Immunotherapy: RAPID ACCESS TO VIRUS-SPECIFIC T CELLS FOR ADOPTIVE IMMUNOTHERAPY FOR COMPASSIONATE USE IN AUSTRALIA

Background & Aim: Adoptive T cell immunotherapy holds great promise for the treatment of viral complications. Our group has been developing and trialling virus-specific T cell therapies for more than 20 years. Recently, we have generated a repository of multi-virus-specific T cells for our clinical trials. Unfortunately, for many patients with viral complications, there is no suitable trial through which to access these therapies. In Australia, the Therapeutic Goods Administration has a Special Access Scheme (SAS) to enable provision of unapproved therapies for compassionate use. Our research group is now a leading Australian provider of "off-the-shelf" and custom-grown allogeneic virus-specific T cells to hospitals for patients with no other treatment options. Methods, Results & Conclusion(s): We have generated a repository of multi-virus-specific T cells from 20 healthy donors, with up to 150 doses of T cells per donor generated from a single blood sample. Each product batch is thoroughly characterised in terms of viral antigen specificity, HLA restriction and alloreactivity. These T cells target a combination of Epstein-Barr virus, cytomegalovirus, BK polyomavirus, John Cunningham virus and adenovirus epitopes. We have also generated a repository of SARS-CoV-2-specific T cells and occasionally grow custom patient-specific batches of T cells from nominated donors, on request. Since 2008, we have provided virus-specific T cells to 15 hospitals across Australia, and the volume of supply requests has significantly increased in recent years, as clinicians have gained interest in adoptive immunotherapy. In 2022, we provided T cells for 26 patients via the SAS. The majority were experiencing post-transplant complications, including cytomegalovirus disease, BK virus-associated haemorrhagic cystitis and post-transplant lymphoproliferative disorder. Through our clinical trials, we have developed rigorous processes for T cell therapy manufacture and characterisation, in addition to a computer-based selection algorithm, which we apply to SAS cases. As these cases are not part of a clinical trial, concomitant therapy varies, and monitoring is not uniform. However, we have received reports of clinical benefit from adoptive T cell therapy. These include cases of reduction in viral load, improvement in symptoms, and complete resolution of infection. We believe that these promising T cell therapies should be available to hospitals through a nationally funded centre for cellular therapies for critically ill patients.Copyright © 2023 International Society for Cell & Gene Therapy

Progression of Overactive Bladder Symptoms in Patients with Prior Sars-Cov-2 Infection

INTRODUCTION AND OBJECTIVE: Infection with SARS-CoV- 2 can result in de novo or worsening genitourinary (GU) symptoms, such as frequency, urgency, nocturia, and pain/pressure, also referred to as COVID-19 associated cystitis (CAC). The aim of this study was to follow progression of OAB symptoms in patients that previously reported new or worsening OAB symptoms after COVID-19 diagnosis. METHOD(S): 19,128 individuals from a Beaumont COVID-19 serology study, were invited to participate in a follow-up study, with 2,137 subsequent respondents. Participants were divided into a COVID-, Ser+ (positive serology test only) or PCR+ (positive PCR test) groups. Initially, patients were asked to score their OAB symptoms retrospectively prior to the pandemic (baseline) and at present time (day 0). Participants were subsequently asked to score their symptoms at 2-, 4-, 8- and 12-months follow-up. Participants that obtained COVID-19 diagnosis during follow-up phase were excluded from the study. GU symptoms were assessed using the ICIQ-OAB. The minimal important difference (MID) of ICIQ-OAB of 1 is considered a significant change. Data was collected between May 2021 and July 2022. RESULT(S): Of 2,137 participants, 564 (26.4%) previously tested positive for COVID, and 1,573 (73.6%) were COVID naive (COVID-). Of these, 592 participants reported a >=1 unit increase in OAB score at study onset (Day 0) compared to pre-pandemic;243 (41%) were COVID-, 129 (21.8%) had positive serology test (Ser+), and 220 (37.2%) were COVID+ based on PCR test (PCR+). OAB score of these three cohorts were similar at pre-pandemic (2.71 vs 2.97 vs 2.53;p=0.193) but significantly higher at start of study (day 0) in PCR+ versus COVID- or Ser+ groups (5.83 vs 5.12 vs 5.33;p=0.019). In prospective follow-up, change in ICIQ-OAB scores from baseline were recorded at 2, 4, 8 and 12 months. At day 0, both Ser+ and PCR+ cohorts had significantly higher change in OAB score than COVID- group (2.8 and 3.11 vs 2.16;p=0.001). However, after 12 months follow-up, change in OAB score was similar between COVID- (1.86), Ser+ (2.15) and PCR+ (2.09). By 12 months, 74% of COVID-, 80.5% of Ser+ and 72.4% of PCR+ participants still reported significant increase in ICIQ-OAB scores from pre-pandemic levels. CONCLUSION(S): We previously demonstrated that COVID-19 infections increases the risk for developing CAC. COVID infected individuals with CAC take up to 12 months to reach levels of COVIDpatients with baseline elevated OAB Symptoms. Elevated ICIQ-OAB scores in COVID- participants may be contributed to other consequences of the pandemic such as elevated stress and depression.

