Therapy Options Research Articles

Navigating Pediatric Cor Pulmonale: A Comprehensive Review of Diagnosis and Management.

Pediatric cor pulmonale, characterized by right ventricular dysfunction due to chronic pulmonary hypertension, presents significant diagnostic and management challenges. This comprehensive review delves into this complex condition's etiology, clinical presentation, diagnostic strategies, and management. Key etiological factors include congenital heart defects, chronic lung diseases, and pulmonary vascular disorders. Early diagnosis, facilitated by imaging, hemodynamic assessments, and laboratory investigations, is crucial for effective intervention. Pediatric cor pulmonale management encompasses pharmacological treatments, such as vasodilators, diuretics, and inotropic agents, and non-pharmacological interventions, including oxygen therapy, mechanical ventilation, and surgical options. Long-term follow-up is essential to monitor disease progression and adjust treatment strategies accordingly. Multidisciplinary care involving pediatric cardiologists, pulmonologists, and critical care specialists is paramount to address the multifaceted needs of these patients. The review highlights the importance of early recognition and comprehensive care, offering insights into current best practices and future research and clinical practice directions. Advances in understanding the pathophysiology of pediatric cor pulmonale and emerging therapies promise to improve patient outcomes, underscoring the need for continued collaboration and innovation in this field.

Iptacopan Efficacy and Safety to Treat Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Meta-Analysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon blood condition caused by complement-mediated hemolysis. In early clinical studies, iptacopan, an oral factor B inhibitor, showed promise in treating PNH. This systematic review aimed to compile information on the effectiveness and safety of iptacopan for PNH.A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The Medline, Embase, PubMed, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies that evaluated iptacopan for PNH. The primary efficacy outcomes were hemoglobin and lactate dehydrogenase (LDH) changes. A fixed-effects model was used for the meta-analysis. Six studies (three prospective cohorts, two RCTs, and one non-randomized trial) were included, comprising 197 patients. Iptacopan therapy significantly increased hemoglobin levels (mean differences (MD) = 12.98 g/L; 95% CI: 11.82-14.13; p < 0.0001) and decreased LDH (MD = -83.55 IU/L; 95% CI: -83.77 to -83.34; p < 0.0001). Subgroup analyses revealed more significant hemoglobin increases in European vs. Asian populations, studies with baseline Hb > 10 g/dL vs. < 10 g/dL, and studies lasting > 24 weeks vs. ≤ 24 weeks. LDH decreases were more pronounced in studies with baseline LDH > 500 IU/L vs. < 500 IU/L. The incidence of adverse events ranged from 66% to 90%, with the most common being headache, nasopharyngitis, and diarrhea. Serious adverse events occurred in 0-20% of patients across studies. Only one patient withdrew because adverse effects were reported across all studies.Preliminary data support iptacopan's effectiveness in improving hemoglobin levels and lowering hemolysis in PNH, both as a monotherapy and in combination with usual treatment. The safety profile appears to be excellent, with a minimal incidence of major adverse events and treatment discontinuation. Further studies are needed to validate the effectiveness and safety of larger, longer-term trials. Iptacopan is a viable oral therapy option for PNH.

Combination of High-Dose Daptomycin and Ceftriaxone for Cardiac Implantable Electronic Device Infections: A 10-Year Experience

PurposeCardiac implantable electronic device (CIED) infections are increasingly common. Gram-positive bacteria such as coagulase negative staphylococci and Staphylococcus aureus are the most commonly involved pathogens. The aim of this study was to describe the characteristics and outcome of patients with CIED infections who underwent device removal and were empirically treated with high dose (8–12 mg/kg daily) daptomycin (DAP) in combination with ceftriaxone (CRO). MethodsRetrospective, single center study including patients admitted at IRCCS San Raffaele Hospital (Milan, Italy), from June 2011 to June 2021, who underwent device removal for CIED infection and were empirically treated with DAP/CRO. FindingsOverall, 147 patients were included in this study. Median duration of therapy was 16 days (IQR 14–26). Empirical treatment with DAP/CRO was confirmed as definitive treatment in 140 patients (95.2%). In 7 (4.8%) patients DAP/CRO were discontinued according to the definite microbiological isolates: Corynebacterium spp. (4), Pseudomonas aeruginosa (2), Enterobacter cloacae (1). Ten patients (6.8%) underwent treatment simplification to narrow-spectrum antibiotics. One patient (0.6%) interrupted DAP-CRO due to pancytopenia.6-month follow-up was available for 123/147 patients (83.7%): 9 patients recurred with a CIED infection (7.3%), and 9 died (7.3%). ImplicationsIn our 10-year experience, high-dose DAP in combination with CRO represented a good option for empirical therapy of CIED infections. DAP-CRO combination was safe and effective, showing no significant drug-related adverse events and low rates of 6-month recurrence and mortality.

