Additional Therapy Research Articles

Adjuvant local antibiotic therapy in the management of diabetic foot osteomyelitis

BackgroundThe management of diabetic foot osteomyelitis (DFO) is complex. The targeted use of adjuvant local antibiotics, in the form of biocomposite bone void filler, in DFO, can enhance patient outcomes while minimising the adverse effects associated with systemic antibiotic therapy and its shortcomings.MethodsWe reviewed a series of 105 consecutive patients who underwent surgical management for diabetic foot osteomyelitis. In the NLAB group, (no adjuvant local antibiotic use), 49 patients, received the current standard of care treatment with no use of adjunctive local antibiotic therapy. In group LAB, (adjuvant use of local antibiotics), 56 patients received additional adjuvant local antibiotic therapy. Patient outcomes were compared between both groups.ResultsInfection healing was demonstrated in 10 (20.41%) patients from group NLAB and 41 (73.21%) from group LAB (p < 0.0001). Persistence of infection with no evidence of wound healing, 6 months from surgery, was observed in 15 (30.61%) patients in group NLAB. Among the LAB group, only 4 (7.14%) patients demonstrated infection persistence (p = 0.00183). Reinfection was observed in 24 of 49 patients in group NLAB (49%) and in only 11 out of 56 patients in group LAB (20%) (p = 0.001466). 7 (6.67%) patients required major amputation with 6 (12.24%) belonging to group NLAB. Only 1 (1.78%) patient in group LAB underwent major amputation. A higher 5-year mortality rate was noted within patients in group NLAB, 27 (55.1%). The mortality rate in group LAB was (12.5%).ConclusionThe adjuvant use of antibiotic loaded bio-composite bone void filler locally was associated with increased infection clearance rates regarding diabetic foot osteomyelitis when compared with the standard care of treatment while achieving lower rates of infection persistence and recurrence. It also has the potential to reduce amputation and mortality rates with further research.

Lentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-in-Human Trial.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Although CF is a multiorgan disease, the leading causes of morbidity and mortality are related to progressive lung disease. Current understanding of the effects of the broad spectrum of CFTR mutations on CFTR function has allowed for the development of CFTR modulator therapies. Despite the remarkable impact that these therapies have had, there remains a significant proportion of people with CF (estimated at 10-15% of the global CF population) who are genetically ineligible for, or intolerant of, current CFTR-targeting therapies and whose therapeutic needs remain unmet. Inhaled genetic therapies offer the prospect of addressing the unmet pulmonary treatment need in people with CF, with several approaches, including gene addition therapy (the focus of this review), RNA-based therapies, antisense oligonucleotides, and gene editing, being explored. Various nonviral and viral vectors have been investigated for CF gene addition therapy for mutation-agnostic restoration of CFTR function in the lungs. Lentiviral vectors offer the prospect of highly efficient and long-lasting gene expression, and the potential to be safely and, in contrast to other commonly used viral vectors, effectively redosed. A third-generation lentiviral vector pseudotyped with Sendai virus F and HN envelope proteins (rSIV.F/HN) has been developed for the treatment of CF. Promising preclinical results support the progression of this vector carrying a full-length CFTR transgene (BI 3720931) into a first-in-human clinical trial expected to begin in 2024.

Prolonged corticosteroid therapy and lung abnormalities in patients after severe COVID-19 pneumonia.

Some of the hospitalized patients after severe COVID-19 pneumonia experience significant fall in peripheral saturation despite optimal treatment. Because of immune dysregulation in COVID-19 there are indications that prolonged corticosteroids could be considered in treating patients for persistent radiological sequelae and respiratory symptoms. to investigate lung function and lung sequelae on high-resolution CT (HRCT) im COVID-19 patients who were treated with glucocorticoid therapy in two dose regimens with a control group of patients who did not receive additional glucocorticoid therapy. In this prospective cohort research we studied patients who suffered from prolonged respiratory insufficiency after severe COVID-19 pneumonia. Patients received corticosteroid therapy in two dose regimens: for 14 days and for 3 months after discharge from the hospital. Control group of patients did not receive additional corticosteroid therapy. Lung function, post-COVID-19 symptoms, and lung abnormalities on CT scans were analyzed in three months follow-up and compared with the control group of patients. Patients who received prolonged corticosteroid therapy for three months did not have better CT findings of lung abnormalities, lung function, or symptoms recovery in comparison to the patients with 14 days of therapy and control group of patients. Onwards, control group had significantly fewer dyspnea symptoms (Chi-square test, p=0,04) and higher DLCO (Kruskal Wallis test, p=0,03). Supplementary corticosteroid therapy for patients after severe pneumonia and prolonged respiratory insufficiency with lung abnormalities after COVID-19 did not improve lung function or lung lesions on CT.

