Clinical Therapeutic Outcomes Research Articles

Impact of different CEBPA mutations on therapeutic outcome in acute myeloid leukemia.

Biallelic mutations of the CEBPA gene (CEBPAbi) are generally associated with favorable prognosis in patients with acute myeloid leukemia (AML). Monoallelic mutations of the CEBPA gene in carboxy-terminal DNA-binding region (CEBPAsmbZIP) and amino-terminal transactivation domains (CEBPAsmTAD) indicate distinct clinical characteristics and therapeutic outcomes. However, further investigation is required to fully understand these differences. In this retrospective study, we enrolled 77 AML patients with CEBPA mutations, including 53 with CEBPAbi, 12 with CEBPAsmbZIP and 12 with CEBPAsmTAD. The clinical characteristics of the three CEBPAmut groups presented significant differences in age, FAB classification, hemoglobin level and platelet count at diagnosis. The CEBPAsmTAD group exhibited shorter 2-year overall survival (OS) and relapse-free survival (RFS) compared to the CEBPAbi group and CEBPAsmbZIP group in AML patients. The most common co-mutations observed in CEBPAmut AML patients were TET2 and GATA2, which had no effect on prognosis. 2-year RFS of 27 CEBPAmut AML patients who underwent allo-HSCT was better than those who did not. MRD3 positive was identified as an influencing factor for 2-year OS and RFS. Allo-HSCT was found to improve the prognosis of CEPBAmut AML patients with positive MRD3 and adverse co-mutations.

Efficacy and safety of arterial FOLFOX chemotherapy plus anti-PD-(L)1 immunotherapy as first-line treatment for unresectable intrahepatic cholangiocarcinoma: A propensity score matched analysis.

e16189 Background: This study aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus anti-programmed death (ligand)-1 [PD-(L)1] immunotherapy compared to systemic chemotherapy (SCT) plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with unresectable intrahepatic cholangiocarcinoma (uICC). Methods: In this retrospective study, unresectable treatment-naive ICC patients who were treated with HAIC plus anti-PD-(L)1 immunotherapy [HAIC+αPD-(L)1] or SCT plus anti-PD-(L)1 immunotherapy [SCT+αPD-(L)1] were included. The clinical characteristics, therapeutic outcomes and adverse events (AEs) of patients between the two groups were compared. The propensity score matching (PSM) was performed to minimize biases between groups. Results: From January 2019 to January 2023, a total of 182 patients were enrolled, including 147 patients in HAIC+αPD-(L)1 group and 35 patients in SCT+αPD-(L)1 group. After PSM, 61 and 26 patients were included in the HAIC+αPD-(L)1 and SCT+αPD-(L)1 groups, respectively. The HAIC+αPD-(L)1 group showed longer median overall survival (OS) and progression free survival (PFS) than the SCT+αPD-(L)1 group (OS: 14.5 vs 10.5 months, P = 0.019; PFS: 6.4 vs 10.1 months, P = 0.020). The disease control rate of HAIC+αPD-(L)1 group were higher than those of SCT+αPD-(L)1 group (91.8% vs 69.2%, P = 0.007). The overall incidence of adverse events (AEs) was comparable between the two groups, but the HAIC+αPD-(L)1 group showed a lower incidence of grade 3~4 AEs related to anemia, weight loss and fatigue. Conclusions: HAIC plus anti-PD-(L)1 immunotherapy had acceptable toxic effects and might improve outcomes compared to SCT plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with uICC.