Strategies, Challenges, and Prospects of Nanoparticles in Gynecological Malignancies.

Gynecologic cancers are a significant health issue for women globally. Early detection and successful treatment of these tumors are crucial for the survival of female patients. Conventional therapies are often ineffective and harsh, particularly in advanced stages, necessitating the exploration of new therapy options. Nanotechnology offers a novel approach to biomedicine. A novel biosensor utilizing bionanotechnology can be employed for early tumor identification and therapy due to the distinctive physical and chemical characteristics of nanoparticles. Nanoparticles have been rapidly applied in the field of gynecologic malignancies, leading to significant advancements in recent years. This study highlights the significance of nanoparticles in treating gynecological cancers. It focuses on using nanoparticles for precise diagnosis and continuous monitoring of the disease, innovative imaging, and analytic methods, as well as multifunctional drug delivery systems and targeted therapies. This review examines several nanocarrier systems, such as dendrimers, liposomes, nanocapsules, and nanomicelles, for gynecological malignancies. The review also examines the enhanced therapeutic potential and targeted delivery of ligand-functionalized nanoformulations for gynecological cancers compared to nonfunctionalized anoformulations. In conclusion, the text also discusses the constraints and future exploration prospects of nanoparticles in chemotherapeutics. Nanotechnology will offer precise methods for diagnosing and treating gynecological cancers.

Perspectives of Social Anxiety in Relation to Academic Performance among Undergraduate Students in Zanzibar

This study dealt with perspectives of social anxiety in relation to academic performance among undergraduate students in Zanzibar. The study employed the descriptive design. The study purposely selected three out of six universities. The total population was 5,600 students from which the researchers selected a sample size of 230 subjects. The study used a questionnaire and an interview schedule as data collection tools. Data analysis took place through descriptive statistics and content analysis approach. Based on the findings, the study concludes that social anxiety is prevalent among university students in Zanzibar. Most of the students experienced moderate level of social anxiety with basic symptoms like reduced engagement in class activities and fear of public speaking. Only a few exhibited mild to severe symptoms of social anxiety. The study recommends that universities in Zanzibar should provide students’ access to mental health services, providing counseling and therapy options to students with social anxiety. The universities should also provide workshops on stress management for students to managee their social anxiety symptoms effectively. They should also develop initiatives that promote inclusive and supportive classroom settings in terms of peer mentoring and group study sessions to reduce the participation and public speaking pressure.

Exploring the protective potential of NRF2 overexpressed neural extracellular vesicles against cisplatin-induced neurotoxicity via NRF2/ARE pathway

