Background
Immune checkpoint inhibitors are poised to revolutionize the management of a growing number of malignancies. Unfortunately, the management of steroid-refractory immune mediated adverse ...events is based on a paucity of randomized data and limited to single center experiences. Our initial experience with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a wide variety of irAEs. As a result, we adopted the use of tocilizumab for the management of steroid refractory irAEs.
Methods
The character and clinical course of irAEs were abstracted from the medical record and analyzed. The dose of tocilizumab was 4 mg/kg given IV over one hour. C-reactive protein was drawn at first nivolumab infusion and at q two weeks (and with irAEs) thereafter. Clinical improvement was defined as either: documentation of resolution of symptoms or hospital discharge within seven days.
Results
Of the initial 87 patients that were treated with nivolumab, 34 required tocilizumab (39.1%). All patients were on corticosteroids. The majority (88.2%) were lung cancer patients. The index grade 3/4 irAE was pneumonitis in 35.3%, serum sickness/SIRS in 35.3%, cerebritis in 14.7% and one case each of hypophysitis, colitis, pancreatitis, hepatitis and immune mediated coagulopathy. Median time between first nivolumab and initiation of tocilizumab was 76 days (range 1–429). There was a statistically significant increase in C-reactive protein from a median of 23 mg/L (range 0.1–238.5) at baseline to 109.3 mg/L (21.5–350.4) at the time of index irAE, followed by a decrease to 19.2 mg/L (0.25–149) after tocilizumab (p < 0.00001). Clinical improvement was noted in 27/34 patients (79.4%). Some patients (52.9%) required a single dose, while 38.2% required two, 8.8% required three and 1 patient required four doses. Twenty-seven doses were given in the inpatient setting (49.1%). Median time to discharge was four days (range 1–27). Seventy-four percent of patients were discharged home. For the 53 doses of tocilizumab that were delivered when infliximab was an option, there was a cost savings of $141,048.72 (WAC) during the 18 month study period.
Conclusions
Tocilizumab may be a therapeutic option for the management of steroid refractory irAEs secondary to immune checkpoint blockade. However, randomized trials are needed to better elucidate the relative efficacy and safety of these agents.
Epstein-Barr virus (EBV) is a ubiquitous virus that establishes a latent infection within the host and in some cases can lead to the development of EBV-associated lymphomas, lymphoproliferative ...disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. We studied the clinical significance of detecting EBV DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of 2146 patients who had blood specimens sent to the Johns Hopkins Hospital clinical laboratory for viral quantitative real-time polymerase chain reaction assay over a 5-year period. Within this largely immunocompromised and hospitalized cohort, 535 patients (25%) had EBV detected in plasma or PBMCs. When EBV was detected in the absence of an EBV+ disease (n = 402), it was present only in PBMCs in 69% of cases. Immunocompromised patients were less likely to have EBV in plasma than in PBMCs in the absence of EBV+ disease. In patients with active, systemic EBV+ diseases (n = 105), EBV was detected in plasma in 99% of cases but detected in PBMCs in only 54%. Across a range of copy number cutoffs, EBV in plasma had higher specificity and sensitivity for EBV+ disease as compared with EBV in PBMCs. EBV copy number in plasma distinguished untreated, EBV+ lymphoma from EBV+ lymphoma in remission and EBV− lymphoma, and also distinguished untreated, EBV+ posttransplantation lymphoproliferative disorder (PTLD) from EBV+ PTLD in remission and EBV− PTLD. EBV copy number quantification is a useful diagnostic marker across the spectrum of EBV+ diseases, even among immunocompromised patients, with plasma specimens more indicative of EBV+ disease than PBMCs.
•Cell-free (plasma) EBV DNA performs better than cellular EBV DNA as a marker of a broad range of EBV+ diseases.•Within a largely immunocompromised and hospitalized cohort, detection of EBV DNA in plasma is uncommon in the absence of EBV+ disease.
Emerging efficacy data have led to the emergency use authorization or approval of COVID-19 vaccines in several countries worldwide. Most trials of COVID-19 vaccines excluded patients with active ...malignancies, and thus data on the safety, tolerability and efficacy of the vaccines in patients with cancer are currently limited. Given the risk posed by the COVID-19 pandemic, decisions regarding the use of vaccines against COVID-19 in patients participating in trials of investigational anticancer therapies need to be addressed promptly. Patients should not have to choose between enrolling on oncology clinical trials and receiving a COVID-19 vaccine. Clinical trial sponsors, investigators and treating physicians need operational guidance on COVID-19 vaccination for patients with cancer who are currently enrolled or might seek to enrol in clinical trials. Considering the high morbidity and mortality from COVID-19 in patients with cancer, the benefits of vaccination are likely to far outweigh the risks of vaccine-related adverse events. Herein, we provide operational COVID-19 vaccine guidance for patients participating in oncology clinical trials. In our perspective, continued quality oncological care requires that patients with cancer, including those involved in trials, be prioritized for COVID-19 vaccination, which should not affect trial eligibility.