Stent retriever expansion as a corrective maneuver to optimize inadequately deployed flow diverter stents.

As flow diversion (FD) is becoming increasingly important in the endovascular treatment of intracranial aneurysms, the rate of technical complications is also increasing. Inadequate FD implantation may lead to both ischemic complications and decreased treatment efficacy. The aim of this study was to evaluate the efficacy of off-label stent retriever (SR) use in managing technical complications associated with FD implantation. A retrospective analysis of data from patients who underwent FD treatment at two neuroradiology centers was performed. The objective was to identify cases in which the FD was inadequately deployed and SR expansion was performed as a corrective maneuver. The analysis included anatomic characteristics, technical information, angiographic and clinical outcomes, and complications. A total of 35 corrective maneuvers with SR were performed in 25 FD treatments. The corrective maneuvers in all treatments were successful, and no additional devices or therapies were required. No procedural complications or technical difficulties were documented. With the growing role of FDs in neurointerventional treatment, familiarity with corrective maneuvers after technical complications or inadequate implantation is important. The findings in our selected cohort demonstrated that SR expansion is an effective and safe corrective maneuver for incompletely opened FDs.

Metachronous metastasis of papillary thyroid carcinoma to the parotid gland: a case report and review of the literature.

We present a case of metachronous metastasis of papillary thyroid carcinoma to the parotid gland, this being an extremely rare metastasis, and a literature review. A 56-year-old female patient presented with a history of a slowly growing mass on the left side of the neck. The patient reported a medical history of thyroidectomy due to papillary thyroid carcinoma 23 years previously and neck dissection for lymph node metastases 10 years previously, with additional therapy using radioactive iodine in both cases. Computed tomography (CT) of the neck revealed a single nodular solid mass in the tail of the left parotid gland which showed heterogeneous intake of contrast agent. FNA biopsy of the left parotid gland revealed cells typical of papillary thyroid carcinoma with positive immunochemistry for TTF-1. Due to this new metastasis, a total parotidectomy with preservation of the facial nerve was performed and additional therapy with radioactive iodine was administered. Despite the fact that papillary thyroid carcinoma has a low incidence of regional and distant metastases, there are a few rare cases with distant metastases reported in the literature. Thus, awareness, especially among endocrinologists, and a multidisciplinary approach are crucial to ensure early detection and efficient treatment of these rare cases, distant metastases being the main cause of mortality and of reduction of overall survival rate among these patients.

The Use, Profile, Uptake, Characteristics and Attributes of Users of Homeopathy: Initial Findings from a Student Teaching Tele-Healthcare Clinic Based in North America

Research into the uptake profile and usage of Homeopathy has hitherto tended to be buried amongst complementary medicine research. Despite high levels of uptake of homeopathy, and robust numbers of over-the-counter sales of homeopathic products the current evidence evaluating the uptake of homeopathy remains limited on several fronts. The aim of this study is to explore the basic demographic features and characteristics of users of homeopathy services. The setting is a student teaching tele-health facility based in NA. Concurrent intake forms from 303 participants were analyzed. Intake forms were entered into a coding frame instrument designed and developed to explore health care information. A majority of participants (70%) who attend this clinic are female. The average age is 31 years old. Almost half of the participants in this clinic were using other additional complementary therapies in the management of their conditions. Almost the same number of participants (134) were only using homeopathy. The majority had some prior use of homeopathic products (91.6%), but 52.8% of participants had never worked with a professional homeopath. Twenty-four conditions are listed by participants as chief health complaints. Findings are in alignment with what is already known about the uptake in complementary medicine. Findings also reveal that the users of Homeopathy are seeking an ‘alternative’ to conventional medicine rather than only using Homeopathy as ‘complementary’ medicine. A proportion of participants in this clinical setting find homeopathy through over-the-counter sales and are, for a period, self-prescribing in chronic conditions. Further comparative research is needed to compare this to other complementary medicine avenues as well as conventional medicine settings. Conclusion: This in-depth empirical study of the users of homeopathy at one clinical facility represents initial, novel measured preliminary insights into the participants features and characteristics.

