Clinical Treatment Outcomes Research Articles

Comparative Outcomes Between Three Different Techniques in the Fixation of Ulnar Styloid Fractures

Abstract Purpose This study aims to compare the clinical and radiological outcomes of three different techniques used in the surgical treatment of ulnar styloid fractures. Material and Method Ulnar styloid fractures treated surgically between 2012 and 2022 were evaluated retrospectively. There were three groups in the study: Group I (Kirschner wire, N= 19), Group II (tension band, N= 27) and Group III (headless compression screw, N= 25). The Gaulke classification was applied to categorise the fractures. After a follow-up period of at least one year, range of motion, Modified Mayo Wrist Score (MMWS), Quick Disabilities of the Arm, Shoulder and Hand Score (QDASH), Visual Analogue Scale (VAS) and grip strength were measured. In addition, radiological union, bone resorption and dorsal subluxation of the DRUJ were evaluated. Results There was no difference between the three groups in terms of demographic data. Gaulke type 2 A was more frequently observed in all three groups (47.4%, 74.1%, 64%, respectively). Range of motion (flexion, extension, supination, pronation) was similar in all three groups (p>0.05). QDASH and MMWS were similar in all three groups. Grip strength was significantly lower in Group I than in Group II (p=0.039). Radiological outcomes (nonunion, dorsal subluxation, bone resorption) were similar in all three groups. Implant irritation was significantly higher in Group II (p=0.026). Conclusion K-wires, tension band wiring and headless compression screws yield similar clinical and radiological outcomes in the surgical treatment of unstable ulnar styloid fractures. However, the need for secondary surgery is more frequent when a tension band is used. Level of Evidence: Level IV.

Prevalence and features of allergic bronchopulmonary aspergillosis, United States, 2016–2022

The epidemiology of allergic bronchopulmonary aspergillosis (ABPA) in the United States is not well-described. To estimate national ABPA prevalence among patients with asthma or cystic fibrosis, characterize ABPA testing practices, and describe ABPA clinical features, treatment, and 6-month outcomes. We used the 2016–2022 Merative™ MarketScan® Commercial/Medicare and Multi-State Medicaid Databases to identify cohorts of patients with 1) asthma, 2) cystic fibrosis (CF), and 3) ABPA. We calculated ABPA prevalence per 10,000 patients with asthma or CF, assessed diagnostic testing for ABPA among patients with severe asthma, and described features of patients with ABPA using diagnosis and procedure codes. The overall ABPA prevalence among patients with asthma was 2.8/10,000 (Commercial/Medicare) and 1.0/10,000 (Medicaid). ABPA prevalence increased with asthma severity (Commercial/Medicare: mild 1.3, moderate 9.3, severe 70.6, Medicaid: mild 0.3, moderate 2.4, severe 32.4). Among patients with CF, ABPA prevalence was 183.7/10,000 (Commercial/Medicare) and 134.6/10,000 (Medicaid). Among patients with severe asthma, 10.3% (Commercial/Medicare) and 7.4% (Medicaid) received total immunoglobulin E testing, which is recommended for ABPA diagnosis. Among all patients with ABPA (Commercial/Medicare: n = 1,564, Medicaid: n = 410), ABPA treatments included inhaled corticosteroids (>70%), systemic corticosteroids (>62%), and antifungals (>18%). Patients with ABPA and Medicaid were more likely to experience hospitalization (45.1% vs. 22.5% of patients with Commercial/Medicare insurance) and respiratory failure (18.5% vs. 10.9%). This analysis provides initial estimates of national ABPA prevalence. Further studies could identify potential barriers to ABPA testing and investigate potential factors affecting payer-related differences in ABPA burden.

Clinical Presentation, Treatment Outcomes, and Demographic Trends in Vestibular Schwannomas: A 135-Case Retrospective Study

Background: This study presents a comprehensive analysis of 135 cases of vestibular schwannoma (VS) treated between 2006 and 2022 at the National Institute of Neurology and Neurovascular Diseases in Bucharest, Romania. The investigation focuses on the clinical presentation, treatment outcomes, and demographic trends of VS patients, highlighting region-specific insights that fill critical gaps in Eastern European data. Methods: Patients were treated with either open surgery (93.3%) or gamma knife radiosurgery (6.6%). The study identifies predominant symptoms, including hearing impairment, facial palsy, and balance disorders, with variations observed across age and gender subgroups. Comorbidities such as hypertension and obesity were prevalent, and they influenced perioperative risks. Results: Post-treatment outcomes showed a significant correlation between clinical symptoms and treatment modalities, with a majority achieving favorable results. The findings emphasize the need for tailored approaches in VS management and underscore the importance of region-specific factors in influencing clinical outcomes. Conclusions: This study contributes to refining treatment strategies and improving healthcare delivery for VS patients in Romania and beyond.