Efficacy and safety of arterial FOLFOX chemotherapy plus anti-PD-(L)1 immunotherapy as first-line treatment for unresectable intrahepatic cholangiocarcinoma: A propensity score matched analysis.

e16189 Background: This study aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus anti-programmed death (ligand)-1 [PD-(L)1] immunotherapy compared to systemic chemotherapy (SCT) plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with unresectable intrahepatic cholangiocarcinoma (uICC). Methods: In this retrospective study, unresectable treatment-naive ICC patients who were treated with HAIC plus anti-PD-(L)1 immunotherapy [HAIC+αPD-(L)1] or SCT plus anti-PD-(L)1 immunotherapy [SCT+αPD-(L)1] were included. The clinical characteristics, therapeutic outcomes and adverse events (AEs) of patients between the two groups were compared. The propensity score matching (PSM) was performed to minimize biases between groups. Results: From January 2019 to January 2023, a total of 182 patients were enrolled, including 147 patients in HAIC+αPD-(L)1 group and 35 patients in SCT+αPD-(L)1 group. After PSM, 61 and 26 patients were included in the HAIC+αPD-(L)1 and SCT+αPD-(L)1 groups, respectively. The HAIC+αPD-(L)1 group showed longer median overall survival (OS) and progression free survival (PFS) than the SCT+αPD-(L)1 group (OS: 14.5 vs 10.5 months, P = 0.019; PFS: 6.4 vs 10.1 months, P = 0.020). The disease control rate of HAIC+αPD-(L)1 group were higher than those of SCT+αPD-(L)1 group (91.8% vs 69.2%, P = 0.007). The overall incidence of adverse events (AEs) was comparable between the two groups, but the HAIC+αPD-(L)1 group showed a lower incidence of grade 3~4 AEs related to anemia, weight loss and fatigue. Conclusions: HAIC plus anti-PD-(L)1 immunotherapy had acceptable toxic effects and might improve outcomes compared to SCT plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with uICC.

The nuclear export protein exportin-1 in solid malignant tumours: From biology to clinical trials.

Exportin-1 (XPO1), a crucial protein regulating nuclear-cytoplasmic transport, is frequently overexpressed in various cancers, driving tumor progression and drug resistance. This makes XPO1 an attractive therapeutic target. Over the past few decades, the number of available nuclear export-selective inhibitors has been increasing. Only KPT-330 (selinexor) has been successfully used for treating haematological malignancies, and KPT-8602 (eltanexor) has been used for treating haematologic tumours in clinical trials. However, the use of nuclear export-selective inhibitors for the inhibition of XPO1 expression has yet to be thoroughly investigated in clinical studies and therapeutic outcomes for solid tumours. We collected numerous literatures to explain the efficacy of XPO1 Inhibitors in preclinical and clinical studies of a wide range of solid tumours. In this review, we focus on the nuclear export function of XPO1 and results from clinical trials of its inhibitors in solid malignant tumours. We summarized the mechanism of action and therapeutic potential of XPO1 inhibitors, as well as adverse effects and response biomarkers. XPO1 inhibition has emerged as a promising therapeutic strategy in the fight against cancer, offering a novel approach to targeting tumorigenic processes and overcoming drug resistance. SINE compounds have demonstrated efficacy in a wide range of solid tumours, and ongoing research is focused on optimizing their use, identifying response biomarkers, and developing effective combination therapies. Exportin-1 (XPO1) plays a critical role in mediating nucleocytoplasmic transport and cell cycle. XPO1 dysfunction promotes tumourigenesis and drug resistance within solid tumours. The therapeutic potential and ongoing researches on XPO1 inhibitors in the treatment of solid tumours. Additional researches are essential to address safety concerns and identify biomarkers for predicting patient response to XPO1 inhibitors.

Laponite/lactoferrin hydrogel loaded with eugenol for methicillin-resistant Staphylococcus aureus-infected chronic skin wound healing