Emerging paradigm: Molecularly targeted therapy with Dabrafenib and Trametinib in recurring pediatric gliomas with BRAF mutations: A narrative review.

Gliomas are tumors arising in the central nervous system, frequently associated with Class I mutations and BRAF fusions. These mutations are adverse prognostic factors in juvenile gliomas, leading to high rates of recurrence and poor response to current treatments. The blood-brain barrier and the heterogeneity of gliomas complicate the development of a single treatment strategy for all cases. This review aims to evaluate the efficacy and safety of combination therapies, particularly Dabrafenib and Trametinib, in pediatric gliomas with BRAF V600 mutations and discusses their potential in improving clinical outcomes. A review of recent clinical trials was conducted to assess the impact of targeted therapies, especially the combination of Dabrafenib and Trametinib, on glioma treatment outcomes. Additional therapies are also explored. Combination therapy with Dabrafenib, a BRAF kinase inhibitor, and Trametinib, a MEK inhibitor, has shown significant improvement in overall survival and progression-free survival for pediatric patients with BRAF V600-mutant gliomas. Recent clinical data from 2023 demonstrated enhanced tumor control, reduced relapse rates, and improved safety profiles compared to conventional therapies. Dabrafenib and Trametinib offer a promising targeted therapy for juvenile gliomas with BRAF V600 mutations, with better survival outcomes and manageable safety profiles. However, challenges remain in managing side effects such as fever, headache, lethargy, and rash. Further research into resistance mechanisms and long-term effects is necessary to optimize treatment strategies. Other therapies, such as everolimus and Selumetinib, also show potential and warrant further investigation.

Same-Day Discharge After Uncomplicated Transcatheter Tricuspid Valve-In-Valve Implantation.

Tricuspid valve-in-valve (TVIV) implantation has traditionally included post-procedure overnight in-hospital observation with next-day discharge. Recently, our practice has shifted toward same-day discharge for most patients after vascular access site hemostasis and adequate recovery from anesthesia. However, data on the safety of this approach remains scarce. Our study aims to describe our practice change and to identify factors that may lead to overnight observation post-TVIV. We retrospectively reviewed medical records of patients who underwent uncomplicated TVIV implantation as an outpatient procedure at Mayo Clinic between 2011 and 2023. Of the 83 patients who underwent TVIV from 2011 to 2023, 65 (78%) were included in the study. The first 39 patients in our institutional series were observed overnight as standard practice. 18 (69%) of the most recent 26 patients in our series were discharged the same day; three patients who remained in the hospital overnight were because of provider preference and/or patient preference without any specific medical concern. Of all 47 patients who were observed overnight, one patient was treated for fluid overload, one patient had non-sustained ventricular tachycardia on telemetry that resulted in adjustment of antiarrhythmic therapy, two patients had continued bleeding from the access sites and was observed for another day. Among the two of them, one also developed atrial tachyarrhythmias requiring initiation of additional antiarrhythmic therapy. Out of 18 patients discharged the same day, one patient had an ED presentation within 24 h due to access site bleeding which was resolved promptly. There was no mortality or procedural-related readmission. Same-day discharge may be considered for adult patients who have undergone uncomplicated TVIV with adequate hemostasis and recovery after anesthesia.

Mass-forming intrahepatic cholangiocarcinoma: treatment outcomes after curative-intent resection in an Australian tertiary referral hospital.