Clinical outcome of BCG treatment for patients with urothelial carcinoma of the prostatic urethra: Implications for early cystectomy.

This study aimed to clarify the clinical outcomes of Bacillus Calmette-Guérin (BCG) treatment in patients with urothelial carcinoma (UC) of the prostatic urethra. Between August 2003 and January 2023, 428 patients with non-muscle-invasive UC received BCG treatment (Tokyo strain, 80mg, ≥ 5 times) in our hospital; 39 had UC of the prostatic urethra. We evaluated the cumulative incidence of intravesical recurrence, progression (muscle-invasive bladder cancer [MIBC] or metastasis), and subsequent radical cystectomy after BCG treatment in patients with UC of the prostatic urethra. The median follow-up period was 57months (interquartile range, 30-85months). The exact T stage of the patients with UC of the prostatic urethra was carcinoma in situ (CIS) in 29 (27 in the prostatic urethral mucosa and two in the ductal spread), Ta in 7, Ta + CIS in 2, and T1 in 1. All 39 patients had previous or concurrent bladder cancer. Patients with UC of the prostatic urethra experienced significantly higher rates of intravesical recurrence, progression (MIBC or metastasis), and subsequent radical cystectomy than those without UC of the prostatic urethra. In the multivariate analysis, UC of the prostatic urethra was a significant risk factor for progression (hazard ratio 4.06, 95% confidence interval 1.86-8.86, p < 0.001). This study reported the largest number of clinical outcomes after BCG treatment in patients with UC of the prostatic urethra. Concomitant UC of the prostatic urethra is a strong predictor of subsequent progression; therefore, early timing of radical cystectomy should be discussed.

The clinical characteristics and treatment outcomes of patients with systemic polyarteritis nodosa (PAN): a single centre study from India.

To describe the clinical profile and compare the long-term outcomes of patients with S-PAN treated with various treatment regimens at our centre in the last 2 decades. Data regarding clinical presentation, treatment allocation, relapses and outcomes of patients fulfilling American College of Rheumatology (ACR) 1990 criteria for PAN in the last 2 decades were recorded from electronic medical records. Relapse-free survival and predictors were analysed using KM survival statistics and regression analysis. Altogether, 53 patients including 2 with hepatitis B infection were included. Cutaneous lesions and peripheral neuropathy were the commonest manifestations. Most patients (64.2%) presented with a five-factor score (FFS) of 0. Disease-attributable hypertension and peripheral gangrene were the most common manifestations of severe disease. During a median follow-up period of 53.5 months in 49 patients, 43 (87.8%) attained complete response while 3(6.1%) had a partial response. Nineteen (40.4%) patients relapsed at a median duration of 82 (IQR 36.3-127.7) months. The relapse-free survival in patients who received induction with mycophenolate (n = 26), was comparable to that with cyclophosphamide (n = 21) [adjusted HR : 0.68]. Smoking history was an independent predictor of relapse (HR = 6.28, p= 0.013) while age was protective (HR = 0.94, p= 0.015). FFS and BVAS at 3 months were among the predictors of mortality (total deaths = 5). In our cohort of S-PAN, relapses were observed in 40.4% of patients. Mycophenolate was similar to cyclophosphamide in maintaining relapse-free survival. Only 10% fatality was recorded. FFS and BVAS at 3 months were predictors of mortality.

43 G > T polymorphism in the sucrase-isomaltase gene in the Chinese population prevents the glucose-lowering effect of acarbose.