Severe bacterial infections can give rise to protracted wound healing processes, thereby posing a significant risk to a patient's well-being. Consequently, the development of a versatile hydrogel dressing possessing robust bioactivity becomes imperative, as it holds the potential to expedite wound healing and yield enhanced clinical therapeutic outcomes. In this context, the present study involves the formulation of an injectable multifunctional hydrogel utilizing laponite (LAP) and lactoferrin (LF) as foundational components and loaded with eugenol (EG). This hydrogel is fabricated employing a straightforward one-pot mixing approach that leverages the principle of electrostatic interaction. The resulting LAP/LF/EG2% composite hydrogel can be conveniently injected to address irregular wound geometries effectively. Once administered, the hydrogel continually releases lactoferrin and eugenol, mitigating unwarranted oxidative stress and eradicating bacterial infections. This orchestrated action culminates in the acceleration of wound healing specifically in the context of MRSA-infected wounds. Importantly, the LAP/LF/EG2% hydrogel exhibits commendable qualities including exceptional injectability, potent antioxidant attributes, and proficient hemostatic functionality. Furthermore, the hydrogel composition notably encourages cellular migration while maintaining favorable cytocompatibility. Additionally, the hydrogel manifests noteworthy bactericidal efficacy against the formidable multidrug-resistant MRSA bacterium. Most significantly, this hydrogel formulation distinctly expedites the healing of MRSA-infected wounds by promptly inducing hemostasis, curbing bacterial proliferation, and fostering angiogenesis, collagen deposition, and re-epithelialization processes. As such, the innovative hydrogel material introduced in this investigation emerges as a promising dressing for the facilitation of bacterial-infected wound healing and consequent tissue regeneration.

Clinical Management practice and Therapeutic Outcomes of Chronic Liver Disease patients in the Conflicted area of North Ethiopia

Background: In the 21st century, low- and middle income, war prone and drought-prone areas in developing nations have seen a fast rise in the prevalence of chronic liver disease (CLD). An estimated 240 million people worldwide are infected with HIV, and 780,000 deaths are attributed to it each year, according to the World Health Organization (WHO). Objective: We want to assess the efficacy of in-hospital care for CLD patients by verifying and evaluating current management practices. Method: A retrospective descriptive study of patients with chronic liver disease who were followed up on at Debre Berhan Hospital between July 2018 and January 2021 was conducted. Results: Out of a total of 209 patients tested, 127 (or 60.74%) were males aged 41.44±12.89 of years. Ascites complications were presented in over 44% of cases. Using the laboratory data, 65 patients (31.10%) and 71 patients (33.97%) were found to have abnormally high AST and ALT values on LFTs testing. AUROC analysis was carried out with a 95% CI for Child-Pugh of 0.61 (0.53-0.75, P=0.14), MELD 0.75 (0.63-0.72, P=0.26), and ALBI 0.53 (0.31-0.54, P=0.29). Conclusion: Based on the predictive data, 87 (41.63%) patients were successfully treated and released, whereas 57(27.27%) were recommended for further care, and 47 died due to co-morbid conditions. Although, the study period coincides with the COVID-19 pandemic, more analysis of the obtained data is necessary.

Clinical manifestations and outcomes of otitis media with effusion in adult patients following Omicron infection in China.

This study investigates the clinical features and therapeutic outcomes of otitis media with effusion (OME) in adults following infection with the Omicron variant of coronavirus disease 2019 (COVID-19), in the context of China ending its "Zero-COVID-19" policy. Conducted as a multicenter, retrospective analysis at two medical institutions in Eastern China from December 2022 to February 2023, the study included patients with confirmed Omicron infection who were diagnosed with OME within two months, adhering to guidelines from the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF). Data on demographics, time from infection to OME manifestation, associated symptoms, and treatment outcomes were collected. Among 68 patients (73 affected ears) with OME post-Omicron infection, common symptoms included cough and nasal obstruction (69.1%). All reported ear fullness, with 86.8% experiencing hearing loss. Tympanic bullae were observed in 72.6% during otoscopy, and most tympanometry results showed a B-type tympanogram (80.0%). An integrated treatment strategy led to an 83.6% cure rate, although 8.2% experienced relapse within 2-3 months. Our findings highlight OME as a prevalent ear complication associated with COVID-19 during the Omicron pandemic, underscoring the necessity for further investigation into its complexities. While the integrated treatment approach proved effective, the 8.2% post-treatment recurrence rate underscores the importance of ongoing monitoring and signals an urgent need for more comprehensive research.

Safety and efficacy of biologic immunosuppressive treatment in juvenile idiopathic arthritis associated with inborn errors of immunity.