Neurotoxicity is characterized by the accumulation of harmful chemicals such as heavy metals and drugs in neural tissue, resulting in subsequent neuronal death. Among chemicals platinum-based cancer drugs are frequently used due to their antineoplastic effects, but this drug is also known to cause a wide range of toxicities, such as neurotoxicity. The nuclear-factor-erythroid 2-related factor-2 (NRF2) is crucial in combating oxidative stress and maintaining cellular homeostasis. This study thoroughly explores the protective effects of extracellular vesicles derived from NRF2 gene overexpressed neural progenitor cells (NEVs) on cisplatin-induced neurotoxicity. Therefore, extracellular vesicles derived from neural progenitor cells were isolated and characterized. The Cisplatin neurotoxicity dose was 75 µM in mature, post-mitotic neurons. 1.25 µM of tert-butyl hydroquinone that induces NRF2/ARE pathway was used as the positive control. The effects of extracellular vesicles (EVs) were investigated using functional and molecular assays such as PCR and protein-based assays. Here, we observed that NEVs dose-dependently protected post-mitotic neuron cells in response to cisplatin. The study also examined whether the effect was EV-induced by limiting EV biogenesis. The molecular basis of preventive treatment was established. When pre-administered, 1×108 particles/ml of NEVs maintained antioxidant and detoxifying gene and protein expression levels similar to control cell levels. Furthermore, NEVs reduced both cellular and mitochondrial ROS levels and preserved mitochondrial membrane potential. In addition, Catalase and SOD levels were found higher in NEV-treated cells compared to cisplatin control. The findings in NRF2-based protection of cisplatin-induced neurotoxicity may provide further evidence for the relationship between EVs and inhibition of neuronal stress through the NRF2/ARE pathway, increasing the understanding of neuroprotective responses and the development of gene-engineered EV therapy options for peripheral neuropathy or other neurodegenerative diseases. This is the first study in the literature to investigate the neutralizing potency of NRF2 overexpressed neural EVs against cisplatin-induced neurotoxicity.

Recipients of public assistance with advanced chronic kidney disease: insights into receiving a presentation of kidney replacement therapy options and polypharmacy from Japanese investigators with innovative network about kidney disease study.

The characteristics of patients with advanced chronic kidney disease (CKD) who are recipients of public assistance in Japan, and the adequacy of their medical care have not been reported previously. The records of patients with CKD stage G5 who visited nine facilities in Japan from April to June 2013 were retrospectively reviewed to compare the characteristics and care of recipients of public assistance with those of non-recipients. Receiving a presentation of kidney replacement therapy (KRT) options and polypharmacy were used as indicators of suboptimal medical care. Of the 592 patients included in this analysis (mean age, 69.6years; male, 59.3%), 56 (9.5%) were recipients of public assistance and 536 (90.5%) were non-recipients of public assistance. The prevalence of diabetes mellitus, unmarried status, and living alone were higher in recipients of public assistance. In multivariable logistic regression analysis, compared with non-recipients of public assistance, recipients of public assistance were less likely to receive a presentation of KRT options (adjusted odds ratio [aOR], 0.31; 95% confidence interval [CI], 0.17-0.56), and were more likely to receive ≥ 10 (aOR, 1.92; 95% CI, 1.05-3.51), and ≥ 15 (aOR, 2.78; 95% CI, 1.23-6.26) types of medication. Patients with advanced CKD receiving public assistance were less likely to receive a presentation of KRT options and more likely to receive ≥ 10 and ≥ 15 types of medication, suggesting that recipients of public assistance are more likely to receive suboptimal medical care.

Extended Intraocular Drug-Delivery Platforms for the Treatment of Retinal and Choroidal Diseases.

Purpose: To review sustained-release intraocular platforms used to treat diseases of the retina and choroid. Methods: A literature review of the current applications of biomaterials for sustained-release therapy in retinal and choroidal diseases was performed. Results: Retinal and choroidal diseases, such as neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), diabetic macular edema (DME), and uveitis, are commonly treated using intravitreal (IVT) therapies that require frequent IVT injections. Multiple sustained-release options for IVT therapy have been approved by the US Food and Drug Administration for the treatment of inflammatory eye diseases, including noninfectious uveitis, infectious diseases, and exudative retinal diseases (eg, retinal venous occlusive disease and DME) using drugs such as fluocinolone acetonide, ganciclovir, and dexamethasone. The platforms for these drugs are biodegradable or nonbiodegradable. They use biomaterials such as polymers and hydrogels and are typically implanted surgically or injected into the vitreous, where they release the drug gradually over months or years. Building on these technologies, novel platforms are being studied that are intended to treat conditions including nAMD, DR, DME, and uveitis. These platforms are being tested for their safety, efficacy, and ability to reduce the injection and visit burden. Conclusions: Multiple sustained-release ocular drug-delivery platforms are currently commercially available, and many new sustained-release IVT platforms are being investigated. The hope is that meaningfully reducing the injection burden by extending intervals between treatments while maintaining optimal efficacy will improve long-term outcomes.