Acarbose is an α-glucosidase inhibitor widely used clinically for its significant hypoglycemic effect, albeit with inter-individual variations in response. The sucrase-isomaltase (SI) enzyme is the primary target of acarbose. This study aims to investigate the impact of genetic polymorphisms in the SI gene on the pharmacodynamics of acarbose. The Illumina sequencing platform and variation-related databases were employed to analyze probable gene polymorphism sites of SI. Based on the SI polymorphism sites, Chinese subjects (n = 66) were categorized into the wild-type homozygous group (Group A) and the heterozygous variant group (Group B, SI 43 G > T). The validated hexokinase method was utilized to determine glucose concentrations in participants' serum samples. The differences in blood glucose concentration reduction and pharmacodynamic parameters peak concentration (Cmax) and area under the curve (AUC0-2h) after administering the same dose of acarbose were analyzed between the two groups of subjects. Our results showed that the mean changes in glucose Cmax, AUC0-2h, maximum increase, and maximum decrease in Group B were each lower by 67.66 %, 63.05 %, 53.17 %, and 50 % compared to Group A (all p < 0.05). These data suggested that genetic polymorphism of the SI gene can significantly influence the hypoglycemic efficacy of acarbose, and the polymorphism of SI is associated with individual differences in clinical treatment outcomes.

Ebstein's anomaly in children and young adults: clinical features, arrhythmia, surgical management, and factors affecting arrhythmia and mortality.

Ebstein's anomaly represents 40% of congenital tricuspid valve abnormalities. Studies about paediatric Ebstein's anomaly patients are limited. To evaluate clinical characteristics, treatment (medical/arrhythmia ablation/surgical) results, and outcome of Ebstein's anomaly patients, and to determine factors affecting arrhythmia presence and mortality. Clinical data, echocardiography, treatment results, and outcomes of patients followed in our centre between 2000 and 2017 were retrospectively evaluated. A total of 79 patients (61 children, median diagnosis age: 1.5 years [1 day-24 years]) were included. Eight patients (10.1%) were deceased during the study period. Common associated anomalies were atrial septal defect/patent foramen ovale (56.9%), mitral regurgitation (25.3%), pulmonary stenosis/atresia (17.7%), and ventricular septal defect (16.5%). Genetic diseases/congenital anomalies were present in 5/3.8%. Tricuspid regurgitation was present in 75.9%, and severe in 50%. Arrhythmias were detected in 30.4%, and accessory pathway-mediated re-entrant tachycardia was the most common (67%). Wolff-Parkinson-White syndrome was present in 12.7%. Twenty-one ablation procedures (radiofrequency ablation [85.7%]/cryoablation [14.3%]) were performed in 16 patients (median age: 13.3 years [4.9-17]). Acute success/recurrence rates: 87.5/25%. Surgery was performed in 31.6% (median age: 6.5 years [4 days-29 years]), 7.6% were operated during the first month, and 12.6% during the first year. Second surgery was required in 28%. Perioperative mortality rate was 12%, and median mortality age was 25 days (1 day-17 years). Median follow-up period was 5.3 years (1 day-32 years). Older diagnosis age (p = 0.005) and mild-moderate mitral regurgitation (p = 0.036) were associated with arrhythmias. Younger age at diagnosis (p = 0.012), younger age at first surgery (p = 0.004), surgery before age three years (p = 0.037), and presence of pulmonary atresia (p = 0.000014) were associated with mortality. Gender, diagnosis age, congenital anomalies/genetic disorders, tricuspid regurgitation, arrhythmias, and surgery history did not have an independent effect on survival. In children and young adults presenting with Ebstein's anomaly, younger age at presentation and at surgery, surgery before age three years, pulmonary atresia were associated with death. Ablation procedures can be successfully performed but recurrence rate is still high.

Four Decades of Treatment for Actinic Cheilitis: Outcomes, Challenges, and the Introduction of a New Clinical Index.