Long Term Outcomes of Covid-19 Associated Cystitis (Cac)

INTRODUCTION AND OBJECTIVE: COVID-19 associated cystitis (CAC) is a newly-described condition associated with new onset or exacerbations of baseline urinary symptoms (e.g. overactive bladder (OAB) symptoms) that may present as a manifestation of Long COVID. Little is known on the management and long-term outcomes for patients suspected of having CAC. In this study we aim to assess the long term efficacy of conservative OAB the on their symptoms. METHOD(S): In this prospective cohort study, we identified patients with CAC 10-14 weeks following discharge from 2 academic downtown Detroit hospitals with new or worsening OAB during 5/22/ 2020 to 12/31/2020. Symptoms were assessed at baseline and at 21- 28 months post-discharge using the AUA's 5 symptom OAB assessment tool and 4 quality-of-life (QoL) symptoms, based on gender and changes in urinary symptom status. RESULT(S): A total of 350 patients with CAC were identified, of which 250 (71%) had new onset, and 100 (29%) had worsening OAB symptoms after COVID hospitalization (Table 1). Follow up at 21- 28 months revealed significant decreases in median OAB and QoL scores for all groups (Table 2). Overall, 270 (87%) of the 310 patients improved with standard therapies (e.g. behavioral modification), with a decrease in the OAB and Qol score from 18 and 19 to 7 and 8 respectively. Of the 250 patients with new onset symptoms, 220 (95.4%) had improvement in symptoms, whereas, of those with existing OAB symptoms only 60 (60.7%) improved. In the later, OAB and Qol scores decreased by 6 points compared with 9-10 in the new onset group, with a lack of return to baseline status. No differences were noted among improvements in symptoms between females and males. CONCLUSION(S): We hereby report the first long-term follow-up of patients who developed CAC and assessed the prognosis of CAC in Long COVID. We found that after 21-28 months, only 13% (40/310) of patients had persistent lower urinary tract symptoms. Patients with Long COVID and CAC may be reassured that symptoms resolves in vast majority of cases and that supportive and reversible treatment should be recommended.

Impact of Crystalloid Administration on Patients Receiving Haploidentical Allogeneic Stem Cell Transplant (Haplo SCT) with Post Transplant Cytoxan Prophylaxis (PtCy): a Quality Improvement Initiative

Background: Crystalloid fluid administration has traditionally played an important role in prevention of hemorrhagic cystitis with high dose cyclophosphamide. Cryopreservation of stem cells in the era of the COVID pandemic has further led to an increase in crystalloid use. Excess fluid administration over a short duration could lead to volume overload, respiratory failure and impact overall survival. Method(s): A retrospective chart review was conducted on patients receiving PtCy following Haplo SCT at UVA Medical Center from September 2016 through August 2022. Internal BMT quality audit in June 2021 identified increased rate of ICU transfers and respiratory failure amongst patient receiving PtCy due to fluid overload. Hence our PtCy hydration was reduced, with IV fluid administration decreasing from 200 mL/ hr over 62 hours to 100 mL/hr over 12 hours. Urine output parameters placed to administer Cytoxan were also removed. We present our quality improvement project demonstrating outcomes pre and post intervention. Result(s): All demographic patient and transplant-related data was collected during the period of hospitalization for Haplo SCT [Table 1]. Pre-intervention spanned 9/2016-8/2021. Our analysis identified higher than expected rates of respiratory (Table Presented) failure prompting intervention on 8/2021. Post-intervention spanned 8/2021-8/2022. Pre-intervention, 45% of patients receiving Haplo SCT developed respiratory failure (defined as a new hypoxia) in the 30 day post-transplant period. Of these, 93% had volume overload. Mechanical ventilation was required in 21%. Complication rates included ICU transfer - 30%, AKI - 39%, and renal replacement therapy - 18%. Three percent (1 pt) developed hemorrhagic cystitis requiring bladder irrigation. Median LOS was 31.0 days. Post-intervention, average IV crystalloid received was reduced by about 15L. Median diuretic use reduced by 40%. No instances of respiratory failure, mechanical ventilation, ICU transfer, AKI or renal replacement therapy occurred in this group. Median LOS was 26.5 days. There were no cases of hemorrhagic cystitis. Please refer Figure 1. (Figure Presented) (Figure Presented) Conclusion(s): This single center quality improvement initiative shows that reducing IV crystalloid administration with PtCy is associated with a reduction in respiratory failure and other adverse clinical outcomes, without observed increase in hemorrhagic cystitis. Larger multi-center studies are needed to validate this finding.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Centering Group Treatment for Women With Interstitial Cystitis/Bladder Pain Syndrome: A Prospective, Parallel-Group Cohort Study

