Comparison of outcomes between medical and surgical treatment in dogs with prostatic adenocarcinoma: a retrospective study

Background Prostatic cancer is uncommon in dogs. Dogs with prostatic carcinoma have been reported to have a poor prognosis. Information regarding prognosis with various surgery options as well as prognosis with surgical vs. medical treatment is lacking. This retrospective study compares the outcomes of medical management to surgical treatment in dogs with prostatic adenocarcinoma and assesses the surgical outcomes of patients who underwent total prostatectomy (TP) and prostatocystectomy (TPC). The medical records of 41 dogs with prostatic adenocarcinoma, between February 2008 and June 2019, were reviewed for information on signalment, clinical signs in the initial evaluation, preoperative diagnostic imaging findings, treatment type (non-surgical or surgical), surgery type, postoperative complications, adjunctive medical therapy, and survival time. The dogs were divided into non-surgical (n = 12) or surgical (n = 29) groups. The surgical group was subdivided into the TP (n = 20) and TPC (n = 9) subgroups. Results Age was not significantly different between the surgical (median 13.1 years [8.4–15.4] years) and the non-surgical groups (median 10.8 [7.7–15.3] years). Body weight (BW) was also not significantly different between the surgical (median 6.8 kg [2.4–34.5 kg]) and non-surgical groups (median 6.4 kg [3.7–9.12 kg]). The overall median survival time (MST) from the initial evaluation was significantly longer in the surgical than in the non-surgical group (337 vs. 90.5 days). The postoperative MST was significantly longer in the TP group than in the TPC subgroup (510 vs. 83 days). As TPC was performed in cases of tumor progression, its postoperative complications were severe, resulting in a shorter MST. Ten (50%) and 6 patients (30%) in the TP subgroup postoperatively showed mild and severe urinary incontinence, respectively, whereas all patients in TPC subgroup did show severe incontinence. Conclusion Results of the study suggest that surgical treatment of prostatic carcinoma results in longer survival times over medical management alone. In particular, TP might be recommended for improving survival time and quality of life in canine prostatic adenocarcinoma that does not infiltrate the bladder. Early detection is key for a survival advantage with surgical treatment.

Racial, Ethnic, and Sex Disparities in Nail Psoriasis Clinical Trials: A Systematic Review

<b><i>Introduction:</i></b> Nail psoriasis (NP) disproportionally affects quality of life in females versus males. Demographics of NP research cohorts are not well characterized. In this systematic review, we characterize the representation of racial/ethnic groups and women in NP randomized clinical trials (RCTs). <b><i>Methods:</i></b> A systematic search of MEDLINE was performed; RCTs of NP pharmacologic treatments or cutaneous psoriasis/psoriatic arthritis with the number of NP patients described were included. <b><i>Results:</i></b> Overall, 45 RCTs were analyzed, with 91.1% reporting sex, and 67.9% of participants were men. 7/41 (17%) studies reporting sex included ≥45% female participants. Of 45 RCTs, 35.6% reported race and/or ethnicity. Of the 22 studies with ≥1 US-based site, 13 (59%) reported race/ethnicity; 3 out of 23 (13%) studies with &#x3c;1 US-based site reported these data. Enrollment of nonwhite participants was significantly lower than representation within the US census (13.4% vs. 39.9%; <i>p</i> &#x3c; 0.001). Treatment type, route of administration, location with ≥1 US-based site, funding, and journal type were significantly associated with race/ethnicity reporting (<i>p</i> &#x3c; 0.05 all comparisons). <b><i>Discussion/Conclusion:</i></b> Reporting of racial/ethnic demographics is lacking in NP RCTs. Women and racial/ethnic minorities remain underrepresented in NP research. There is a need for increased reporting and diversification of NP clinical trial participants.

