Antineoplastic treatment class modulates COVID-19 mRNA-BNT162b2 vaccine immunogenicity in cancer patients: a secondary analysis of the prospective Vax-On study.

BACKGROUND: Preliminary analysis from the Vax-On study did not find a correlation between cancer treatment type and antibody response to COVID-19 vaccination. We carried out a secondary subgroup analysis to verify the effects of comprehensive cancer treatment classification on vaccine immunogenicity. METHODS: The Vax-On study prospectively enrolled patients who started a two-dose messenger RNA-BNT162b2 vaccine schedule from 9 March 2021 to 12 April 2021 (timepoint-1). Those on active treatment within the previous 28 days accounted for the exposed cases. Patients who had discontinued such treatment by at least 28 days or received intravesical therapy represented the control cases. Quantification of immunoglobulin G (IgG) antibodies against the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein was carried out before the second dose (timepoint-2) and 8 weeks thereafter (timepoint-3). Seroconversion response was defined at ≥50 arbitrary units/ml IgG titer. Classification of antineoplastic agents was based on their pharmacodynamic properties. RESULTS: Three hundred and sixty-six patients were enrolled (86 and 260 as control and exposed cases, respectively). Univariate analysis revealed a significantly lower IgG titer after both doses of vaccine in subgroups treated with tyrosine kinase inhibitors (TKIs), multiple cytotoxic agents, alkylating agents, and topoisomerase inhibitors. At timepoint-3, seroconversion response was significantly impaired in the topoisomerase inhibitors and mechanistic target of rapamycin (mTOR) inhibitors subgroups. After multivariate testing, treatment with alkylating agents and TKIs was significantly associated with a reduced change in IgG titer at timepoint-2. Treatment with mTOR inhibitors resulted in a similar interaction at each timepoint. Cyclin-dependent kinase 4/6 inhibitor treatment was independently correlated with an incremental variation in IgG titer at timepoint-3. Specific subgroups (TKIs, antimetabolites, alkylating agents, and multiple-agent chemotherapy) predicted lack of seroconversion at timepoint-2, but their effect was not retained at timepoint-3. Eastern Cooperative Oncology Group performance status 2, immunosuppressive corticosteroid dosing, and granulocyte colony-stimulating factor use were independently linked to lower IgG titer after either dose of vaccine. CONCLUSIONS: Drugs interfering with DNA synthesis, multiple-agent cytotoxic chemotherapy, TKIs, mTOR and cyclin-dependent kinase 4/6 inhibitors differentially modulate humoral response to messenger RNA-BNT162b2 vaccine.

Intravesical electrostimulation versus sacral neuromodulation for incomplete spinal cord patients suffering from neurogenic non-obstructive urinary retention.

OBJECTIVES: To compare the efficacy of intravesical electrostimulation (IVES) versus sacral neuromodulation (SNM) in patients with incomplete spinal cord lesions (SCL) and neurogenic non-obstructive urinary retention (N-NOR). METHODS: In this retrospective study, 77 N-NOR patients underwent IVES (minimum 28 sessions), then after returning to voiding baseline symptoms, percutaneous first stage of SNM (lasting for minimum 4 weeks). After the two neuromodulation treatments, responders were categorized as patients experiencing both a 50% reduction of volume per catheterization per ml and a 50% reduction in number of catheterizations per day when comparing the 7-day voiding diaries at the end of both procedures to baselines. New urodynamics were performed subsequently. Responders to first stage of SNM underwent permanent SNM. RESULTS: Forty-eight patients responded to neither of the treatments, whereas 29 responded to both IVES and first-stage SNM. No significant statistical differences (P>0.05) were detected in the voiding diaries. Following the two procedures, the first sensation of bladder filling was either maintained or recovered by all responders, whereas the same 11 patients reached a bladder contractility index of >100. The 29 IVES responders lost their clinical benefits in a mean follow-up of 9.6 months. Only 10 out of the 29 patients became nonresponsive to permanent SNM, in a mean follow-up of 54 months. CONCLUSION: A strict correlation in terms of clinical and urodynamic patterns was demonstrated in patients with incomplete SCL and N-NOR, following IVES and first stage of SNM. However, voiding improvement through IVES was short-term when compared with the effects of permanent SNM.

Clinical efficacy of intravesical electrostimulation on incomplete spinal cord patients suffering from chronic neurogenic non-obstructive retention: a 15-year single centre retrospective study.

OBJECTIVE: To evaluate the clinical and urodynamic impact of intravesical electrostimulation (IVES) on incomplete spinal cord injury (SCI) patients suffering from chronic neurogenic non-obstructive urinary retention (N-NOR). METHODS: One-hundred and two patients underwent at least 28 consecutive daily IVES sessions because objective evidence of detrusor acontractility instead of hypocontractility was detected. Diary entries written at various stages by each patient were compared (7 days before the IVES cycle, 15-21 days into the cycle and 7 days before its end). Responders were patients with a mean 50% reduction in both the number of daily catheterizations and post-void residual urine. Responders underwent further urodynamics at the end of the IVES cycle; patients experiencing first sensation of bladder filling, and the mean volume of first sensation of bladder filling per ml, Qmax ml s(-1), among others, were evaluated. Nineteen individuals who repeated another IVES round were included in this study. RESULTS: Thirty-eight subjects (37.2%) responded to IVES and of those, 83.3% recovered the first sensation of bladder filling after the IVES round. Nineteen responders repeated IVES within 1 year, owing to loss of efficacy. They obtained similar voiding symptoms improvement and urodynamic results as after the first IVES cycle. A timespan of <2 years from SCI to IVES, and the presence of first sensation of bladder filling at baseline represented significant predictive parameters for IVES success (P<0.05) using χ(2)-test. CONCLUSIONS: IVES represents a possible therapeutic option for incomplete SCI patients with N-NOR.

Clinical concomitant benefits on pelvic floor dysfunctions after sacral neuromodulation in patients with incomplete spinal cord injury.

OBJECTIVES: To assess the concomitant clinical improvement in incomplete spinal cord injury patients (SCIPs) suffering from neurogenic bowel symptoms (NBSs), neurogenic lower urinary tract symptoms (NLUTSs) and neurogenic erectile dysfunction (NED) using sacral neuromodulation (SNM) for NBSs and NLUTSs. METHODS: Seventy-five SCIPs were selected. Before and during the follow-ups post-SNM, NLUTSs and NBSs were detected mainly through specific diaries. Erectile function was assessed using the International Index of Erectile Function composed of 5 questions (IIEF5). Quality of life (QoL) was measured with the Short Form 36 Health Survey questionnaire (SF-36). During the first stage, in which a permanent electrode was inserted percutaneously into the third sacral foramina and stimulated using an external generator, patients with NBSs or NLUTSs were required to improve their symptoms by at least 50% compared with baseline before proceeding to the second stage in which the generator was placed in the patient's buttock. NED patients needed to increase their IIEF5 score by at least 25% compared with baseline (evaluated initially 3 months after the second stage) in order to continue follow-up. RESULTS: Fourteen out of 37 subjects who manifested two functional pelvic dysfunctions at baseline maintained notable clinical improvement in two pelvic functions (median follow-up >3 years). Six had non-obstructive retention (NOR) and NED, six double incontinence, and two constipation with NOR. In the general and mental health domains of the SF-36, all patients improved their scores by at least 20% compared with baseline. CONCLUSIONS: SNM may be beneficial to selected incomplete SCIP with concomitant pelvic functional disturbances.