Importance: Women with interstitial cystitis/bladder pain syndrome (ICBPS) face isolation and treatment challenges. Group medical visits using Centering models have successfully treated other conditions but have not been explored in ICBPS. Objective(s): This study aimed to describe ICBPS pain and symptom control comparing standard treatment alone versus standard treatment augmented with Centering visits. Study Design: This prospective cohort study recruited women with ICBPS receiving standard care (control) or standard care augmented with group Centering. We administered validated questionnaires at baseline and monthly for 12 months. The primary outcome was change in the pain numerical rating scale, with Patient-Reported Outcomes Measurement Information System Pain Interference Scale and Bladder Pain/Interstitial Cystitis Symptom Score change as secondary measures. Result(s): We enrolled 45 women (20 Centering, 25 controls). Centering had significantly better numerical rating scale pain scores at 1 month (mean difference [diff], -3.45) and 2 months (mean diff, -3.58), better Patient-Reported Outcomes Measurement Information System Pain Interference Scale scores at 1 month (mean diff, -10.62) and 2 months (mean diff, -9.63), and better Bladder Pain/Interstitial Cystitis Symptom Score scores at 2 months (mean diff, -13.19), and 3 months (mean diff, -12.3) compared with controls. In modeling, treatment group (Centering or control) and educational levels were both associated with all the outcomes of interest. Beyond 6 months, there were too few participants for meaningful analyses. Conclusion(s): Women with ICBPS participating in a Centering group have, in the short term, less pain, pain interference, and ICBPS-specific symptoms than patients with usual care alone. Larger studies with more follow-up are needed to determine if this treatment effect extends over time.Copyright © 2022 American Urogynecologic Society. All rights reserved.

Urinary Tract Infections: Virus

Although viruses are common in the urinary tract in healthy people, viral infections can become a major concern in immunocompromised individuals. Patients undergoing hematopoietic stem cell or solid organ transplantation may be particularly susceptible to BK and other viruses, and experience a high risk of mortality. The most common presentation in this setting is hemorrhagic cystitis. The treatment is mostly supportive, including the reduction of immunosuppression;a variety of experimental agents has also been proposed. A different context is offered by chronic (HBV, HCV, HIV) or acute/subacute (Dengue, Hantavirus, etc.) infections, where the kidneys can be secondarily involved and suffer from several glomerular syndromes. Many protocols based on different oral direct-acting antivirals and combined antiretrovirals are available, according to the systemic infection. Viral infections can be classified according to the organ involved, i.e. lower (bladder) or upper urinary tract (kidneys, ureters), and to the mechanism of injury. A section is dedicated to the current breakout of SARS-CoV-2, which does not spare the urinary tract, sometimes with serious implications. Even if this topic is mostly the discipline of ultra-dedicated physicians, this overview has a practical approach and could be useful to a wider medical audience, especially in times of viral pandemics. © 2022 Elsevier Inc. All rights reserved.