This study aims to describe clinical features, therapeutic outcomes, and safety profiles in patients affected by juvenile idiopathic arthritis (JIA) and inborn errors of immunity (IEI) treated with biological Disease-modifying antirheumatic drugs (DMARDs). We enrolled three patients who were followed in the Pediatric Rheumatology Unit at Meyer Children's Hospital in Florence; these patients were affected by JIA, according to ILAR criteria, and IEI, according to the IUIS Phenotypical Classification for Human Inborn Errors of Immunity. Among them, two patients had 22q11.2 deletion syndrome (22q11.2DS) and one patient had X-linked agammaglobulinemia (XLA). Case 1: A 6-year and 2-month-old boy was affected by 22q11.2DS, associated with oligoarticular JIA, at the age of 2 years. He was treated with non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate, along with oral glucocorticoids but with no benefits. Treatment with etanercept allowed him to achieve remission after 10 months. Case 2: A 6-year and 2-month-old girl was affected by 22q11.2DS, associated with oligoarticular JIA, at the age of 3 years and 11 months. She was treated with NSAIDs, joint injections, and methotrexate but without clinical response. Treatment with Adalimumab allowed her to achieve remission after 6 months. Case 3: A 12-year and 2-month-old boy was affected by XLA, associated with polyarticular JIA, at the age of 9 years and 11 months. He was treated with NSAIDs, methotrexate, joint injections, and oral glucocorticoids with no benefits. He failed to respond to anti-TNF-alpha, tocilizumab, and abatacept. Currently, he is undergoing therapy with sirolimus plus abatacept, which allowed him to achieve remission after 4 months. Results suggest that the use of immunosuppressive biological therapies can control disease activity in these patients. No adverse drug-related reactions were observed during the follow-up.

Psoriatic Arthritis Involving TMJ: A Review on Pathogenesis and Consideration on Eventual Gender Differences.

Psoriatic arthritis is defined as chronic inflammatory arthritis associated with psoriasis. The current data regarding gender differences in clinical manifestation and therapeutic outcomes of psoriatic arthritis are limited. Generally, men show a peripheral disease manifestation, while women have an axial distribution of the lesions. If we look at temporomandibular joint (TMJ) involvement, epidemiological data on the involvement of the TMJ are hard to find. Few studies on therapeutic management and the related impact on the quality of life are reported in the literature. Given the morpho-functional peculiarities of the TMJ and the different pain burdens between male and female genders, when manifestation of psoriatic arthritis occurs, clinicians should face it using a multidisciplinary approach for a correct diagnosis and successful treatment. This review aims to examine the diagnostic signs of psoriatic arthritis in the TMJ, the eventual variations of this disease in male and female patients, and the therapeutical strategies. The coordination of different specialties is fundamental to the remission of clinical symptoms and lesion regression.

Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments.

Solid tumors are composed of a highly complex and heterogenic microenvironment, with increasing metabolic status. This environment plays a crucial role in the clinical therapeutic outcome of conventional treatments and innovative antitumor nanomedicines. Scientists have devoted great efforts to conquering the challenges of the tumor microenvironment (TME), in respect of effective drug accumulation and activity at the tumor site. The main focus is to overcome the obstacles of abnormal vasculature, dense stroma, extracellular matrix, hypoxia, and pH gradient acidosis. In this endeavor, nanomedicines that are targeting distinct features of TME have flourished; these aim to increase site specificity and achieve deep tumor penetration. Recently, research efforts have focused on the immune reprograming of TME in order to promote suppression of cancer stem cells and prevention of metastasis. Thereby, several nanomedicine therapeutics which have shown promise in preclinical studies have entered clinical trials or are already in clinical practice. Various novel strategies were employed in preclinical studies and clinical trials. Among them, nanomedicines based on biomaterials show great promise in improving the therapeutic efficacy, reducing side effects, and promoting synergistic activity for TME responsive targeting. In this review, we focused on the targeting mechanisms of nanomedicines in response to the microenvironment of solid tumors. We describe responsive nanomedicines which take advantage of biomaterials' properties to exploit the features of TME or overcome the obstacles posed by TME. The development of such systems has significantly advanced the application of biomaterials in combinational therapies and in immunotherapies for improved anticancer effectiveness.