Mass-forming intrahepatic cholangiocarcinoma (MF-ICC) is the second most common primary liver cancer and liver resection offers the best chance of possible cure. This study aimed to assess treatment outcomes and prognostic factors for long-term survival in patients who underwent curative-intent liver resection. A retrospective analysis was conducted on prospectively collected data from patients with MF-ICC managed at the Royal North Shore/North Shore Private Hospital from January 1998 to October 2023. Baseline, peri-operative and long-term outcomes have been analysed, including an overall survival (OS) and disease-free survival (DFS) analysis. During the 25-year study period, 47 patients underwent curative-intent liver resection for primary MF-ICC at a median age of 70 years. The median OS was 36 months, with a 5-year OS of 33%. Multiple liver tumours (HR = 2.84; 95% CI = 1.24-6.48; P = 0.013) and a positive resection margin (HR = 2.46; 95% CI = 1.10-5.52; P = 0.029) were identified as independent predictors of poor long-term OS. Recurrence occurred in 62% of patients after a median DFS of 16 months, with poor tumour differentiation (HR = 3.93; 95% CI = 1.62-9.54; P = 0.002) and elevated tumour markers (HR = 3.47; 95% CI = 1.53-7.87; P = 0.003) as independent predictors of poor DFS. Liver resection can offer a significant chance for prolonged survival in a highly selected population of patients with MF-ICC. However, the surgical challenges inherent in treating this rare disease are evident, emphasizing the need for a multimodal approach and continued exploration of additional therapies to enhance personalized treatment strategies.

Endoscopic papillectomy versus surgical ampullectomy for adenomas and early cancers of the papilla: a retrospective Pancreas2000/European Pancreatic Club analysis

ObjectiveAmpullary neoplastic lesions can be resected by endoscopic papillectomy (EP) or transduodenal surgical ampullectomy (TSA) while pancreaticoduodenectomy is reserved for more advanced lesions. We present the largest retrospective comparative study...

Medication therapy problems detected at community pharmacy INR checks

Background: Despite the shift towards direct-acting anticoagulants, warfarin remains widely used in Canada and is traditionally managed by family physicians through laboratory-based international normalized ratio (INR) testing. The Community Pharmacy Anticoagulation Management Service (CPAMS) in Nova Scotia represents an innovative approach, enabling community pharmacists to conduct point-of-care (POC) INR testing and manage warfarin therapy. A potential benefit of this approach is the opportunity to identify non-warfarin medication therapy problems (nwMTPs) during routine visits. Method: We conducted a prospective, multicentre, observational study across 40 community pharmacies in Nova Scotia, part of CPAMS’s second phase. Pharmacists documented nwMTPs identified in patients with atrial fibrillation during routine POC INR visits using the Qualtrics Insight Platform, categorizing them by indication, effectiveness, safety, or adherence, alongside corresponding interventions. Results: Over 6 months, 43 nwMTPs were submitted from 13 unique pharmacies. There were 3404 POC INR tests in patients with atrial fibrillation, yielding an estimated nwMTP detection rate of 1.26 (95% CI, 0.69 to 2.32) per 100 INR tests. The most common nwMTP category was “Indication,” primarily requiring additional therapy. Pharmacists frequently intervened by recommending medication adjustments or providing patient education. Discussion: The findings highlight a modest, yet potentially significant role of pharmacists in detecting and managing diverse MTPs during focused warfarin management assessments. The predominance of indication-related problems underscores unmet therapeutic needs in patients on warfarin. Conclusion: This study illustrates the potential of pharmacist-led POC INR testing in community settings to identify and address nwMTPs, contributing to comprehensive patient care.

A phase I study of romidepsin in combination with gemcitabine, oxaliplatin, and dexamethasone in patients with relapsed or refractory aggressive lymphomas enriched for T-cell lymphomas.

Histone deacetylase inhibitors (HDACi) and combination chemotherapy are independently used to treat relapsed/refractory (R/R) lymphoma. In vitro studies suggest that the addition of HDACi to platinum-based chemotherapy is synergistic. We conducted a phase I study of romidepsin, gemcitabine, oxaliplatin and dexamethasone (Romi-GemOxD) in R/R aggressive lymphomas with an expansion cohort in T-cell lymphomas. Twenty-four patients were enrolled with median age 70; 6 patients had diffuse large B-cell lymphoma (DLBCL) and 18 patients had peripheral T-cell lymphomas (PTCL-NOS: 10, angioimmunoblastic T-cell lymphoma [AITL]: 7, ALK-negative anaplastic large cell lymphoma: 1). Patients had received a median of 2 prior lines of therapy and 10 patients were refractory to last line of therapy. Using a standard 3+3 dose escalation design, the maximum tolerated dose of romidepsin was determined to be 10 mg/m2 in combination with GemOxD. There were no unexpected toxicities. The most common grade ≥3 treatment-emergent adverse events were thrombocytopenia (79%) and lymphopenia (46%). The overall response rate for Romi-GemOxD was 52% (12/23) with complete response (CR) rate of 43% (10/23). All six patients with AITL evaluable for efficacy achieved CR. Durable responses were seen in patients with AITL, PTCL-NOS and DLBCL. Without additional therapy, four patients remained in remission for more than two years, with three patients progressing at 46.5, 30.8, and 32.6 months and one remission ongoing at 83 months. Four patients proceeded to consolidative stem cell transplant following induction. Romi-GemOxD represents a well-tolerated, time-limited, effective option for patients, particularly for those with AITL in which durable responses were seen. NCT02181218Micro Abstract: In a phase I study of romidepsin in combination with gemcitabine, oxaliplatin and dexamethasone in patients with relapsed/refractory aggressive lymphomas, the maximum tolerated dose of romidepsin was 10 mg/m2. The complete response rate in patients with angioimmunoblastic T-cell lymphoma was 100% (6/6) with median duration of response of 28.9 months. This salvage option warrants further consideration, especially in T-cell lymphomas.