Covid-19 Fatigue: Diagnosis and Treatment for the Osteopathic Physician

The novel coronavirus disease 2019 (COVID-19) has given rise to a global pandemic, as well as a multitude of long-term sequelae that continue to perplex physicians around the world, including in the United States. Among the most common and impactful long-haul symptoms experienced by survivors is COVID-19 fatigue. This review will use long COVID-19, post-acute COVID-19 syndrome (PCS), and PostAcute Sequelae of COVID-19 (PASC) as synonymous terms to refer to the chronic symptomatology;chronic fatigue associated with PASC will be referred to as COVID-19 fatigue. While the knowledge and research on the exact pathophysiological mechanisms involved in the disease is still limited, parallels have been drawn between fatigue as a component of long COVID-19 and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). Current studies suggest applying principles of pathophysiology, diagnosis, and treatment similar to those for ME/CFS in order to aid in managing chronic fatigue in COVID-19 survivors, particularly in the primary care setting. The osteopathic family physician can use the proposed pharmacologic agents, along with osteopathic manipulative treatment (OMT), as therapeutic modalities that can be tailored to each patient's unique case. Nevertheless, research on proven successful treatments is still scarce. For that reason, it is essential that COVID-19 fatigue is recognized early, especially since its longitudinal impacts may be debilitating for many. This review of the available literature on COVID-19 fatigue aims to help provide quality care and lessen the disease burden experienced by patients.Copyright © 2023 by the American College of Osteopathic Family Physicians. All rights reserved.

The significance of coronavirus infection in the development of reproductive and lower urinary tract lesions.

The impact of COVID-19 on the organs of the genitourinary system is of particular interest to the urologist. There is insufficient information about this influence up to date. The studies are actively developing and require long-term data analysis to determine possible long-term complications, persistent changes in physiological parameters and anatomical and histological structures, as well as to establish the possibility of regression of these changes and complications. The results obtained will undoubtedly improve not only the diagnosis, treatment and prevention of coronavirus infection and its complications, but also make it possible to predict certain disease's outcomes and changes in the function of organs and systems. In turn, this will give an understanding of the measures that need to be taken to completely avoid or minimize these complications and changes. This review focuses on the impact of COVID-19 on genitourinary organs, particularly its place in the development of the lower urinary tract and reproductive organs lesions, as well as the role of androgens in the course of SARS-CoV-2.Copyright © 2021 Vestnik Urologii. All rights reserved.

Toxicity patterns associated with chronic ketamine exposure

Introduction: Synthesized in 1962, ketamine is used as a sedative, antidepressant and for the management of complex chronic pain. More recently, besides its therapeutic use, ketamine has been increasingly used as a recreational drug among young adults. As a result, an increasing number of reports have described side effects associated with its chronic exposure. This review aims to present the current evidence on the toxicity associated with chronic ketamine exposure. Method(s): Considering the limited literature on the topic, Pubmed and Embase were searched and all types of articles were considered, including systematic reviews, retrospective studies, case series and animal studies. Evidence: Chronic ketamine exposure is associated with urological toxicity manifesting mainly by lower urinary tract symptoms with features of ulcerative cystitis. More severe forms with upper urinary tract involvement can require multiple line treatments, including surgery. There are reports of gastrointestinal toxicity with abdominal pain, liver function test derangement and cholangiopathy. More recently, reports have described the association between prolonged ketamine sedation during covid-19 outbreak and cholangiopathies. Development of tolerance, brain and psychiatric changes have been described. These can manifest in cognitive impairment and psychiatric disorders, with schizophrenia-like symptoms. Possible cardiovascular alterations have been described in few reports. Whereas supportive treatment can offer transient relief, ketamine cessation remains the cornerstone of the treatment. Conclusion(s): There is evidence of toxicity associated with chronic ketamine exposure on the different systems studied in this review. Nevertheless, due to the limitation of the studies more prospective studies would be required to clarify those findings.Copyright © 2023 Societe Francaise de Toxicologie Analytique

Management of Acute Cystitis in the Era of COVID-19.

Purpose of Review: No specific guidelines have been developed for acute cystitis management during the COVID-19 pandemic. This review aims to provide up-to-date information about treatment and follow-up in patients with symptoms suggesting lower urinary tract infection. Recent Findings: Uncomplicated cystitis does not need microbiological confirmation; thus, clinical diagnosis via telephone interview or questionnaires may be done. When complicated infections are suspected, in-person evaluation or close follow-up is mandatory. Antibiotic treatment is still the gold standard for treatment, although non-pharmacological strategies have also been suggested and further investigations are warranted. Summary: Urinary tract infections are still a frequent reason for consultation that needs to be addressed in both primary care and specialized levels. Their management during the pandemic is similar than in precedent years, but telehealth options have emerged which can facilitate diagnosis and treatment.