To evaluate the clinical outcomes of surgical and non-surgical treatments for actinic cheilitis (AC) over a four-decade period and to introduce a novel Clinical Index for the Treatment and Control of Actinic Cheilitis (CITC-AC) for improved patient stratification and management. A retrospective cohort study analyzed 151 patients diagnosed with AC treated at a university clinic between 1980 and 2020. Sociodemographic, clinical, and histopathological data were collected. Treatments were categorized as sun protection (SP), topical corticosteroids (TC), surgical removal (SR), and vermilionectomy. Therapeutic outcomes, recurrence rates, and malignant transformation were assessed. The CITC-AC was developed to guide clinical decision-making based on stratified risk. A total of 87% of patients achieved therapeutic resolution. Recurrence was observed in 13%, and malignant transformation occurred in 7% of cases. Surgical treatments, particularly vermilionectomy, demonstrated superior outcomes with no recurrence or malignancy. Non-surgical treatments, including the novel use of Omcion-A Orabase, achieved favorable outcomes but exhibited higher recurrence rates. The CITC-AC provided a structured framework for stratifying patients by severity and risk, aiding in the selection of appropriate interventions and follow-up schedules. This study highlights the importance of individualized treatment strategies and consistent follow-up in AC management. While surgical interventions remain the gold standard for advanced cases, non-surgical treatments are effective for early-stage lesions. The CITC-AC offers a practical tool for optimizing patient care and reducing progression to squamous cell carcinoma (SCC). Prospective studies are needed to validate its applicability across diverse clinical settings.

Papulonodular mucinosis: a systematic review on clinicopathologic characteristics, course and treatment options.

Papulonodular mucinosis (PNM) is a rare cutaneous mucinosis recognized as a rare variant of lupus erythematosus. There are no large-scale cohort studies characterizing its clinicopathological features or evaluating the effectiveness of various treatment options. This study aimed to review the literature on PNMs to identify its clinical and histological features and treatment outcomes. The search includes studies from the PubMed, Embase, and Cochrane Library databases up to the March 1, 2024. A total of 37 studies, encompassing 44 patients, were included in the review. Of these, 20 were males and 24 females, with a mean age at diagnosis of 34.9 ± 1.92years. PNM lesions are characterized by generalized papules, plaques, and nodules, and histopathologically, they show abundant mucin deposition throughout the dermis. The temporal relationship between PNM and SLE is variable. There is no evidence that SLE patients with PNM are more prone to organ involvement or increased disease activity. A combination of medical history, clinical features, and histopathological findings is essential for diagnosis; however, misdiagnosis is possible until lupus erythematosus (LE) becomes evident. Hydroxychloroquine and systemic glucocorticoids are the current mainstays of treatment for PNM, with most patients achieving partial or complete remission.

Clinical Outcomes in a Large Sample of Youth and Adult Patients Receiving Virtual Evidence-Based Treatment for ARFID: A Naturalistic Study.

Treatment outcomes research for avoidant/restrictive food intake disorder (ARFID) has been limited to small,mixed-age feasibility trials in face-to-face care settings. This study aims to examine clinical characteristics and treatment outcomes in a large sample of youth and adult patients receiving virtual multidisciplinary team treatment for ARFID. The sample included N = 783 patients (532 youth and 251 adults) diagnosed with ARFID. Patients received cognitive behavioral therapy for ARFID (CBT-AR) or family-based treatment for ARFID (FBT-ARFID) enhanced by specialized support from a multidisciplinary team. Patients (or caregivers) completed a number of measures assessing ARFID and mood-related symptoms upon admission and throughout treatment. Youth patients on weight restoration (56%) started treatment around 85% [84%, 86%] of their target weight, and increased to 94% [93%, 96%] by week 35. Adults on weight restoration (47%) started at 85% [84%, 87%] and reached 92% [90%, 94%]. Scores improved for both groups on all PARDI-AR-Q subscales: (sensory sensitivity: b = -0.25 [-0.33, -0.16]; lack of interest: b = -0.08 [-0.16, -0.00]; fear of aversive consequences: b = -0.12 [-0.19, -0.04]). Both youth and adults demonstrated reliable improvements in willingness to try new foods (b = -0.64 [-0.89, -0.37]), anxiety symptoms (b = -0.71 [-0.95, -0.48]), and depression symptoms (b = -0.86 [-1.07, -0.64]). Youth and adult patients demonstrated reliable symptom improvements over the course of treatment across all measures, offering preliminary support for the effectiveness of FBT-ARFID and CBT-AR delivered virtually by a multidisciplinary care team.