The safety and efficacy of neoadjuvant PD-1 inhibitor plus chemotherapy for patients with locally advanced gastric cancer: A systematic review and meta-analysis.

The extensive utilization of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) has achieved significant advancements in the treatment of diverse solid tumors. The present meta-analysis aims to evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) plus PD-1 inhibitor for patients with locally advanced gastric cancer (LAGC). An electronic search of PubMed, EmBase, and the Cochrane Library was performed to identify the clinical trials of NCT + PD-1 inhibitor vs. NCT in patients with LAGC. The retrieval period extended from the establishment of the corresponding database until April 2024, and meta-analysis was conducted using Stata (version 15) software. Subsequently, direct comparative analysis was used to compare pooled results of neoadjuvant immunochemotherapy (NICT) with NCT. After screening, 6 phase II/III randomized controlled trials (RCTs) and 9 retrospective studies with 2,953 patients were included. In meta-analysis, NICT group demonstrated a significantly higher rate of pathological complete response (pCR) (P<0.001) and R0 resection (P=0.001), and a lower 2-year recurrence rate (P=0.001) compared to the NCT group. The NICT group, however, exhibited a higher incidence of severe treatment-related adverse events (TRAEs) (P=0.044). Additionally, the NICT and NCT groups exhibited no statistical differences in terms of the number of harvested lymph nodes, the occurrence of total TRAEs and postoperative complications, as well as the duration of postoperative hospitalization. The combination of PD-1 inhibitor + NCT in LAGC patients enhances the likelihood of achieving radical surgery and improves prognosis, albeit to some extent increasing the risk of severe TRAEs. NICT is anticipated to emerge as the preferred neoadjuvant therapy option for patients diagnosed with LAGC.

Atrial Fibrillation in Heart Failure: Strategies for Restoring Sinus Rhythm

Atrial fibrillation (AF) and heart failure (HF) are epidemics that deserve greater attention in the current era. With improved medical therapies and robust revascularization strategies for acute coronary syndromes, there has been a substantial increase in the population of people living with stable coronary artery disease, which in turn contributes to the AF and HF burden. AF and HF are unique disease processes, in that each can precipitate the other, and in those with co-existing AF and HF, the burden of morbidity and mortality is amplified. While there has been remarkable progress in the sphere of pharmacological therapy for HF (particularly HF with reduced ejection fraction), medical therapy options for rate and rhythm control for AF have been largely unchanged for several decades. Instead, advances in catheter ablation (CA) technology and strategies for AF ablation have culminated in a robust evidence base, showing improved survival, quality of life, and restoration of ventricular function. The purpose of this clinical review article is to summarize the pathophysiological link between AF and HF and to emphasize the role of CA in the management of such patients.

Cytologic Findings and Ancillary Tests Results of Sclerosing Pneumocytoma: Our Institutional Experience.

Sclerosing pneumocytoma (SP) is a rare benign tumor and a potential diagnostic pitfall. Our aim was to review the cytologic features of our surgically diagnosed SP cases including the clinical, immunohistochemical and available molecular findings. A computerized search from 2013 to 2020 for surgical cases with corresponding cytology specimens diagnosed as SP was performed. The clinical data, cytology, and surgical specimens were collated for analysis. Six cytology specimens were collected. All were female (mean age = 35). Three have incidental lung nodules and three with cough. Cytologic findings showed variable architectural pattern (papillary, solid, singly scattered, acinar/rosette-like) and cellular heterogeneity (surface, stromal, epithelioid, plasmacytoid cells). Atypia was identified in 4/6 cases. The original cytology diagnoses were negative = 1, SP = 2 and adenocarcinoma = 3. The latter diagnoses were amended to SP after review of the surgical specimens. The three false positive cases on review have cytologic features mimicking adenocarcinoma. Immunohistochemical stains showed tumor cells (surface and stromal) were positive for TTF-1, and EMA with only the surface cells positive for pancytokeratin and Napsin A. Though two cases sent for molecular testing were negative for AKT1 or CTNNB1 exon 3 mutation, our panel did not evaluate AKT1 exon 4. SP is a diagnostic pitfall with 50% initially misdiagnosed as adenocarcinoma. Integrating the clinical/radiologic findings, cytologic features, and performance of immunohistochemistry on cell block are helpful in avoiding misdiagnosis. Molecular testing for recurrent mutations, if present, could be helpful for diagnosis and possible therapy options. However, routinely used molecular testing may not always capture relevant molecular markers for SP.