Association between the COVID-19 global pandemic and the prevalence of cats presenting with urethral obstruction at two university veterinary emergency rooms.

OBJECTIVES: The aim of this study was to investigate a potential association between the COVID-19 pandemic stay-at-home orders and the prevalence of emergency room presentations for urethral obstruction (UO) in feline patients. METHODS: Medical records and hospital census were retrospectively searched to identify the total number of cats and total number of male cats with UO presenting to two academic veterinary medical centers from 22 March to 10 August in the years 2018 (123), 2019 (137) and 2020 (175). Cats were grouped based on the year of presentation and the proportions of UO cases relative to all cats presenting to the emergency rooms during the same time frame. Absolute (year of interest - reference year) and relative ([year of interest - reference year]/[reference year]) change in prevalence was determined. These were compared for each year using a two-sample z-test. RESULTS: The absolute and relative prevalence of UO presentations across the combined population increased significantly during the COVID-19 pandemic in comparison with 2018 (2.2% and 59%, respectively; P = 0.0003) and 2019 (1.9% and 48%, respectively; P = 0.0021). For the individual institutions, a significant increase in UO presentations was found for institution A when comparing 2020 with both 2018 (P = 0.0072) and 2019 (P = 0.0073), but not for institution B (P = 0.057 and P = 0.18, respectively). No significant differences were found when 2018 and 2019 were compared across the combined population or within institutions. CONCLUSIONS AND RELEVANCE: The results of this study demonstrate an increased prevalence of UO during the initial months of the COVID-19 pandemic, which may be related to environmental change and stress imposed by stay-at-home orders.

Complete response to eculizumab in atypical hemolytic uremic syndrome with homozygous C3 mutation

Case Report: Atypical Hemolytic Uremic Syndrome (atypical HUS) is a rare and severe form of thrombotic microangiopathy (TMA) characterized by thrombocytopenia, intravascular hemolysis, and acute kidney injury with an incidence of 1 per million.1 Dysregulation and overactivation of the complement alternative pathway due to genetic mutations have been detected in 40-60% of patients with sporadic or familial atypical HUS.2,4 Triggers include viral illness, pregnancy, malignancy, sepsis, or sporadically with no known inciting event.1 Atypical HUS is a severe disease with a 2-10% risk of mortality, 33% risk of end-stage renal failure, and 50% chance of relapse.5 A 24-year-old female with prior history of atypical HUS at the age of 16 (with response to plasmapheresis) presented to the ER with a 5-day history of fever, chills, sore throat, nausea, vomiting, and dark urine. She tested positive for COVID-19. The exam revealed scleral icterus and scattered petechiae. Labs demonstrated nadir hemoglobin (Hgb) of 9.2 g/dL, platelet count of 52 000k/uL, haptoglobin < 30 mg/dL, peak LDH 1128U/L and creatinine 4.62 mg/dL. Urinalysis is consistent with hemoglobinuria. Schistocytes were noted on the peripheral smear. Rapid streptococcal antigen test and C3, C4, and IgA levels were unremarkable. Chest X-Ray, X-ray KUB, and ultrasound abdomen were unremarkable. The pregnancy test was negative. ADAMTS13 was >100%. Genetic analysis after the initial episode at age 16 revealed autosomal recessive inheritance c.193A > c gene mutations in C3. The patient received IV fluids, ceftriaxone for cystitis, and two units of Fresh Frozen Plasma. She initiated treatment with eculizumab. She also received the MENVEO and meningitis B vaccine per protocol due to the risk of meningitis from terminal complement deficiencies. After 4 infusions of eculizumab, patient's labs improved to platelet count of 307 000 k/uL, Hgb 12.2 g/ dL (nadir 9.2 g/dL), haptoglobin 78 mg/dL normalization of LDH and improved creatinine. Atypical HUS is a rare form of TMAwith mutations in C3 noted in 5% of cases. Complement cascade dysfunction leads to endothelial deposits and microvasculature damage. The resulting prothrombotic state causes obstructive microvascular thrombi predominantly affecting the kidneys but can cause multiorgan dysfunction. The SARS-CoV-2 virus may precipitate atypical HUS relapse due to endothelial damage and complement activation further intensified in patients with existing complement aberrations. Plasma exchange remains a standard of care for atypical HUS, as it effectively removes the antibodies and other proteins. Eculizumab a humanized monoclonal IgG antibody binds to complement proteins, preventing cleavage into C5a and C5b blocking C5b-9(MAC) activation. In patients with CFH, CFI, C3, and CFB mutations, eculizumab is the preferred intervention. Copyright © 2023 Southern Society for Clinical Investigation.