Acne Conglobata: Insights into Severe Nodulocystic Acne and Novel Therapeutic Approaches

Background: Acne Conglobata (AC) is a rare and severe form of nodulocystic acne, primarily affecting adolescents and young adults. Characterized by deep nodules, abscesses, and interconnected sinus tracts, AC often leads to significant scarring and psychological distress. Despite its rarity, it presents a unique challenge in resource-limited settings like Bangladesh, where awareness and specialized dermatological care are insufficient. The multifactorial etiology includes hormonal imbalances, genetic predisposition, and environmental factors, complicating both diagnosis and treatment. Objective: This study aims to provide comprehensive insights into the clinical characteristics, risk factors, comorbidities, and treatment outcomes of Acne Conglobata in Bangladesh, with a focus on emerging therapeutic modalities. Methods: A cross-sectional observational study was conducted at a tertiary hospital in Dhaka, Bangladesh, from January to December 2024. A total of 50 patients diagnosed with Acne Conglobata were included, with data collected through clinical evaluations, patient interviews, and medical records. Descriptive statistics were employed to analyze demographic variables, risk factors, comorbidities, and treatment outcomes. Results: The majority of patients were aged 17-30 years, with a higher prevalence in males (70%). Hormonal imbalances (especially during puberty) and a family history of acne were the most common risk factors. Comorbidities such as depression/anxiety (40%), obesity (30%), and insulin resistance (20%) were prevalent. Treatment regimens primarily involved oral isotretinoin (80%), oral antibiotics (60%), and steroids (50%). Scar revision procedures were used in 30% of cases. Conclusion: Acne Conglobata significantly impacts young adults in Bangladesh, with genetic, hormonal, and environmental factors playing key roles in its pathogenesis. Depression, obesity, and insulin resistance were common comorbidities. Oral isotretinoin remains the most effective treatment, but a multimodal approach, including psychological support and scar revision, is essential. This study highlights the need for increased awareness and access to advanced therapies, especially in resource-limited settings like Bangladesh.

Clinical characteristics and outcomes of biliary atresia in the eastern province of Saudi Arabia: 26-years single-center experience

Objective: This study aimed to evaluate the clinical characteristics and treatment outcomes of biliary atresia (BA) in the Eastern Province of Saudi Arabia. Methods: A retrospective analysis was performed on data collected from August 2023 to January 2024 for patients who received an intraoperative BA diagnosis in the last 26 years. Perioperative data, clinical presentation, investigations, Kasai portoenterostomy (KPE) course, complications, and outcomes were collected. Primary outcomes included BA clinical features, diagnosis, and KPE timing impact on KPE success, postoperative steroid use, and native liver survival (NLS). Results: Eight children (three females, five males) were included. Seven were Saudi. All exhibited jaundice in the initial presentation. Three patients had G6PD deficiency, one had sickle cell trait, one had alpha thalassemia, one had hemophilia B, and one had microcytic hemolytic crisis. The average age at presentation was 36 ± 16.5 days. Six patients underwent KPE and three were eligible for liver transplant. The average age at the time of the KPE was 50.6 ± 8.18 days, and all received steroids afterward. None of the patients cleared their jaundice at 6 months. Two patients remain alive, the rest were lost to follow-up. Conclusions: KPE before 60 days and post-operative steroids did not influence KPE success, highlighting the potential need for earlier detection and intervention. This research revealed a high prevalence of hematological diseases in this population.

MOG IgG antibody positivity from laboratory to clinical practice: A real world experience.

Myelin oligodendrocyte glycoprotein (MOG) associated disease (MOGAD) is an antibody-mediated inflammatory demyelinating disorder of the CNS with varied presentations like optic neuritis (ON), transverse myelitis, and cortical encephalitis. This study aims to highlight the significance of low MOG IgG antibody positivity and its diagnostic implications in a real-world cohort. In this retrospective observational study, serum and CSF from suspected MOGAD cases were tested at a tertiary healthcare centre's Neuroimmunology Laboratory. MOG autoantibodies were detected using a EUROIMMUN commercial kit, and seropositivity was determined by visual agreement of fluorescence by two trained observers. Patient data were retrieved from Electronic Medical records. Out of 103 MOG IgG seropositive patients, 95 were included in the final analysis (Mean age: 32.47±4.63 years; 42 males, 53 females; 36 pediatric, 59 adult) after excluding those with alternate diagnoses. The most common clinical event was ON (37.89%). The 2023 International MOGAD Diagnostic Criteria was met by 35/67 low-strength and 27/28 high-strength patients. Adults were more likely to have atypical presentations and low serum MOG levels. Pediatric patients had better EDSS at discharge but relapsed more. There were no significant differences between low and high positive groups in terms of treatment received, EDSS, relapse, or outcome. Low and high levels of MOG seropositivity showed similar diagnostic value in terms of clinical features, treatment outcome, and prognosis, except for age distribution. Many patients exhibited low-strength positivity and atypical disease presentations, requiring strong clinical judgement for diagnosis.