Post-traumatic cognitive disorders: the cholinergic therapy options

Traumatic brain injury (TBI) is one of the most common causes of neurological disability in young and middle-aged people. Cognitive impairment is the most persistent and universal brain injury syndrome in cases of TBI and, moreover, the best indicator of TBI severity to predict its outcome. Cognitive impairment can persist persistently even after mild TBI, which accounts for 70–90 % of the total number of trauma patients. This may be due to the fact that in cases of mild TBI, the most fragile functions of integrative structures of the frontal and temporal lobes are slowly and not always completely recovered and the dominant clinical manifestation become complex neuropsychological disorders. Individuals with repeated mild TBI are characterized by development of chronic post-traumatic encephalopathy, that is a kind of neurodegenerative disease manifested by slowly increasing cognitive impairment, parkinsonism and a number of other neurological syndromes. Early detection and adequate correction of the cognitive impairments may improve the outcome of injury of diverging severity. Due to the fact that the pathogenesis of TBI is based on disorder of cholinergic system, the patients have predominance of regulatory disorders in the neuropsychological profile, as well as a combination of cognitive and affective disorders. Administration of acetylcholine precursors leads to rapid increase of free choline levels in plasma that penetrates the blood-brain barrier well and enhances cholinergic activity by increasing acetylcholine synthesis and release. The article considers the possibilities of using acetylcholine precursors in connection with their potential to block the progressive impairment of cognitive functions induced by trauma as well as to reduce severity of behavioral and affective disorders.

Comparing the activity of broad-spectrum beta-lactams in combination with aminoglycosides against VIM-producing Enterobacteriaceae.

Metallo-beta-lactamase (MBL)-producing carbapenem-resistant Enterobacteriaceae (CRE) infections continue to pose a serious threat to healthcare. Due to their unique active site, MBLs evade the activity of many novel beta-lactam/beta-lactamase inhibitor combinations, which have been specifically targeted toward those carbapenemases with serine active sites. Furthermore, resistance to most, if not all, other clinically relevant antimicrobial classes leaves few reliable therapeutic options. Combination therapy has thus played a vital role in the treatment of MBL-producing CRE infections. In this study, we utilized the static time-kill assay to investigate clinically relevant concentrations of cefepime, piperacillin-tazobactam, and meropenem alone and in combination with either amikacin or the novel plazomicin to determine if combinations of routinely used beta-lactam therapy with an aminoglycoside would achieve bactericidal activity against eight clinically isolated Verona integron-encoded MBL (VIM)-producing CRE. Furthermore, we compared this activity to the combination of aztreonam/avibactam, which has shown potent activity against MBL-producing CRE. Both aztreonam/avibactam and meropenem with either aminoglycoside were rapidly bactericidal within 4 hours and remained bactericidal through 24 hours against all isolates with few exceptions. Combinations including cefepime and piperacillin-tazobactam were also rapidly bactericidal, but activity after 24 hours was inconsistent depending upon the partner aminoglycoside and isolate. Further investigation is warranted to elucidate optimal antibiotic exposures against MBL-producing CRE, including novel agents in the pipeline.IMPORTANCECarbapenem-resistant Enterobacterales (CRE) are one of the most pressing antimicrobial-resistant threats at present. In addition to exhibiting resistance to many, if not all, commonly used antimicrobial agents, CRE achieves these resistant phenotypes through a variety of mechanisms, each of which can uniquely affect available treatment options. The present study is an in vitro investigation of several Verona integron-encoded metallo-beta-lactamase (VIM)-producing CRE isolated from patients at our academic medical center. Because metallo-beta-lactamases (MBLs) are inherently resistant to many of the novel treatments designed to treat CRE due to their different active site composition, we tested several antimicrobial combinations containing routinely utilized broad-spectrum beta-lactams and aminoglycosides. Our results further our understanding of combination therapy options against VIM-producing CRE, including with non-carbapenem-beta-lactams cefepime and piperacillin. By optimizing combinations of existing antimicrobial agents, we hope to expand the available armamentarium against these resistant pathogens.