Clinical characterization and therapeutic outcomes of patients (pts) with colorectal cancer (CRC) harboring somatic BRCA1/2 mutations.

134 Background: Somatic BRCA1/2 mutations in BRCA-associated cancers increase therapeutic sensitivity to platinum-based chemotherapies and PARP inhibitors, but the implications of BRCA mutations in non- BRCA-associated cancers such as CRC is unknown and hypothesized to be shaped by tumor lineage. We thus conducted a retrospective analysis of outcomes with platinum-based chemotherapy and PARP inhibition in pts with CRC, where the estimated prevalence of BRCA1/2 alterations is 3-4%. Methods: Pts with blood or tissue next generation sequencing (NGS) positive for a somatic BRCA1/2 variant and a diagnosis of CRC were identified from a single institution database. The pathogenicity of each mutation was annotated using public genomic databases (e.g. ClinVar). Pt characteristics were compared using Fisher’s exact test. Log-rank test was used for comparison of survival distribution among groups. Results: 8,258 NGS reports with a BRCA1/2 alteration from 1760 cancer pts were identified of which 189 (11%) had a diagnosis of CRC. 54/189 CRC pts (29%) had ≥1 pathogenic BRCA1/2 variant, 19 pts (10%) had ≥1 benign variant, and 134 pts (69%) had 1 ≥ variant of unknown significance (VUS); 26 pts (14%) had more than one BRCA1/2 variant. Pts with ≥1 pathogenic mutation (n=54) were more likely to have an inactivating DNA polymerase epsilon (POLE) mutation versus pts with only benign/VUS BRCA1/2 variants (n=135) (20% vs 6%, p=0.004) while prevalence of microsatellite instability (MSI-H) (19% vs 13%, p=0.37) and Ras/Raf (53% vs 53%, p=1.00) were similar between groups. Median progression free survival (PFS) among 115 CRC pts (unselected for BRCA1/2 pathogenicity) who received an oxaliplatin-based regimen for advanced disease in the 1st line (n=52) was similar to the median PFS among pts who received an irinotecan-based regimen (n=63) (7.0 mths vs 7.0 mths, p=0.48). Median PFS with an oxaliplatin-based regimen in the 1st line among 52 pts with pathogenic BRCA1/2 variants (n=13) was 5.1 mths vs 7.4 mths among pts with benign/VUS BRCA1/2 variants (n=39) (p=0.398). There were no significant differences in median PFS among pts with a pathogenic vs benign/VUS BRCA1/2 variants when the analysis was restricted to pts with BRCA1/2 variants identified in tissue (p=0.76) and to pts without co-occurring driver mutations (Ras/Raf, MSI-H, and/or POLE) (p=0.1). Overall survival in patients with advanced disease was similar between pts with a pathogenic (n=52) vs benign/VUS (n=122) BRCA variants (37.1 mths vs 45.1 mths, p=0.14). 6 pts (4 with pathogenic BRCA1/2 and 3 with VUS) received a PARP inhibitor after a median of 3 lines of treatment and the best response was disease progression in 6 pts (100%). Conclusions: In the context of CRC, somatic BRCA1/2 mutations frequently co-occur with pathogenic POLE mutations, but do not appear to confer therapeutic benefit to platinum-based chemotherapy and PARP inhibitors.

Translation of the working alliance inventory short revised into Italian using a Delphi procedure and a forward-backward translation.