Reduced Duration Intracavitary Brachytherapy in Cervix Malignancies: A Comparative Analysis from Single Institute

Purpose: The on-going pandemic has impacted the use of anesthesia and the operating room frequency thereby affecting the brachytherapy treatment in various institutions due to the COVID-19 protocols. This has led to single applications of Intracavitary brachytherapy (ICRT) being used to deliver entire treatment boost in cervix cancer. We present our dosimetric and early clinical outcomes comparing traditional weekly three-fractions ICRT with single application/ two-applications ICRT Material(s) and Method(s): In this retrospective analysis conducted in our department, a total of 39 cases, treated between January 2021 to January 2022 were evaluated for the study. Of these, 15 cases were treated with the traditional once a week applicator insertion for 3 fractions and 24 cases underwent lesser application - 20 cases underwent 2 insertions and 4 cases single insertion (all receiving total 3 fractions of 7Gy each). The dosimetric parameters were compared including CTV D90 and D95 along with rectum, sigmoid and bladder D2cc, 1cc and 0.1cc respectively. The acute toxicity assessment was done using the RTOG scale. The follow-up was undertaken as per the institutional protocol and Mann-Whitney U-test were applied to compare the cohorts. Result(s): With a median follow-up of 6 months, the median CTV was D90%: 81.2 vs. 80.9 Gy and the median CTV volume was 44.3 vs 42.9 cc respectively. The 0.1 cm3 and 2 cm3 to bladder, rectum, and sigmoid were 105.6 vs 104.2 Gy and 85.5 vs 85.9Gy, 89.4Gy vs 88.7Gy and 69.1 vs 67.8Gy, and 84.7 vs 84.1Gy and 71.7 vs 69.9Gy, respectively suggesting no significant difference in the dosimetric outcomes with the two forms of applications. The less than three applications had a shorter overall treatment time with median OTT of 43 days vs. 55 days (p = 0.02). On completion of treatment and 6 months follow-up, local control was achieved in all patients. There was no significant difference in the acute toxicities in terms of cystitis and proctitis in both forms of the application. Conclusion(s): The single application/ twice application ICRT procedure showed similar outcomes as the traditional three-week duration treatment in terms of dosimetric outcomes and acute toxicities and ultimately leading to shortened overall treatment time. It also helped reduce the anesthesia burden and various resources associated with the procedure. Copyright © 2022

Patient Engagement in Management of Recurrent Urinary Tract Infections

Purpose of Review: Recurrent urinary tract infections (rUTIs) are highly prevalent among women and can be challenging to manage for both clinicians and patients. This review aims to outline and analyze important studies relevant to clinical care and provide patient-centered recommendations. Recent Findings: The current literature supports that the treatment of rUTIs is multifaceted, and improving patient engagement requires clinical strategies that prioritize improving women's quality of life. Culture-directed treatment of recurrent infections to prevent collateral damage from antibiotics is supported by the 2019 Recurrent Uncomplicated Urinary Tract Infections in Women Guidelines published by the American Urological Association, Canadian Urology Association, and Society of Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction. Qualitative studies have identified important considerations for patients such as antibiotic and non-antibiotic treatment options, financial costs, as well as physical and mental health impairments. Summary: Solely treating the physical symptoms caused by recurrent urinary tract infections without discussing prevention strategies and quality of life challenges caused by rUTIs will likely lead to poor patient engagement and satisfaction. Building a medical practice with ancillary physician support to expedite and increase convenience may help meet patient expectations and ease the burden of care identified in prior studies. Physicians should prioritize antibiotic stewardship and be mindful that microbiome research has demonstrated that healthy bladders have been found to have commensal bacteria, which may act as barriers against uropathogens, thus helping prevent urinary tract infections. Copyright © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Prescription of Choreito, a Japanese Kampo Medicine, with Antimicrobials for Treatment of Acute Cystitis: A Retrospective Cohort Study.