Clinical characteristics and treatment outcomes of patients with insulinoma–a single center's experience of 76 cases over a 10-year period

Clinical characteristics and treatment outcomes of patients with insulinoma–a single center's experience of 76 cases over a 10-year period

A new distal radius fracture classification depending on the specific fragments through machine learning clustering method

PurposesThe objective of this study was to investigate intra-articular distal radius fractures, aiming to provide a comprehensive analysis of fracture patterns and discuss the corresponding treatment strategies for each pattern.Methods294 cases of intra-articular distal radius fractures lines were collected and clustered thorough K-means and hierarchical clustering algorithm. The demographic data of patients and the clinical treatment outcomes were recorded. For functional evaluation, quick Disabilities of the Arm, Shoulder, and Hand (DASH) score, visual analog scale (VAS) pain score, range of motion (ROM) of the wrist joint and the percentage of the grip strength relative to the healthy wrist at 12 months follow-up were evaluated and recorded; For radiographic parameters of volar tilt (VT), radial inclination (RI), and ulnar variance (UV) were obtained; The occurrence of complications was carefully assessed and documented.ResultsTotally 294 patients were included and divided into the volar side affected group and the dorsal side affected groups. And each group was further categorized into three types: type I, with two parts fractures with either one volar/dorsal side intact; type II, with three parts fractures with volar/dorsal side simply affected; and type III, with four parts fractures with volar/dorsal side communited affected. The volar plate fixation was performed as the standard treatment, while the combined plate fixation was used for comminuted dorsal bone defects of the metaphysis and impaction. There were no differences in the postoperative radiograph parameters, functional outcomes and incidences of complications for each type of volar side group and dorsal side group except that the 3.2 type DRFs showed less range of flexion (75.56±7.48)° and extension (61.65±9.9)° than other dorsal types.ConclusionsA new intra-articular distal radius fractures classification was proposed based on the affection condition of volar or dorsal side. The volar plate fixation is an effective treatment for the intra-articular distal radius fractures, while combined plate fixation can be considered as an alternative treatment for dorsal side comminuted fractures.Level of evidenceIII a

Association of Clinical Profile and Treatment Outcomes of Pediatric Patients with Anaphylaxis from 2018 to 2022 in Ospital ng Makati

Objective: To evaluate the association between clinical profiles, including symptom presentation, medical history, triggers, and comorbidities; clinical outcomes, such as admission to ICU or ward, mortality, and biphasic anaphylaxis in pediatric patients aged 0-18 years old admitted for anaphylaxis at Ospital ng Makati - Department of Pediatrics from January 2018 to December 2022 Methodology: This cross-sectional study utilized a retrospective chart review of pediatric patients aged 0 to 18 years who were admitted for anaphylaxis during the study period. Patient confidentiality was maintained throughout the review. Demographic and clinical characteristics were recorded and summarized using descriptive statistics. The association between demographic characteristics, clinical profile, management, and outcomes was assessed using the Chi-square or Fisher’s exact test, with odds ratios calculated as the measures of association. Results: From 2018 to 2022, 97 pediatric patients were diagnosed with anaphylaxis. Food was the most common trigger (86.6%), followed by medications (9.3%). The majority of patients presented with skin/mucosal involvement (97.9%), respiratory compromise (61.9%), and gastrointestinal symptoms (36.1%). Respiratory compromise (p = 0.001) and cardiovascular instability (p = 0.010) were associated with severe outcomes, including ICU admission. A history of atopy (p = 0.002) was linked to biphasic anaphylaxis. Conclusion: This study highlights the increasing incidence of anaphylaxis in older age groups, with food being the most common etiology. Respiratory compromise and cardiovascular instability are predictors of severe outcomes of anaphylaxis, emphasizing the importance of detailed patient history and prompt management in such cases.