Drug-Resistant Epilepsy and Gut-Brain Axis: an Overview of a New Strategy for Treatment.

Drug-resistant epilepsy (DRE), also known as intractable epilepsy or refractory epilepsy, is a disease state with long-term poorly controlled seizures attack. Without effective treatment, patients are at an elevated risk of injury, premature death, mental disorders, and poor quality of life, increasing the need for a fresh perspective on the etiology and treatment of DRE. The gut is known to harbor a wide variety of microorganisms that can regulate the host's response to exogenous signals and participate in various physiological and pathological processes in the human body. Interestingly, emerging evidence has uncovered the changes in gut microbiota in patients with epilepsy, particularly those with DRE. In addition, both dietary interventions and specific antibiotic therapy have been proven to be effective in restoring the microecological environment and, more importantly, reducing seizures. Here, we reviewed recent studies on DRE and the involvement of gut microbiota in it, describing changes in the gut microflora composition in patients with DRE and corresponding animal models. Furthermore, the influence of the ketogenic diet, probiotics, fecal microbiota transplantation (FMT), and antibiotics as microbiome-related factors on seizure control and its possible mechanisms are broadly discussed. Finally, we highlighted the significance of gut microbiome in DRE, in order to provide a new prospect for early identification and individualized treatment of patients with DRE.

Efficacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the D-A-CH-region: a population-based observational study

Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0-90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n=16, nusinersen: n=154, both: n=2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

Novel Therapies in the Perioperative Management of Localized Gastric Cancer: Current Perspectives and Future Directions

The management of localized gastric cancer has evolved considerably with the advent of novel perioperative treatment strategies with chemotherapy, significantly impacting patient outcomes. Traditionally, surgery has been the cornerstone of treatment, but recurrence rates remained high, necessitating the exploration of additional therapies to enhance long-term survival. The interplay between chemotherapy and radiotherapy is being meticulously studied to define the optimal sequencing and combination that maximizes tumor control while minimizing toxicity. Furthermore, the integration of targeted therapies and immunotherapy into the perioperative setting is gaining momentum with agents targeting HER2, VEGF, and PD-1/PD-L1, pathways have shown promise in advanced gastric cancer and are now being tested in the neoadjuvant and adjuvant settings. Preliminary results from trials investigating these agents, such as pembrolizumab and trastuzumab-deruxtecan, suggest potential survival benefits and warrant further exploration in combination with chemotherapy in the perioperative context. Additionally, the heterogeneity of gastric cancer across different populations and geographic regions necessitates tailored approaches that consider genetic and molecular characteristics of tumors, as well as patient comorbidities. This Comment provides a comprehensive overview of the latest therapeutic advancements in the perioperative setting for localized gastric cancer, emphasizing the critical role of multimodal treatment approaches.

Outcomes of the Subsequent Periprosthetic Joint Infection Revisions after a Failed Debridement, Antibiotics and Implant Retention: A Multicentric Study of 197 Patients.