Introduction and hypothesis
This narrative review describes the existing epidemiologic literature and identifies gaps regarding pelvic organ prolapse (POP) prevalence, incidence, natural history, and ...current and future service needs.
Materials and Methods
A PubMed search identified relevant citations published in 2000 or later. Pre-specified criteria were used to screen titles, abstracts, and manuscripts, including reference sections. Study findings were summarized to define what is known, identify gaps in current knowledge, and suggest priority areas for future research.
Results
The reported prevalence of POP varies widely (1–65%) based on whether its presence is ascertained by symptoms (1–31%), pelvic examination (10–50%), or both (20–65%). Most existing population-based surveys do not include physical examination data. White women from higher income countries are overrepresented in the existing literature. Incidence and natural history data are limited and consist mainly of cohorts that follow women after pregnancy or menopause. Given global increases in aging populations in well-resourced countries, the need for POP treatment is anticipated to increase in the coming decades. In lower and middle income countries (LMICs) where demographic trends are different, there is a dearth of information about anticipated POP service needs.
Conclusion
Future POP incidence, prevalence, and natural history studies should include non-white women from LMICs and should combine pelvic examination data with validated patient-reported outcome measures when feasible. Anticipated future service needs differ globally, with a greater demand for POP treatment services in well-resourced settings where aging populations are prevalent.
The abscopal effect could theoretically be potentiated when combined with immunomodulating drugs through increased antigen production. The optimal dosing and schedule of radiotherapy with ...immunotherapy are unknown, although they are actively investigated in laboratory and clinical models. Clinical data in patients treated for metastatic disease with both modalities may guide future studies.
This is a single-institution retrospective review of all patients treated with stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS) and immunomodulating therapy within 6 months before or after SBRT/SRS for metastatic cancer. Clinical and tumor characteristics were recorded, as well as SBRT/SRS details, immunotherapy details, and survival. Log-rank tests on Kaplan-Meier curves for overall survival (OS) that were calculated from the end of SBRT/SRS were used in univariate analysis and Cox proportional hazards regression for multivariate analysis.
A total of 125 patients were identified who met the inclusion criteria; 70 received SBRT, and 57 received SRS. Eighty-three patients were treated for non-small cell lung cancer, 7 patients for small cell lung cancer, and 35 patients for other cancers, with the most common one being melanoma. Fifty-three percent of patients received nivolumab, 29% pembrolizumab, 13% atezolizumab, 5% other. Twenty percent received immunotherapy before SBRT/SRS, 39% during SBRT/SRS, 41% after. Eighty-six patients had died by the time of the analysis; the median OS for the whole cohort was 9.7 months. Patients who had completed immunotherapy prior to SBRT/SRS had worse OS than those who received concurrent therapy or immunotherapy after SBRT/SRS, with a difference in median OS of 3.6 months vs. 13.0 months (p = 0.010) that was retained on multivariate analysis (p = 0.011). There was no significant difference in OS between patients receiving SRS vs. SBRT (p = 0.20), sex (p = 0.53), age >62 years (p = 0.76), or lung primary vs. others (p = 0.73) on univariate or multivariate analysis. When comparing before/concurrent to after/concurrent administration, there is a difference in survival with after/concurrent survival of 8.181 months and before survival of 13.010 months, but this was not significant (p = 0.25).
OS appears to be worse in patients who complete immunotherapy prior to SBRT/SRS compared to those receiving it concurrently or after. The design of this retrospective review may be prone to lead time bias, although the difference in median survival is longer than the 6-month window before SBRT/SRS and could only account for part of this difference. Further analysis into causes of death and toxicity and prospective studies are needed to confirm the results of this analysis.
Calcium is the key macromineral having a role in skeletal structure and function, muscle contraction, and neurotransmission. Bone remodeling is maintained through a constant balance between calcium ...resorption and deposition. Calcium deficiency is resolved through calcium supplementation, and among the supplements, water-soluble organic molecules attracted great pharmaceutical interest. Calcium glucoheptonate is a highly water-soluble organic calcium salt having clinical use; however, detailed investigations on its biological effects are limited. We assessed the effects of calcium glucoheptonate on cell viability and proliferation of osteoblast-like MG-63 cells. Calcium uptake and mineralization were evaluated using Alizarin red staining of osteoblast-like MG-63 cells treated with calcium glucoheptonate. Expression of osteogenic markers were monitored by western blotting, immunofluorescence, and qRT-PCR assays. Increased proliferation and calcium uptake were observed in the MG-63 cells treated with calcium glucoheptonate. The treatment also increased the expression of osteopontin and osteogenic genes such as collagen-1, secreted protein acidic and cysteine rich (SPARC), and osteocalcin. Calcium glucoheptonate treatment did not exert any cytotoxicity on colorectal and renal epithelial cells, indicating the safety of the treatment. This is the first report with evidence for its beneficial effect for pharmaceutical use in addressing calcium deficiency conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To report on anatomical and functional outcomes, patient satisfaction, and associated morbidity and mortality in patients undergoing LeFort colpocleisis.