Twenty Years On: RECIST as a Biomarker of Response in Solid Tumours an EORTC Imaging Group – ESOI Joint Paper

Response evaluation criteria in solid tumours (RECIST) v1.1 are currently the reference standard for evaluating efficacy of therapies in patients with solid tumours who are included in clinical trials, and they are widely used and accepted by regulatory agencies. This expert statement discusses the principles underlying RECIST, as well as their reproducibility and limitations. While the RECIST framework may not be perfect, the scientific bases for the anticancer drugs that have been approved using a RECIST-based surrogate endpoint remain valid. Importantly, changes in measurement have to meet thresholds defined by RECIST for response classification within thus partly circumventing the problems of measurement variability. The RECIST framework also applies to clinical patients in individual settings even though the relationship between tumour size changes and outcome from cohort studies is not necessarily translatable to individual cases. As reproducibility of RECIST measurements is impacted by reader experience, choice of target lesions and detection/interpretation of new lesions, it can result in patients changing response categories when measurements are near threshold values or if new lesions are missed or incorrectly interpreted. There are several situations where RECIST will fail to evaluate treatment-induced changes correctly; knowledge and understanding of these is crucial for correct interpretation. Also, some patterns of response/progression cannot be correctly documented by RECIST, particularly in relation to organ-site (e.g. bone without associated soft-tissue lesion) and treatment type (e.g. focal therapies). These require specialist reader experience and communication with oncologists to determine the actual impact of the therapy and best evaluation strategy. In such situations, alternative imaging markers for tumour response may be used but the sources of variability of individual imaging techniques need to be known and accounted for. Communication between imaging experts and oncologists regarding the level of confidence in a biomarker is essential for the correct interpretation of a biomarker and its application to clinical decision-making. Though measurement automation is desirable and potentially reduces the variability of results, associated technical difficulties must be overcome, and human adjudications may be required.

Retrospective validation of the postnatal Growth and Retinopathy of Prematurity (G-ROP) criteria in a Swiss cohort

Background Currently used screening criteria for retinopathy of prematurity (ROP) show high sensitivity for predicting treatment-requiring ROP but low specificity; over 90% of examined infants do not develop ROP that requires treatment (type 1 ROP). A novel weight gain-based prediction model was developed by the G-ROP study group to increase the specificity of the screening criteria and keep the number of ophthalmic examinations as low as possible. This retrospective cohort study aimed to externally validate the G-ROP screening criteria in a Swiss cohort. Methods Data from 645 preterm infants in ROP screening at Inselspital Bern between January 2015 and December 2019 were retrospectively retrieved from the screening log and analysed. The G-ROP screening criteria, consisting of 6 trigger parameters, were applied in infants with complete data. To determine the performance of the G-ROP prediction model for treatment-requiring ROP, sensitivity and specificity were calculated. Results Complete data were available for 322 infants who were included in the analysis. None of the excluded infants had developed type 1 ROP. By applying the 6 criteria in the G-ROP model, 214 infants were flagged to undergo screening: among these, 14 developed type 1 ROP, 9 developed type 2 ROP, and 43 developed milder stages of ROP. The sensitivity for predicting treatment-requiring ROP was 100% (CI, 0.79–1.00), and the specificity was 41% (CI, 0.35 –0.47). Implementing the novel G-ROP screening criteria would reduce the number of infants entering ROP screening by approximately one third. Conclusions The overall prevalence of treatment-requiring ROP was low (2.15%). Previously published performance parameters for the G-ROP algorithm were reproducible in this Swiss cohort. Importantly, all treatment-requiring infants were correctly identified. By using these novel criteria, the burden of screening examinations could be significantly reduced.

Development of an automated system for adaptive post-weld treatment and quality inspection of linear welds

High-frequency mechanical impact (HFMI) treatment is a well-documented post-weld treatment to improve the fatigue life of welds. Treatment of the weld toe must be performed by a skilled operator due to the curved and inconsistent nature of the weld toe to ensure an acceptable quality. However, the process is characterised by noise and vibrations; hence, manual treatment should be avoided for extended periods of time. This work proposes an automated system for applying robotised 3D scanning to perform post-weld treatment and quality inspection of linear welds. A 3D scan of the weld is applied to locally determine the gradient and curvature across the weld surface to locate the weld toe. Based on the weld toe position, an adaptive robotic treatment trajectory is generated that accurately follows the curvature of the weld toe and adapts tool orientation to the weld profile. The 3D scan is reiterated after the treatment, and the surface gradient and curvature are further applied to extract the quantitative measures of the treatment, such as weld toe radius, indentation depth, and groove deviation and width. The adaptive robotic treatment is compared experimentally to manual and linear robotic treatment. This is done by treating 600-mm weld toe of each treatment type and evaluating the quantitative measures using the developed system. The results showed that the developed system reduced the overall treatment variance by respectively 26.6% and 31.9%. Additionally, a mean weld toe deviation of 0.09 mm was achieved; thus, improving process stability yet minimising human involvement.