Enhancing treatment adherence, especially for chronic diseases, can be achieved through therapeutic alliance, potentially elevating the quality of care. An instrument to evaluate the therapeutic alliance could be beneficial in routine clinical settings, educational environments, and extensive research efforts at national and European levels. In this study, we translated therapist and patient versions of the Working Alliance Inventory Short Revised (WAI-SR) into Italian. An email-based Delphi method was employed for the English-to-Italian translation, incorporating a forward-backward process. The initial translation team comprised two Italian family physicians proficient in English, a linguist, and a psychiatrist. The forward translation was then reviewed by 18 Italian family physicians through a Delphi process and was subjected to a backward translation by two Italian English teachers. A cultural correspondence was subsequently identified to adjust translations within a national and international framework. All 18 experts fully engaged in the Delphi process, and consensus was achieved by the second Delphi round. A cultural check checked for discrepancies regarding linguistic consistency with other translations and found no difference. This Italian translation of the WAI-SR is expected to support Italian family physicians aiming to enhance their clinical practice and therapeutic outcomes. It could also be a valuable tool for Italian medical students to foster therapeutic relationships and improve their communication skills.

Harnessing tumor-derived exosomes: A promising approach for the expansion of clinical diagnosis, prognosis, and therapeutic outcome of prostate cancer.

Prostate cancer is the second leading cause of men's death worldwide. Although early diagnosis and therapy for localized prostate cancer have improved, the majority of men with metastatic disease die from prostate cancer annually. Therefore, identification of the cellular-molecular mechanisms underlying the progression of prostate cancer is essential for overcoming controlled proliferation, invasion, and metastasis. Exosomes are small extracellular vesicles that mediate most cells' interactions and contain membrane proteins, cytosolic and nuclear proteins, extracellular matrix proteins, lipids, metabolites, and nucleic acids. Exosomes play an essential role in paracrine pathways, potentially influencing Prostate cancer progression through a wide variety of mechanisms. In the present review, we outline and discuss recent progress in our understanding of the role of exosomes in the Prostate cancer microenvironment, like their involvement in prostate cancer occurrence, progression, angiogenesis, epithelial-mesenchymal transition, metastasis, and drug resistance. We also present the latest findings regarding the function of exosomes as biomarkers, direct therapeutic targets in prostate cancer, and the challenges and advantages associated with using exosomes as natural carriers and in exosome-based immunotherapy. These findings are a promising avenue for the expansion of potential clinical approaches.

Effect of levocetirizine hydrochloride on chronic urticaria and serum levels of total IgE and inflammatory factors

Purpose: To investigate the curative effect of levocetirizine hydrochloride tablets on chronic urticaria as well as its mediating effect on serum levels of total IgE and inflammatory factors.
 Methods: Ninety-two (92) patients with chronic urticaria, were randomly divided into control group (CG) and study group (SG). Patients in CG were treated with oral administration of desloratadine citrate tablets while SG patients received oral levocetirizine hydrochloride tablets. A comparative analysis was conducted between the two patient cohorts encompassing clinical therapeutic outcomes, symptom scoring, T lymphoid subset cell levels, serum total IgE concentrations, serum inflammatory factor levels, as well as adverse reactions.
 Results: Total treatment effectiveness was higher in SG (97.83 %) than in CG (82.61 %; p < 0.05). After treatment, wheal duration, size and number as well as pruritus scores were markedly lower in SG than in CG, albeit non-significantly (p > 0.05). The levels of CD3+ CD4+, and CD4+/CD8+ ratio in SG after treatment were significantly higher than those in CG (p < 0.05). Furthermore, the serum IgE, IL-4 and IL-13 levels were significantly lower in SG than in CG, while the IFN-γ level was significantly higher (p < 0.05).
 Conclusion: Levocetirizine hydrochloride tablets produce a significant clinical curative effect on chronic urticaria relative to desloratadine citrate tablets. It reduces the levels of inflammatory factors and mitigates immune dysfunction in patients by increasing the serum level of total IgE. Therefore, it is a potential candidate for further clinical investigations on a larger and more diverse population.