Provision of transplant education for patients starting dialysis: Disparities persist

BackgroundAll patients starting dialysis should be informed of kidney transplant as a renal replacement therapy option. Prior research has shown disparities in provision of this information. In this study, we aimed to identify patient sociodemographic and dialysis facility characteristics associated with not receiving transplant information at the time of dialysis initiation. We additionally sought to determine the association of receiving transplant information with waitlist and transplant outcomes. MethodsWe retrospectively analyzed CMS-2728 forms filed from 2007 to 2019. The primary outcome was report of provision of information about transplant on the Centers for Medicare and Medicaid Services Form CMS-2728. For patients not informed at the time of dialysis, we collected the reported reason for not being informed (medically unfit, declined information, unsuitable due to age, psychologically unfit, not assessed, or other). Cox proportional-hazards model estimates were used to study determinants of addition to the waitlist and transplant (secondary outcomes). ResultsFifteen percent of patients did not receive information about transplant (N = 133,414). Non-informed patients were more likely to be older, female, white, and on Medicare. Patients informed about transplant had a shorter time between end-stage renal disease onset and addition to the waitlist; they also spent a shorter time on the waitlist before receiving a transplant. Patients at chain dialysis facilities were more likely to receive information, but this did not translate into higher waitlist or transplant rates. Patients at independent facilities acquired by chains were more likely to be informed but less likely to be added to the waitlist post acquisition. ConclusionsDisparities continue to persist in providing information about transplant at initiation of dialysis. Patients who are not informed have reduced access to the transplant waitlist and transplant. Maximizing the number of patients informed could increase the number of patients referred to transplant centers, and ultimately transplanted. However, policy actions should account for differences in protocols stemming from facility ownership.

Pulmonary Adenocarcinoma with Enteric Differentiation without TTF-1 Expression Is a Very Rare Subtype with Limited Treatment Options and Poor Prognosis

Plain Language SummaryPulmonary adenocarcinoma with enteric differentiation (PAED) without expression of thyroid transcription factor-1 (TTF-1) is an extremely rare and hard-to-treat variant of lung cancer. We collected clinicopathological data of 121 Caucasian patients with pulmonary adenocarcinoma without TTF-1 expression, their systemic therapy options, and the efficacy of their systemic treatment including 79 cases without a PAED and 42 cases with a PAED, compared these subgroups, and investigated patients’ response to chemotherapy and immunotherapy as first-line treatment. A comparison of clinicopathological data of TTF-1-negative PAED and non-PAED patients revealed a significantly lower frequency of high programmed death receptor ligand 1 (PD-L1) expression in PAED resulting in the lack of single-agent immunotherapy (p = 0.032) in this subgroup. Frequencies of an activating Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation were high in both groups (46.7% and 50.0%), but a G12C gene mutation was seldomly noted (in 6.7% and 18.5% of patients with evaluable data). Median overall survival (OS) was poor in both groups (10 and 12 months). The majority of PAED patients received platinum-based and taxane-containing chemotherapy or chemo-/immunotherapy with an objective response rate of 31.6% and a disease control rate of 57.9%. Median progression-free survival (PFS) and OS of PAED patients with systemic therapy were very poor (3.9 months and 5.9 months). Caucasian patients with a TTF-1-negative PAED have a poor prognosis with reduced response rates to standard first-line systemic therapy and short survival times (PFS and OS).