Background: The impact of prior unsuccessful debridement, antibiotics, and implant retention (DAIR) procedures on subsequent revisions is uncertain, with conflicting evidence. Despite 85% consensus against the second DAIR procedure following the 2018 International Consensus Meeting, a 2020 study reported high success rates for the aforementioned second DAIR procedure. Methods: We conducted a multicenter observational study reviewing data from patients with failed DAIR procedures between 2005 and 2021. Patients diagnosed with acute periprosthetic joint infection of the hip or knee were included, following ICM criteria. Failure was defined as uncontrolled infection leading to additional surgeries, prosthesis removal, infection-related mortality, or suppressive antibiotic therapy. Demographic, surgical, and microbiological variables were recorded. Results: Among 197 patients from 10 institutions with failed DAIR procedures were included: 88 (44.7%) received a second DAIR, 21 (10.7%) underwent one-stage revision, and 77 (39.1%) underwent two-stage revision. One-stage revision success rate was 76.2%, with no identified predictors of failure. Two-stage revision success rate was 79.3%; factors associated with failure included polymicrobial infections (p = 0.025) and revision procedures (p = 0.049). Second DAIR success rate was 54.5%; factors associated with failure included non-specialized surgical teams in the first DAIR (p = 0.034), non-exchange of mobile components (p = 0.0038), polymicrobial infections (p = 0.043), and antibiotic resistance (p = 0.035). Excluding patients with these risk factors increased the success rate to 83.3%. Conclusions: Second DAIR's overall success rate was 54.5%, significantly increasing to 83.3% when excluding patients with identified risk factors. These findings suggest considering second DAIR in carefully selected patients without these risk factors. Our study found success rates of 76.2% and 79.3% for one- and two-stage revisions, respectively, aligning closely with published data.

Prostatectomy and other local treatments for oligometastatic prostate cancer: recent and ongoing trials.

Oligometastatic prostate cancer (OMPCa) is an intermediary state between localized and disseminated metastatic disease that has historically been treated with androgen deprivation therapy (ADT) and more recently with additional systemic therapies in combinations. However, cytoreductive control of the primary tumor may offer an opportunity to control the disease and enhance the response from systemic treatment. In this review, the use of local therapy to the prostate including cytoreductive prostatectomy (CRP), whole pelvis radiotherapy (RT), and focal therapies will be evaluated in the treatment of patients with newly diagnosed OMPCa. Retrospective studies have demonstrated that some patients with OMPCa may indeed benefit from CRP. With preliminary trials demonstrating that CRP is safe and feasible, there are several phase II and III trials that are currently underway to investigate the role of CRP among patients with OMPCa. Results from several clinical trials have demonstrated that RT and ADT may benefit patients with OMPCa. Lastly, the evidence for focal and cryotherapy remains limited and further clinical trials are required. OMPCa is a unique disease state that may benefit from local therapy to the primary tumor. Further study is required to guide treatment selection and patient candidacy. Several trials specifically are awaited to better define the treatment options for patients.

Childhood acute flaccid myelitis, including the first confirmed cases of enterovirus D68 myelitis, in Singapore and Southeast Asia.

We report the epidemiology, treatment and outcomes of acute flaccid myelitis (AFM), including the first two cases of enterovirus (EV) D68 myelitis, in Singapore. Retrospective observational study from a paediatric hospital in Singapore, from January 2012 to December 2022. Clinical, laboratory, neuroimaging and outcome data were analysed. Eight patients were identified (all male). Median age at presentation was 3 (interquartile range (IQR) 2.2-10.0) years. Seven (87.5%) patients were clustered in two time periods (July 2018-January 2019 and April-August 2022). Presenting features were a preceding febrile respiratory illness (n = 6) or hand-foot-and-mouth disease (n = 2), upper limb weakness (n = 5, 62.5%) and neurogenic bladder (3, 37.5%), while the spinal cord lesions were predominantly in the cervical region (7, 87.5%). Five (62.5%) and six (75.0%) patients had elevated cerebrospinal fluid (CSF) white cells (median 7.5/mm3 (IQR 2.8-40.3)) and protein (median 0.6 g/L (IQR 0.4-0.7)), respectively. CSF was negative for pathogens. Two (50%) of four patients with EV detected in respiratory/rectal swabs had EVD68 (2022 cluster). All received intravenous methylprednisolone, six (75%) had additional intravenous immunoglobulin and either plasma exchange therapy (n = 1) or intravenous tocilizumab (n = 1). Median modified Rankin Scale (mRS) at acute illness was 4 (IQR grades 3-5), with an improvement (median 2 (IQR 1.8-2.3) mRS grades) on follow-up (median duration 3.7 (IQR 1.4-4.1) years). One patient (12.5%) had a full recovery and seven (87.5%) have moderate disability (mRS 2-3). Disability risk in AFM is high despite aggressive immunotherapy. We report the first two confirmed cases of EV D68 AFM in Singapore and Southeast Asia.