The Impact of COVID-19 on the Delivery of Systemic Anti-Cancer Treatment at Guy’s Cancer Centre

Background: This study aimed to assess the outcome of cancer patients undergoing systemic anti-cancer treatment (SACT) at our centre to help inform future clinical decision-making around SACT during the COVID-19 pandemic. Methods: Patients receiving at least one episode of SACT for solid tumours at Guy’s Cancer Centre between 1 March and 31 May 2020 and the same period in 2019 were included in the study. Data were collected on demographics, tumour type/stage, treatment type (chemotherapy, immunotherapy, biological-targeted) and SARS-CoV2 infection. Results: A total of 2120 patients received SACT in 2020, compared to 2449 in 2019 (13% decrease). From 2019 to 2020, there was an increase in stage IV disease (62% vs. 72%), decrease in chemotherapy (42% vs. 34%), increase in immunotherapy (6% vs. 10%), but similar rates of biologically targeted treatments (37% vs. 38%). There was a significant increase in 1st and 2nd line treatments in 2020 (68% vs. 81%; p < 0.0001) and reduction in 3rd and subsequent lines (26% vs. 15%; p = 0.004) compared to 2019. Of the 2020 cohort, 2% patients developed SARS-CoV2 infections. Conclusions: These real-world data from a tertiary Cancer Centre suggest that despite the challenges faced due to the COVID-19 pandemic, SACT was able to be continued without any significant effects on the mortality of solid-tumour patients. There was a low rate (2%) of SARS-CoV-2 infection which is comparable to the 1.4%-point prevalence in our total cancer population.

Date of Admission during COVID-19 Pandemic Impacted Patient Outcomes in Addition to the Higher Efficacy of Tocilizumab Plus High-Dose Corticosteroid Therapy Compared to Tocilizumab Alone

Background: The evidence for the efficacy of glucocorticoids combined with tocilizumab (TCZ) in COVID-19 comes from observational studies or subgroup analysis. Our aim was to compare outcomes between hospitalized COVID-19 patients who received high-dose corticosteroid pulse therapy and TCZ and those who received TCZ. Methods: A retrospective single-center study was performed on consecutive hospitalized patients with severe COVID-19 between 1 March and 23 April 2020. Patients treated with either TCZ (400–600 mg, one to two doses) and methylprednisolone pulses (MPD-TCZ group) or TCZ alone were analyzed for the occurrence of a combined endpoint of death and need for invasive mechanical ventilation during admission. The independence of both treatment groups was tested using machine learning classifiers, and relevant variables that were potentially different between the groups were measured through a mean decrease accuracy algorithm. Results: An earlier date of admission was significantly associated with worse outcomes regardless of treatment type. Twenty patients died (27.0%) in the TCZ group, and 33 (44.6%) died or required intubation (n = 74), whereas in the MPD-TCZ group, 15 (11.0%) patients died and 29 (21.3%) patients reached the combined endpoint (n = 136; p = 0.006 and p < 0.001, respectively). Machine learning methodology using a random forest classifier confirmed significant differences between the treatment groups. Conclusions: MPD and TCZ improved outcomes (death and invasive mechanical ventilation) among hospitalized COVID-19 patients, but confounding variables such as the date of admission during the COVID-19 pandemic should be considered in observational studies.

Treatment-Specific Hippocampal Subfield Volume Changes With Antidepressant Medication or Cognitive-Behavior Therapy in Treatment-Naive Depression