Integrating immune multi-omics and machine learning to improve prognosis, immune landscape, and sensitivity to first- and second-line treatments for head and neck squamous cell carcinoma

In recent years, immune checkpoint inhibitors (ICIs) has emerged as a fundamental component of the standard treatment regimen for patients with head and neck squamous cell carcinoma (HNSCC). However, accurately predicting the treatment effectiveness of ICIs for patients at the same TNM stage remains a challenge. In this study, we first combined multi-omics data (mRNA, lncRNA, miRNA, DNA methylation, and somatic mutations) and 10 clustering algorithms, successfully identifying two distinct cancer subtypes (CSs) (CS1 and CS2). Subsequently, immune-regulated genes (IRGs) and machine learning algorithms were utilized to construct a consensus machine learning-driven prediction immunotherapy signature (CMPIS). Further, the prognostic model was validated and compared across multiple datasets, including clinical characteristics, external datasets, and previously published models. Ultimately, the response of different CMPIS patients to immunotherapy, targeted therapy, radiotherapy and chemotherapy was also explored. First, Two distinct molecular subtypes were successfully identified by integrating immunomics data with machine learning techniques, and it was discovered that the CS1 subtype tended to be classified as “cold tumors” or “immunosuppressive tumors”, whereas the CS2 subtype was more likely to represent “hot tumors” or "immune-activated tumors". Second, 303 different algorithms were employed to construct prognostic models and the average C-index value for each model was calculated across various cohorts. Ultimately, the StepCox [forward] + Ridge algorithm, which had the highest average C-index value of 0.666, was selected and this algorithm was used to construct the CMPIS predictive model comprising 16 key genes. Third, this predictive model was compared with patients’ clinical features, such as age, gender, TNM stage, and grade stage. The findings indicated that this prognostic model exhibited the best performance in terms of C-index and AUC values. Additionally, it was compared with previously published models and it was found that the C-index of CMPIS ranked in the top 5 among 94 models across the TCGA, GSE27020, GSE41613, GSE42743, GSE65858, and META datasets. Lastly, the study revealed that patients with lower CMPIS were more sensitive to immunotherapy and chemotherapy, while those with higher CMPIS were more responsive to radiation therapy and EGFR-targeted treatments. In summary, our study identified two CSs (CS1 and CS2) of HNSCC using multi-omics data and predicted patient prognosis and treatment response by constructing the CMPIS model with IRGs and 303 machine learning algorithms, which underscores the importance of immunotherapy biomarkers in providing more targeted, precise, and personalized immunotherapy plans for HNSCC patients, significantly contributing to the optimization of clinical treatment outcomes.

TMS-induced modulation of brain networks and its associations to rTMS treatment for depression: a concurrent fMRI-EEG-TMS study.

Transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (L-DLPFC) is an established intervention for treatment-resistant depression (TRD), yet the underlying therapeutic mechanisms remain not fully understood. This study employs an integrative approach that combines TMS with concurrent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), aimed at assessing the acute/immediate effects of TMS on brain network dynamics and their correlation with clinical outcomes. Our study demonstrates that TMS acutely modulates connectivity within vital brain circuits, particularly the cognitive control and default mode networks. We found that the baseline TMS-evoked responses in the cognitive control and limbic networks significantly predicted clinical improvement in patients receiving a novel EEG-synchronized repetitive TMS treatment. Furthermore, this study explored the brain-state dependent effects of TMS, as the brain-state indexed by the phase of EEG prefrontal alpha oscillation. We found that clinical outcomes in this novel treatment are linked to state-specific TMS-modulated functional connectivity within a pivotal brain circuit of the L-DLPFC and the posterior subgenual anterior cingulate cortex within the limbic system. These findings contribute to our understanding of the therapeutic effects underlying TMS treatment in depression and support the potential of assessing state-dependent TMS effects in TMS timing target selection. This study emphasizes the importance of personalized timing of TMS for optimizing target engagement of specific clinically relevant brain circuits. Our results are crucial for future research into the development of personalized neuromodulation therapies for TRD patients.

Pharmacokinetic/pharmacodynamic analysis of meropenem and fosfomycin combinations in in vitro time-kill and hollow-fibre infection models against multidrug-resistant and carbapenemase-producing Klebsiella pneumoniae.