Autoimmune Cytopenias Are Highly Associated with Inborn Errors of Immunity and They May Be the Initial Presentations in Cases without Severe Infections

Introduction: Inborn errors of immunity (IEIs) are inherited disorders that present with increased susceptibility to infections as well as noninfectious complications. Due to the aberrant immune functions of patients with IEI, autoimmune cytopenia (AIC) may be the initial finding, which makes diagnosis a challenge. We aimed to evaluate the clinical course, laboratory findings, and treatment response of AIC in children with IEI. Methods: Data of children with autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenic purpura (ITP) were obtained from a retrospective chart review of IEI patients diagnosed and followed in our center. Demographic and clinical features and therapeutic outcomes were evaluated. Immunologic findings were compared between patients with AIHA, ITP, and Evans syndrome (ES). The patients were also divided into two subgroups based on the presence or absence of immune dysregulation diseases (IDDs), and all data were compared between these two groups. Results: Out of 562 patients with IEI, 6% (n: 34) had AIC which were ITP (23.5%), AIHA (35.5%), and ES (41.2%). AIC was the initial finding in 50% of these 34 patients. Patients with ES had a higher mean percentage of CD8+ T lymphocytes than ITP patients (40.77 ± 20.21% vs. 22.33 ± 12.48%, p = 0.011). Patients with IDDs were more likely to develop ES (p = 0.004), lymphoproliferation (p = 0.005), and resistance to first-line therapy (p = 0.021) than other IEI groups. Conclusion: This study shows that AIC may be the initial finding of IEI, particularly when lymphoproliferation and resistance to first-line therapy co-occur. Therefore, detailed investigation should be offered to all patients to avoid diagnostic delay.

Focus on limbal stem cell deficiency and limbal cell transplantation.

Limbal stem cell deficiency (LSCD) causes severe vision impairment and can lead to blindness, representing one of the most challenging ocular surface disorders. Stem cell deficiency can be congenital or, more often, acquired. The categorization of ocular surface transplantation techniques is crucial to achieving treatment homogeneity and quality of care, according to the anatomic source of the tissue being transplanted, genetic source, autologous or allogenic transplantation (to reflect histocompatibility in the latter group), and cell culture and tissue engi neering techniques. The aim of this minireview is to provide a summary of the management of LSCD, from clinical characteristics and therapeutic outcomes to the development of novel therapeutic approaches. The manuscript also briefly summarizes recent findings in the current literature and outlines the future challenges to overcome in the management of the major types of ocular surface failure.

The clinical characteristics and therapeutic outcomes of adult patients with community-acquired spontaneous bacterial meningitis with a fulminant clinical course in Taiwan

PurposeTo examine the clinical characteristics of adult patients with community-acquired spontaneous bacterial meningitis (CASBM) with a fulminant clinical course.Materials and methodsThe clinical features and therapeutic outcomes of 127 adult CASBM patients were analyzed. The patients were divided into two groups as those with and without a fulminant clinical course. Fulminant clinical course was defined as meningitis presenting initially with marked consciousness disturbance (Glasgow Coma Scale score < 8) or a rapid deterioration in consciousness level within 48 h of hospitalization.ResultsAmong the 127 enrolled patients, 69 had a fulminant clinical course (47 men and 22 women) and 58 did not. The patients with a fulminant clinical course had a significantly higher incidence of end-stage renal disease (ESRD), severe clinical manifestations and higher mortality rate, and the survivors had significantly worse therapeutic outcomes. Klebsiella (K.) pneumoniae (50 strains) was the most important pathogen for the development of a fulminant clinical course, and all strains were susceptible to ceftriaxone and ceftazidime. With treatment, 50.7% (35/69) of the patients with a fulminant clinical course died, and the presence of K. pneumoniae infection was significant prognostic factor.ConclusionsThe presence of ESRD, initial presentation of altered consciousness, septic shock, seizures and CSF total protein level and K. pneumoniae infection were significantly associated with a fulminant clinical course of adult CASBM, and patients with this specific infectious syndrome had high mortality and morbidity rates. The presence of K. pneumoniae infection is a significant prognostic factor.

Clinical characteristics and therapeutic outcomes of acromegalic patients with giant growth hormone-secreting pituitary adenomas: a single-center study of 67 cases.