Background: Hippocampal atrophy has been consistently reported in major depressive disorder with more recent focus on subfields. However, literature on hippocampal volume changes after antidepressant treatment has been limited. The first-line treatments for depression include antidepressant medication (ADM) or cognitive-behavior therapy (CBT). To understand the differential effects of CBT and ADM on the hippocampus, we investigated the volume alterations of hippocampal subfields with treatment, outcome, and chronicity in treatment-naïve depression patients.Methods: Treatment-naïve depressed patients from the PReDICT study were included in this analysis. A total of 172 patients who completed 12 weeks of randomized treatment with CBT (n = 45) or ADM (n = 127) were included for hippocampal subfield volume analysis. Forty healthy controls were also included for the baseline comparison. Freesurfer 6.0 was used to segment 26 hippocampal substructures and bilateral whole hippocampus from baseline and week 12 structural MRI scans. A generalized linear model with covariates of age and gender was used for group statistical tests. A linear mixed model for the repeated measures with covariates of age and gender was used to examine volumetric changes over time and the contributing effects of treatment type, outcome, and illness chronicity.Results: Of the 172 patients, 85 achieved remission (63/127 ADM, 22/45 CBT). MDD patients showed smaller baseline volumes than healthy controls in CA1, CA3, CA4, parasubiculum, GC-ML-DG, Hippocampal Amygdala Transition Area (HATA), and fimbria. Over 12 weeks of treatment, further declines in the volumes of CA1, fimbria, subiculum, and HATA were observed regardless of treatment type or outcome. CBT remitters, but not ADM remitters, showed volume reduction in the right hippocampal tail. Unlike ADM remitters, ADM non-responders had a decline in volume in the bilateral hippocampal tails. Baseline volume of left presubiculum (regardless of treatment type) and right fimbria and HATA in CBT patients were correlated with a continuous measure of clinical improvement. Chronicity of depression had no effect on any measures of hippocampal subfield volumes.Conclusion: Two first-line antidepressant treatments, CBT and ADM, have different effects on hippocampal tail after 12 weeks. This finding suggests that remission achieved via ADM may protect against progressive hippocampal atrophy by altering neuronal plasticity or supporting neurogenesis. Studies with multimodal neuroimaging, including functional and structural analysis, are needed to assess further the impact of two different antidepressant treatments on hippocampal subfields.

Delay in Diagnosis of Cervical Cancer in Afghanistan: A Pilot Cross-Sectional Survey

Objectives: The present study aimed to investigate the potential delays in healthcare seeking and diagnosis of women with cervical cancer (CC) in Afghanistan.Methods: Clinical records of three hospitals in Kabul were searched for CC cases, and the women identified were interviewed by a trained physician using a semi-structured questionnaire. The main outcomes were the prevalence of potential delays over 90 days (1) from symptoms onset to healthcare seeking (patient delay), and (2) from first healthcare visit to CC diagnosis (healthcare delay). Information was also collected on: type and stage of CC, diagnostic test utilized, familiarity for CC, signs and symptoms, treatment type, and potential reasons for delaying healthcare seeking.Results: 31 women with CC were identified, however only 11 continued their treatment in the study hospitals or were reachable by telephone, and accepted the interview. The mean age was 51 ± 14 years, and only 18.2% had a previous history of seeking medical care. Patient delay was seen in 90.9% of the women (95% CI: 58.7–99.8), with a median of 304 ± 183 days. Instead, healthcare delay was found in 45.4% (95% CI: 16.7–76.6), with a median of 61 ± 152 days. The main reasons for patient delays were unawareness of the seriousness of the symptoms (70.0%) and unwillingness to consult a healthcare professional (30.0%). None of the women ever underwent cervical screening or heard of the HPV vaccination.Conclusions: Given the global effort to provide quality health care to all CC patients, Afghanistan needs interventions to reduce the delays in the diagnosis of this cancer, for instance by improving all women's awareness of gynecological signs and symptoms.

Integrated Rehabilitation for Children with Cerebral palsy: A Prospective Observational Study

Objectives: This study aimed to analyse: 1) the clinical effectiveness and safety of traditional Korean Medicine (TKM) and frequency of TKM therapies used and their relationship with conventional treatments.Methods: This prospective observational study enrolled children with cerebral palsy (CP) aged 6-78 months (n=126). The children who used herbal medication for >30 days or acupuncture treatment >12 sessions within 6 months were defined as the integrated rehabilitation (IR) group; the remaining participants were included in the conventional rehabilitation (CR) group.Results: Changes in the Gross Motor Function Measure-66 (GMFM-66) were greater in the IR group (6.4±6.1) than in the CR group (4.6±5.8). The reduction in the number of other health problems was greater in the IR group than in the CR group. The GMFM-66 improvement was greatest in gross motor function classification system level 1. There was no between-group difference in the frequency of rehabilitation therapy (10.9±6.6 and 12.0±9.9 in the IR and CR groups, respectively).Conclusion: TKM may offer additional benefits in terms of the GMFM-66 score and other health problems. However, there is a need for further randomized controlled trials involving a restricted CP type and a controlled treatment type and intensity to confirm these findings.