Choreito, a Japanese Kampo medicine, is used to treat Japanese female patients for the quick relief of inflammatory symptoms associated with acute cystitis. We evaluated whether Choreito is effective in reducing antibiotic use and the number of clinic visits for these patients. Females aged 18-49 years who had acute cystitis for the first time, with no history of medical insurance use within 90 days prior to their visit, and no hospitalizations within the 30 days after their first visit were identified from the JMDC Claims Database between April 2018 and March 2021. For the 30 days after their first visit, patients who were given their first antimicrobial prescriptions with or without Choreito were compared regarding (i) the number of clinic visits, (ii) total antimicrobial prescription days, and (iii) the number of antimicrobial prescriptions adjusted for their age, Charlson comorbidity index, and the COVID-19 pandemic period (after April 2020). For the 319 and 8515 patients with or without a Choreito prescription, respectively, multivariable Poisson regression analyses showed that Choreito was significantly associated with a 5% shortening of a patient's total antimicrobial prescription days (Beta, 0.950; p = 0.038), whereas no significant difference was observed in the number of clinic visits and antimicrobial prescriptions (p = 0.624 and p = 0.732, respectively). The prescription of Choreito in combination with antimicrobials was associated with a slight reduction in total antimicrobial use for acute cystitis among females.

Safety and clinical efficacy outcomes from the Long-term extension study of tolebrutinib in patients with relapsing multiple sclerosis: 2-year results

Introduction: Phase 2b trial (NCT03889639) findings in patients with relapsing multiple sclerosis showed central nervous systempenetrant Bruton's tyrosine kinase inhibitor tolebrutinib was well tolerated over 12 weeks and elicited dose-dependent reductions in new gadolinium-enhancing T1 and new/enlarging T2 lesions. Objective/Aim: To characterise tolebrutinib's safety and efficacy at Week 96 (2 years) in the phase 2b trial's long-term safety (LTS) extension (NCT03996291). Method(s): In LTS extension Part A, patients continued their core study tolebrutinib dose (5, 15, 30, or 60 mg/day) double-blind until the phase 3 study dose selection (60 mg/day). In Part B, patients received open-label tolebrutinib 60 mg/day. Safety was assessed via adverse event (AE) reporting. Efficacy outcomes included annualised relapse rate (ARR) and change from baseline Expanded Disability Status Scale (EDSS) score. Result(s): 124 of 125 patients completed Part A and transitioned to Part B;114 (90.5%) remained on study as of 7 March 2022. One patient receiving tolebrutinib 5 mg/day discontinued Part A because of progressive disease and 10 discontinued Part B because of AEs (n=3), perceived lack of efficacy (n=4), emigration (n=2), and patient decision (n=1). At Week 96, no new safety signals have been observed. The most common treatment-emergent AEs (TEAEs) were COVID-19 (20.8% [26/125]), headache (13.6% [17/125]), nasopharyngitis and upper respiratory tract infection (both 11.2% [14/125]), bacterial cystitis (7.2% [9/125]), and pharyngitis and arthralgia (both 5.6% [7/125]). No tolebrutinib dose effects for TEAEs or serious AEs were observed in Part A and no safety signals emerged for patients switching to tolebrutinib 60 mg/day in Part B. Of those who received tolebrutinib 60 mg/day for a minimum of 8 weeks, ARR was 0.17 (95% CI: 0.12, 0.25) and 80.6% remained relapse-free. Mean EDSS remained stable to Week 96. Conclusion(s): Through LTS Week 96, tolebrutinib 60 mg/day continues to show favourable safety, and is associated with a low ARR and stable disability status.

Florid cystitis cystica et glandularis mimicking a bladder tumour: A rare case report

Background: An 80 years old male patient presented with urinary retention. He had lower urinary tract symptoms for the last two years. The patient was catheterized and subsequently developed gross hematuria. The patient was COVID- 19 positive. Method(s): The ultrasonography showed bladder wall thickening with bladder mass around the neck. The computerized tomography scan showed heterogeneously enhancing thickening in the left lateral wall of the urinary bladder and was suspected to be neoplastic. There was a suspicious heterogeneously enhancing lesion in the base of the prostate. His serum prostate-specific antigen level was 5.79 ng/ml. His repeated urine cytology for malignant cells was non-diagnostic. Result(s): The patient underwent transurethral resection of bladder tumour (TURBT) and transurethral resection of the prostate (TURPT). The TURBT biopsy showed florid cystitis cystica et glandularis and the TURPT biopsy showed adenomatous hyperplasia. Conclusion(s): The florid cystitis cystica et glandularis mimic a malignancy, and it is, therefore, important to consider it as a differential diagnosis while evaluating catheterized patients with lower urinary tract symptoms.