The effect of tocilizumab administration on inflammatory markers in COVID-19 patients

BackgroundThe COVID-19 outbreak was declared a worldwide emergency as a result of its rapid spread. The number of people infected with COVID-19 is increasing rapidly around the world, and pneumonia can develop in COVID-19 cases. The monoclonal antibody tocilizumab blocks the interleukin-6 receptor, which in turn reduces inflammation.Aimof the workThe study aims to determine how tocilizumab affects inflammatory markers, laboratory indices, and oxygen therapy.Subjects and methodsThis retrospective observational study aimed to assess the effect of tocilizumab on inflammatory markers, laboratory parameters, and short-term outcomes in COVID-19 cases. Data was collected from 55 patients with COVID-19 who tested positive for SARS-CoV-2 using PCR. These patients were admitted to Ain Shams University Specialized Hospital—Obour between June 1, 2021, and May 31, 2022.ResultsAfter tocilizumab administration, C-reactive protein levels decreased significantly, but there was no statistically significant change in hemoglobin, serum ferritin, or D-dimer levels. Following tocilizumab administration, the leukocyte counts, and platelet count increased significantly. There was a significant correlation between the presence of comorbidities in the studied patients (e.g., heart failure, post-renal transplantation, and hepatitis C virus) and the risk of mortality. The study's final result showed a significant decrease in platelet count in dead patients compared to discharged patients after receiving tocilizumab. Regarding oxygen therapy following tocilizumab administration, the use of face masks and non-rebreather facemasks was high in dead patients, while nasal prong usage was high in discharged patients. After receiving tocilizumab, there was an increase in the mean liters of oxygen required in dead patients compared to discharged patients.ConclusionAfter administration of tocilizumab in COVID-19 hospitalized patients who have progressing disease, there was highly and significantly decrease in CRP level with no statistically significant alteration in the levels of hemoglobin, serum ferritin, and D-dimer and an increase in TLC and platelets was observed. Following tocilizumab administration, there was a decrease in oxygen demands, an improvement in oxygen therapy and oxygen saturation. Tocilizumab is a recommended therapy option.

Non-binary patients in ART: new challenges and considerations.

To discuss the increasing visibility of non-binary individuals and inclusive policies and practices in assisted reproductive technologies (ART). Comparison between traditional ART approach designed for binary genders and propose approach in non-binary individuals. Traditional ART services, designed for binary genders, must adapt to address the unique fertility needs of non-binary patients. This includes using gender-neutral language, providing comprehensive fertility assessments, and offering hormone therapy and fertility preservation options. Children of non-binary parents benefit from open communication about gender diversity, enhancing psychological well-being. Positive societal attitudes and inclusive environments in schools are crucial for preventing discrimination and promoting mental health. A systemic approach is required to make ART inclusive. This involves training staff, adjusting facilities, updating documentation, and advocating for supportive legislation. Addressing the reproductive needs of non-binary individuals ensures equitable access to care and supports their family-building goals. Ensuring the well-being of children in non-binary families requires psychological support, inclusive healthcare, legal recognition, social support, and comprehensive education.

Triple Combinations of AAV9-Vectors Encoding Anti-HIV bNAbs Provide Long-Term In Vivo Expression of Human IgG Effectively Neutralizing Pseudoviruses from HIV-1 Global Panel.

Anti-human immunodeficiency virus (HIV) broadly neutralizing antibodies (bNAbs) offer a promising approach for the treatment of HIV-1. The current paradigm for antibody therapy involves passive antibody transfer, requiring regular delivery of bNAbs in treating chronic diseases such as HIV-1. An alternative strategy is to use AAV-mediated gene transfer to enable in vivo production of desirable anti-HIV-1 antibodies. In this study, we investigated two sets of triple combinations of AAV9-vectors encoding different bNAbs: N6, 10E8, 10-1074 (CombiMab1), and VRC07-523, PGDM1400, 10-1074 (CombiMab2). We used CBAxC57Bl and C57BL/6 mouse models to characterize rAAV-induced antibody expression and to evaluate the neutralization capacity of mouse sera against a global panel of HIV-1 viral strains. rAAV9-mediated IgG expression varied between bNAb clones and mouse strains, with C57BL/6 mice exhibiting higher bNAb titers following rAAV delivery. Although CombiMab2 treatment elicited a higher IgG titer than CombiMab1, both combinations resulted in neutralization of all the viral strains from the global HIV-1 panel. Our data highlight the potential of AAV vectors as a long-term option for HIV-1 therapy.