Intratumoral Distribution of [177Lu]Lu-PSMA-617 Over Time and in Relation to Diagnostic Tracers in Animal Models of Prostate Cancer.

Introduction: Prostate-specific membrane antigen (PSMA) is a target for diagnostic positron emission tomography (PET)-tracers and radiopharmaceutical therapy (RPT), for example, [177Lu]Lu-PSMA-617, in prostate cancer. This autoradiography study investigates [177Lu]Lu-PSMA-617 intratumoral distribution over time, compared with PSMA expression, proliferation (Ki67), and [68Ga]Ga-PSMA-11, [18F]F-PSMA-1007, [18F]-fluorodeoxyglucose, and [18F]-fluorocholine distribution. Mice with LNCaP, 22Rv1, or PC-3 PIP xenografts got [177Lu]Lu-PSMA-617 i.v. Sacrificed 1 h p.i. if coinjected with diagnostic tracers, otherwise at 20 min, 1-2, 12, 24, 48, 72 h, or 2-3 weeks p.i. Cryosectioned tumors imaged by autoradiography, adjacent sections Ki67 or PSMA stained. Results: Heterogeneous distribution of [177Lu]Lu-PSMA-617 was seen 20 min p.i., with visible overlap between tumor cells, Ki67, PSMA, and radioactivity at 1-2 h p.i. Strongest Ki67-correlation at 48 h, which became negative at 72 h and beyond with some Ki67+/PSMA+ low radioactivity areas. Uptake in necrotic tissue was only observed at 2-3 weeks p.i. PSMA-targeted tracers distributed identically to [177Lu]Lu-PSMA-617 whereas other tracers only had some overlap. Conclusion: Regrowth of the tumor post-[177Lu]Lu-PSMA-617 administration creates Ki67+/PSMA+ areas that have no radioactivity uptake and need additional therapy fractions. The identical intratumoral distribution of [177Lu]Lu-PSMA-617 and PSMA-targeted PET-tracers indicate that these will reveal the areas inside the tumor targeted by RPT at least at 1 h p.i.

The Role of Neuromodulators and Deep Brain Stimulation (DBS) in the Treatment of Refractory Bipolar Disorder

Introduction: Refractory bipolar disorder is a complex psychiatric condition characterized by persistent manic and depressive episodes that do not respond adequately to conventional treatments, such as mood-stabilizing medications and antidepressants. This condition results in severe functional impairment, with a significant impact on patients' quality of life. Objective: To evaluate the role of neuromodulators and deep brain stimulation in the treatment of refractory bipolar disorder, analyzing their efficacy, mechanisms of action, and safety based on recent studies. Methodology: The research followed the PRISMA checklist guidelines for systematic reviews. Searches were performed in the PubMed, Scielo, and Web of Science databases, using the descriptors "refractory bipolar disorder", "deep brain stimulation", "neuromodulators", "treatment", and "therapeutic effects". The selection of articles was restricted to the last ten years. Inclusion criteria were: clinical studies on the use of DBS in refractory bipolar disorder, research investigating neuromodulators as additional therapies, and articles published in English, Portuguese or Spanish. Studies with small sample sizes, non-systematic reviews and articles that did not present relevant data on the therapeutic effects of these interventions were excluded. Results: The results indicated that both DBS and neuromodulators have shown to be promising therapies in the treatment of refractory bipolar disorder. DBS, especially when targeting the nucleus accumbens and other areas involved in emotional regulation, has been shown to reduce symptoms of mania and depression in several clinical studies. Neuromodulators, such as those affecting the dopaminergic and serotonergic systems, have also shown efficacy in some patients, but with less consistent results. Conclusion: Both deep brain stimulation and neuromodulators have shown potential in the treatment of refractory bipolar disorder, showing improvements in symptom control in patients resistant to conventional treatments. However, more long-term clinical studies are needed to consolidate the evidence of their efficacy and safety, in addition to optimizing treatment protocols.