This was a retrospective case series of ...LeFort colpocleisis performed from January 2000 to October 2011. Data obtained from a urogynecologic database included demographics, comorbidities, medications, and urinary and bowel symptoms. Prolapse was quantified using the pelvic organ prolapse quantification (POP-Q) examination. Operative characteristics were recorded. All patients underwent pelvic examination and POP-Q assessment at follow-up visits. Patients also were asked about urinary and bowel symptoms as well as overall satisfaction. All intraoperative and postoperative surgical complications were recorded.
Three hundred twenty-five patients underwent LeFort colpocleisis. Fifteen patients were excluded from the analysis because of incomplete data. The mean age was 81.3±5.3 years. Comorbidities were common, with 74.1% of the patients having at least one concomitant medical condition. The procedure was performed under spinal anesthesia in 67%. Additional procedures at the time of colpocleisis included incontinence procedures (79%) and dilation and curettage (46%). Mean follow-up was 45 (range 2-392) weeks. Anatomical success rate was 98.1% and patients were highly satisfied, with 92.9% reported being "cured" or "greatly improved." Complication and mortality rates were 15.2% and 1.3%, respectively.
Colpocleisis is an effective and low-risk procedure with high anatomical success rates and patient satisfaction. Associated morbidity and mortality related to the procedure are low. Colpocleisis remains an excellent surgical option for the elderly patient with advanced pelvic organ prolapse.
III.
Introduction and hypothesis
The objective was to determine age-related changes in measurements of urethral sphincter complex components in asymptomatic nulliparous women.
Methods
Eighty nulliparous ...women ≥18 years underwent 3D ultrasound of the anterior pelvic compartment in a cross-sectional study. Measurements of the urethral sphincter components (smooth muscle sphincter SMS and striated urinary sphincter SUS) and urethra including area, length, width, and distance of the SUS and SMS from the urethrovesical junction were obtained. The women were grouped into four age groups: < 30 years (group A), 30 to < 45 (group B), 45 to < 60 (group C), and ≥ 60 years (group D). Age-related differences in the measurements were determined. Inter-rater and intra-rater agreement were performed for 20 nulliparous women.
Results
There were 24, 18, 26, and 12 women in groups A, B, C, and D respectively. None of the urethral sphincter complex measurements was significantly associated with age (
p
> 0.05). No differences were found between the groups for any measurements using one-way ANOVA and multiple comparison pairwise comparison (
p
> 0.05) other than width of SMS (C > A), urethral length (C > A), and distance of SUS from urethrovesical junction (C > D). Inter-rater and intra-rater agreement were moderate for area, length, and width of SUS (intraclass correlation 0.6) and good (intraclass correlation above 0.8) for the remaining measurements.
Conclusion
Other than width of SMS, urethral length, and distance of SUS from urethrovesical junction, the dimensions of urethral sphincter complex components, as visualized by 3D endovaginal ultrasound, do not vary with age.
Background: Pelvic floor dysfunction a global major female reproductive health burden associated with genitourinary and psychosocial symptoms even after hysterectomy has been underreported in the ...developing world. The study aimed to determine the early incidence of pelvic floor dysfunction and its psychological impact among post-hysterectomy women.
Materials and Methods: It was a prospective cohort study for 52 weeks among 130 post-hysterectomy cases at the tertiary care center. Pelvic floor dysfunction was diagnosed with the Pelvic Floor Disability Index and quality of life with the Pelvic Floor Impact Questionnaire. The association of pelvic floor dysfunction with epidemiological characters was analyzed using SPSS version 20.
Results: The incidence of pelvic floor dysfunction was 7.8% and the impact on the quality of life was 2.7% among 130 post-hysterectomy cases. Age, body mass index, comorbidities like chronic obstructive lung disease, and previous abdominal surgery were statistically significant. A parity of three or more, caesarian sections with instrumental delivery and Transabdominal hysterectomy was statistically significant with pelvic floor dysfunction and Socio-Psychological effect within the same groups of patients. The most common symptoms were urinary symptoms accounting for 9(90%) followed by prolapse 5 (50%) and colorectal 4(40%) with a score of 20.82± 9.07, 7.48±4.5 and 6.97± 1.55, and quality of life was mostly impacted by bladder symptoms 3 (100%) with a score of 24.96±2.96.
Conclusion: Pelvic floor dysfunction is a common health burden among post-hysterectomy cases especially with older age, higher Body Mass Index, Chronic Obstructive Pulmonary Disease, parity of more than three and caesarian sections with instrumental delivery.
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