Acromegalic patients with giant growth hormone-secreting pituitary adenomas (GHPAs) (≥ 40mm) are relatively rare, and their clinical characteristics and treatment outcome data are limited. This study aims to analyze the clinical practice experience of giant GHPAs. Sixty-seven acromegalic patients with giant GHPAs and 67 patients with macro GHPAs (10-39mm), matched for age and gender from the same hospital during the same period, were retrospectively recruited. The clinical characteristics, treatment, and outcomes were analyzed. Enlargement of the extremities and facial features were the most common symptoms in most patients (92.5%). Compared with the macroadenoma group, more frequent visual impairment (86.6% vs. 25.4%, P < 0.001) and gonadal axis dysfunction (49.3% vs. 34.3%, P = 0.008), higher preoperative fasting GH, nadir GH after OGTT and IGF-1 levels, and a higher proportion of extrasellar tumor invasion were seen in the giant adenoma group. As the adenoma size increases, the total resection rate decreases, and postoperative complications and multimodal treatment strategies increase significantly. Fasting and nadir GH levels remained higher at 1week postoperatively, and there were more surgical complications and cases of anterior hypopituitarism in the giant group. After a median follow-up of 36months, 12 patients (36.4%) in the giant GHPA group and 17 (36.2%) in the macro GHPA group achieved biochemical remission. Other factors such as age of onset, age of diagnosis, delayed diagnosis time, metabolic complications, p53 positive rate, and Ki-67 index showed no significant difference between the two groups. With aggressive multimodal therapy, the biochemical remission rate of acromegalic patients with giant GHPAs is comparable to that of patients with macro adenoma. However, postoperative complications and hypopituitarism need to be closely monitored.

Hard-to-treat or hard-to-catch? Clinical features and therapeutic outcomes of help-seeking foster care youths with mood disorders.

The high level of emotional problems in youths placed in foster care contrasts with the limited use of evidence-based treatments. This study aims to better characterize the clinical features and therapeutic outcomes of foster care youths with mood disorders. A secondary analysis of data collected in the context of a French-Canadian clinical research network on pediatric mood disorders in four sites was conducted to compare three groups of patients with depressive or bipolar disorder: those without exposure to child welfare intervention (WCWI, n = 181), those who received non-placement psychosocial intervention (NPI, n = 62), and those in placement interventions (PI, n = 41). We observed a very high rate of academic problems in patients in the groups NPI/PI compared to those in the WCWI group. Patients in the PI group had more disruptive behavioral disorders (OR = 6.87, 95% CI [3.25-14.52]), trauma-related disorders (OR = 3.78, 95% CI [1.6-8.94]), and any neurodevelopmental disorders (OR = 2.73, 95% CI [1.36-5.49]) compared to the other groups (NPI/WCWI). Among inpatients, the Clinical Global Impression-Improvement scale and the change in the Children Global Assessment Scale during the hospital stay did not differ across the three groups. We observed a higher prescription rate of antipsychotics in the PI group compared to the NPI/WCWI groups, but no significant difference for antidepressants and mood stabilizers. These findings support the view that, when provided with dedicated support, fostered inpatient youths can improve in a range comparable to other inpatients. Undetected neurodevelopmental disorders and academic problems are likely important contributors of the burden of mood disorders in these youths.

Subtypes of borderline personality disorder in a day-clinic setting-Clinical and therapeutic differences.

This preliminary study aims at extending existing empirical evidence on subtypes of borderline personality disorders (BPDs) by identifying subtypes among patients with BPD, comparing their characteristics to the trait domains of the dimensional model of the International Classification of Diseases, 11th Revision (ICD-11; World Health Organization [WHO], 2022), and examining differences in sociodemographic, clinical, and therapeutic outcome variables. Data of N = 109 patients were subjected to cluster analysis based on the International Personality Disorder Examination variables for BPD and analyzed regarding differences in clinical and therapeutic variables. Clustering suggested a three-cluster solution, namely, internalizing (n = 35), externalizing (n = 28), and mixed subtype (n = 46). Subtypes showed differences in clinical variables and therapeutic outcomes with the internalizing showing more affective disorders and the mixed subtype showing the lowest therapeutic change in borderline-specific symptoms. Together, the present results correspond to the model of the ICD-11 (WHO, 2022). Clinical and treatment implications are being discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).