disease.     

Diagnosis and treatment of lung cancer in Denmark during the COVID-19 pandemic

BackgroundWe examined the number of lung cancers diagnosed, the quality of care and the socio-economic and clinical characteristics among patients with lung cancer during the COVID-19 pandemic compared to previous years.MethodsWe included all patients ≥ 18 years old diagnosed with lung cancer from 01 January 2018 to 31 August 2021 as registered in the Danish Lung Cancer Registry. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of the associations between the pandemic and socioeconomic and clinical factors, and indicators of quality.ResultsWe included 18,113 patients with lung cancer (82.0% non-small cell lung cancer (NSCLC)), which was similar to the preceding years, although a decline in NSCLC cases occurred during the first lockdown period in 2020. No difference in distribution of income or educational level was observed. No difference was observed in the quality of treatment – as measured by curative intent, proportion of patients resected or who died within 90 days of diagnosis.ConclusionUsing nationwide population-based data, our study reassuringly shows no adverse effects of the COVID-19 pandemic on the diagnosis, socio-economic characteristics nor quality of treatment of lung cancer, as compared to the preceding years.     

Seasonal variations of date of diagnosis and birth for neuroblastoma patients in Italy

BackgroundAnalysis of seasonal variation of diagnosis or birth of childhood cancers may provide useful insight about possible aetiological risk factors, such as infectious agents and environmental exposures, but studies on neuroblastoma are lacking.ProcedureTwo thousand seven hundred fifty-six cases of neuroblastoma, diagnosed between 1980 and 2010, registered in the Italian Neuroblastoma Registry, were included in the study. Subgroup analyses were carried out by age, gender and stage at diagnosis. Seasonal trend was assessed by a harmonic function in a Poisson regression model, adjusted for the number of live births.ResultsNo trend in the date of diagnosis was found either in the entire cohort or in the various sub-groups. Similarly, a seasonal trend of birth was not observed in the whole cohort. Conversely, in the subgroup of infants with stage 4S, a significant peak of July births was found (23.6% increment from the average, p = 0.042). The summer peak was confirmed after stratifying 4S patients by gender and period of diagnosis.ConclusionsA major effect of risk factors related to seasonality does not appear to affect the risk of developing neuroblastoma. However, the time pattern of birth observed by stage at diagnosis is consistent with the hypothesis that Stage 4S is a distinct disease with probably a different aetiology, as indicated by investigations on its metastatic pattern and its peculiar gene expression. An aetiological role of seasonally related factors, e.g., favouring the survival of defective neural crest stem cells, remains speculative and need confirmation by independent studies.     

Transvenous lead extraction on uninterrupted anticoagulation: A safe approach?

IntroductionCurrent guidelines advocate reviewing peri-procedural anticoagulation on individual case basis for transvenous lead extraction (TLE). We investigated the safety of TLE on uninterrupted warfarin with therapeutic INR.MethodsRetrospective registry of consecutive patients undergoing TLE on uninterrupted warfarin (Warfarin Group) across two centres. Age and sex matched controls not on anticoagulation (No-Warfarin Group) and undergoing TLE over the same time-period were included. Both groups were compared over one-year.Results121 TLEs over 18-months. 22 patients on uninterrupted anticoagulation were compared to 22 controls. Groups were well matched for baseline demographics other than INR. Warfarin group had mean INR of 2.2 ± 0.6 (range 2–3.5). Primary end point was procedural safety and efficacy. Amongst cases, 43/45 (96%) leads were removed in their entirety compared to 37/40 (93%) in controls (p = 0.66). In the cases, these included 44% defibrillator, 47% pace-sense and 9% CS leads of average duration 7yrs. There was no reported tamponade, haemothorax or procedural mortality in either group. One patient amongst cases required inotropic support while two patients amongst controls had device-site haematomas. No significant difference reported in Hb drop post-procedure or overall complication rate between the groups (p = 0.11,0.32). Cox regression showed a significant association between procedural success and device infection, number of leads extracted, serum creatinine (p = 0.03, 0.04, 0.02). Over a 1-year follow-up, there was lead displacement in one case and one control had infection of the re-implanted device.ConclusionTLE can be carried out safely in anticoagulated patients with therapeutic INRs. Larger multicentre studies are required to confirm these findings.     

The Evaluation of Low- and High-Dose Steroid Treatments in Subacute Thyroiditis: A Retrospective Observational Study

ObjectiveThe optimal steroid regimen in the treatment of subacute thyroiditis (SAT) is controversial. This study aims to compare low- and high-dose steroid regimens in the treatment of SAT.MethodsA single-center, retrospective observational cohort study with up to 1 year of follow-up was conducted. A total of 44 patients in the 16-mg methylprednisolone (MPS) group and 47 patients in the 48-mg MPS group were enrolled. Clinical and laboratory findings from the time of diagnosis to 1-year of the follow-up were assessed. Treatment response, recurrence, and hypothyroidism (HPT) rates were evaluated.ResultsClinical symptoms, sedimentation rates, C-reactive protein, and thyroid hormone levels of the patients were similar in the 2 groups. Recovery was achieved in all patients at the end of the treatments; however, treatment duration needed to be extended for 6 (13.6%) and 1 (2.1%) of the patients in the 16-mg and 48-mg MPS groups, respectively. The 48-mg MPS group had a higher SAT recurrence rate than the 16-mg MPS group (P = .04). Logistic regression analysis suggested that a lower thyroid-stimulating hormone level at the end of the treatment was a predictor of recurrence (β = –0.544, P = .014, 95% CI: 0.376-0.895). While the transient HPT rate was 10 (21.3%) and 10 (22.7%) in the 48-mg and 16-mg MPS groups, respectively, a permanent HPT developed in 5 (10.6%) of patients in the 48-mg MPS and 3 (6.8%) in the 16-mg MPS group. The permanent and transient HPT rates were determined to be similar in the low- and high-dose groups (P > .05).ConclusionLow-dose steroid therapy may be sufficient to achieve a complete recovery and better outcomes in SAT.