MDR Gram-negative bacteria, such as ESBL-producing and carbapenemase-producing Klebsiella pneumoniae, represent major global health threats. Treatment options are limited due to increasing resistance and slowed development of novel antimicrobials, making it necessary to apply effective combination therapies based on approved antibiotics. To quantitatively evaluate the synergistic potential of meropenem and fosfomycin against carbapenem-resistant K. pneumoniae strains isolated from clinics. We evaluated four MDR K. pneumoniae strains, each expressing KPC-2 or KPC-3, using static time-kill assays that accounted for measured meropenem degradation. This was followed by pharmacokinetic/pharmacodynamic (PK/PD) interaction modelling, which estimated meropenem degradation rate constants and identified perpetrator-victim relationships in PD interactions. Dynamic hollow-fibre infection model (HFIM) experiments were used to confirm synergy. Static time-kill assays demonstrated high killing effects and suppressed regrowth for the combination of meropenem and fosfomycin, compared with the failure of monotherapy. Meropenem degradation was significantly higher in the presence of bacteria, attributable to carbapenemase activity. Pharmacometric models indicated a synergistic interaction primarily driven by meropenem as the perpetrator, enhancing the potency of fosfomycin. HFIM experiments confirmed in vitro synergy, demonstrating continuous bacterial suppression of the combination therapy. Meropenem and fosfomycin exhibited additive or synergistic potential against carbapenemase-expressing single- or double-resistant K. pneumoniae at clinically achievable concentrations. This combination therapy may offer a strategy against MDR infections, possibly improving clinical treatment outcomes. Further in vivo research is needed to translate these findings into clinical practice, emphasizing the importance of PK/PD modelling in rationalizing antibiotic use.

Vasculitic Myopathy: Clinical Characteristics and Long-Term Outcomes.

Peripheral neuropathy is a common manifestation of systemic and nonsystemic vasculitides; however, there is limited literature on vasculitic myopathy. We aim to describe the clinical, laboratory, and pathologic characteristics and treatment outcomes of vasculitic myopathy. A retrospective chart review of patients with a diagnosis of vasculitis and myopathy (1980-2022) was performed. Patients were included with either biopsy-proven vasculitic myopathy or biopsy-proven vasculitis (of nonmuscle tissue) and concomitant active myopathy after excluding alternative causes. All muscle biopsy slides were reviewed, and additional immunohistochemistry studies were performed. Twenty-five patients with vasculitic myopathy were identified, 60% were female, and the median age at diagnosis was 63 (interquartile range 38-81) years. Ten patients (40%) had a primary systemic vasculitis, 12 secondary systemic vasculitis (48%), and 3 had nonsystemic vasculitic myopathy (12%). Myopathy was the initial manifestation of vasculitis in 20 of 25 patients (80%). Weakness was proximal and symmetric in most cases. Nineteen patients (76%) had pain at presentation: 2 with only neuropathic pain, 10 with only myalgia, and 7 had a combination of neuropathic pain distally and myalgia proximally. Creatine kinase (CK) was elevated in 3 of 23 patients (13%) and aldolase elevated in 10 of 16 patients (63%). Electromyography revealed short duration motor unit potentials in proximal and axial muscles in 23 of 24 patients (96%) and superimposed peripheral neuropathy in 15 of 24 (63%). Muscle biopsy showed perivascular inflammation in all biopsies, vessel wall inflammation and destruction in 18 of 21 (86%), and fibrinoid necrosis in 13 of 21 biopsies (62%). Masson trichrome stain facilitated the detection of fibrinoid necrosis. All muscle specimens had increased major histocompatibility complex class I sarcolemmal reactivity in nonnecrotic fibers. In most patients, the inflammatory infiltrates were predominantly CD4+ T cells, with complement deposition on blood vessels in some. Twenty-four patients improved with immunotherapy, and only 3 patients relapsed. Seven patients died during the study period, 1 from vasculitis complications. Probability of survival at 1 and 5 years was 96% and 84%, respectively. Myopathy can be the initial manifestation of a primary or secondary systemic vasculitis or may occur as a nonsystemic form. Most patients present with proximal predominant weakness with normal CK and elevated aldolase levels. Patients usually respond well to immunotherapy.