Lateral pelvic lymph nodes dissection of rectal neuroendocrine neoplasms: A prospective case-series and literature review

BackgroundRectal neuroendocrine neoplasms are relatively rare. Patients with rectal neuroendocrine neoplasms undergoing radical surgery have a higher rate of lymph node metastases. Robust evidence on the status of lateral pelvic lymph node metastases and the role of lateral pelvic lymph node dissection in those patients is lacking. This case-series study aimed to explore and address these issues. MethodsThis single-center, prospective case series consecutively enrolled patients with biopsy-proven rectal neuroendocrine neoplasms in a tertiary referral hospital between June 2022 and January 2024. All eligible patients underwent laparoscopic total mesorectal excision surgery and bilateral lateral pelvic lymph node dissection under general anesthesia. The clinicopathologic features, surgical outcomes, and postoperative complications were presented. The last follow-up was conducted in March 2024. ResultsA total of 11 patients with rectal neuroendocrine neoplasms—3 female and 8 male—were enrolled. The average age was 60.0 years (range, 53.5–65.5 years), and the median tumor size was 2.0 cm (range, 1.6–2.5 cm). Tumors invaded the muscularis propria in 7 patients. There were 3 cases of neuroendocrine tumor G1, 6 cases of neuroendocrine tumor G2, and 2 cases of neuroendocrine carcinoma. Among these patients, 11 (100.0%) had lymph node metastases, and 6 (54.5%) had lateral pelvic lymph node metastases. In addition, in 2 patients, only lateral pelvic lymph node metastases were observed, without involvement of the mesenteric lymph nodes. Five patients had tumors located on the left wall of the rectum, and only left-sided lateral pelvic lymph node metastases were observed. The other patient had both sides of lateral pelvic lymph node metastases due to circumferential growth of the tumor around the rectum. Anal preservation was achieved in all patients. The median operating time was 235.0 minutes (range, 210.5–335.5 minutes), and the median estimated blood loss was 50.0 mL (range, 45.0–75.0 mL). Two patients experienced postoperative dysuria and recovered spontaneously within 2–4 months after surgery. ConclusionOn the basis of a prospective case series, we demonstrate, for the first time, the lateral pelvic lymph node metastasis status in patients with rectal neuroendocrine neoplasms requiring radical total mesorectal excision surgery. Simultaneous bilateral lateral pelvic lymph node dissection may be a feasible and beneficial procedure for preventing local recurrence in these patients due to the lack of definitive neoadjuvant or adjuvant therapy options.

Gepirone: A New Extended-Release Oral Selective Serotonin Receptor Agonist for Major Depressive Disorder.

Objective: To evaluate the safety, efficacy, and tolerability of gepirone (Exxua) in the treatment of adult patients with major depressive disorder. Data Sources: A literature search was performed through PubMed, Embase, and PsycINFO using the following terms: Exxua, gepirone, depression, major depressive disorder, anxiety, and anxiety disorders. Study Selection and Data Extraction: Articles that were selected included English-language dominant studies, or studies that could be translated into English by the authors, with terms associated with the safety, efficacy, and/or tolerability of gepirone. Data Synthesis: Gepirone exhibits its antidepressant activity through agonism of 5HT1A serotonin receptors. Phase 3 clinical trials showed that gepirone at a dose of 20 to 80 mg was proven to be effective in the treatment of major depressive disorder in adult patients. Common adverse effects reported in clinical trials included dizziness, nausea, headache, fatigue, and insomnia. Conclusion: This review evaluates the pharmacokinetic, pharmacologic, efficacy, and safety profile of gepirone and includes a discussion on its place in therapy for the treatment of major depressive disorder. Most clinical guidelines recommend second-generation antidepressants consisting of selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors as first-line therapy options. Gepirone is expected to receive greater clinical relevance and recommendations when compared to other azapirone medications (buspirone) within practice guidelines. Gepirone could be considered as either an alternative option for patients failing first-line therapies or for initial use to avoid unwanted side effects of other therapy options in the treatment of adult patients with major depressive disorder.