Cohort Of Patients Research Articles

Ictal Involvement of the Pulvinar and the Anterior Nucleus of the Thalamus in Patients With Refractory Epilepsy.

Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) has been shown to be effective in treating some patients with medically refractory epilepsy. However, it remains unknown how seizures spread through the ANT relative to other thalamic nuclei. This study aimed to investigate, through simultaneous recordings from both ANT and pulvinar (PLV) nucleus, their roles in seizure propagation. Our goal was to determine whether the ANT is the primary site of seizure propagation in the human thalamus, especially for focal seizure originating in the medial temporal lobe. In a retrospective design, we studied EEGs and clinical notes of patients with refractory epilepsy who were implanted with stereo-EEG (sEEG) electrodes across cortical regions, some of which were extended to reach various sites of the thalamus (i.e., multisite thalamic recordings). We selected patients from the Stanford Comprehensive Epilepsy Center with both ANT and PLV electrodes and collected information about the timing and anatomy of seizure activity in the seizure onset zones, usually temporal, and the 2 thalamic sites. We recruited 17 (5 female, mean age 32 years) adult patients with simultaneous ipsilateral ANT and PLV recordings. In all patients, the procedure was safe without any complications. In 100% of patients, the thalamus was involved during seizures (in 88% both ANT and PLV and in 82% first the PLV). In patients with confirmed hippocampal or amygdalar onset seizures, 62% had initial involvement and 100% had subsequent involvement of the PLV nucleus. Only 31% showed initial propagation to ANT. All focal-to-bilateral tonic-clonic seizures and most of the focal impaired awareness seizures had early involvement of both ANT and PLV, with rapid spread to the contralateral nuclei. sEEG of thalamic nuclei simultaneously provides an opportunity to understand propagation patterns of seizures with respect to each thalamic subdivision at the individual level. The patterns of seizure propagation, as we report here, provide insights about the prominent involvement of the PLV nucleus during seizure propagation. This may motivate future prospective work in larger cohorts of patients to understand how thalamic propagation may predict response to resective/ablative surgery or whether personalization of DBS (for instance, PLV instead of, or together with, ANT) could improve clinical outcomes.

Multimodal Assessment of the Origin of Myoclonus in Lance-Adams Syndrome.

Lance-Adams syndrome (LAS), or chronic posthypoxic myoclonus, is a long-term disabling neurologic disorder occurring in survivors of anoxia. The cortical or subcortical origin of this myoclonus is unclear. We aimed to identify the neuroanatomical origin of myoclonus in LAS. We conducted a cross-sectional study and investigated patients diagnosed with LAS from the Department of Neurology of Pitié-Salpêtrière Hospital, using multimodal neurologic explorations: EEG with quantitative analyses, polygraphic EMG recording of myoclonus, coupled EEG-EMG analyses with jerk-locked back averaging, and 18fluorodeoxyglucose PET/CT imaging. All 18 patients had action multifocal or generalized myoclonus. Eleven patients also presented seizures, mainly generalized tonic-clonic seizures. For 8 patients, myoclonus decreased after seizures for a variable duration, from 1 day to 2 weeks. Epileptiform discharges were identified over the central median region (n = 14), with a maximal amplitude on the Cz (65 ± 20 µV, n = 12) and Fz (107 µV, n = 1) electrodes, and a significantly increased frequency during non-rapid eye movement sleep stages 1 (12 ± 8.5 events/minute, p = 0.004, n = 9) and 2 (11 ± 8.8 events/minute, p = 0.016, n = 7) compared with wake (5.5 ± 5.4 events/minute). The duration of the cortical and muscular events was significantly and positively correlated (ρ = 0.58, p < 0.001, n = 9). Action myoclonic jerks with a duration of <50 ms were confirmed in all patients, with a fast-descending corticospinal way organization with a mean biceps brachii-first interossei dorsalis delay of 9.8 ± 1 ms (n = 8). A central cortical transient preceding the muscular jerks was identified (n = 14), with a mean latency of -31.9 ± 2.9 ms for the tibialis anterior muscle (n = 7). A regional metabolism decrease was observed in the precentral cortex, supplementary motor area, paracentral lobule (n = 6), and postcentral cortex and precuneus (n = 5). This metabolism decrease was bilateral in the precentral cortex for 83% of the patients and in the postcentral cortex for 100%. Hypometabolism in the precentral, supplementary motor, and postcentral areas was confirmed with a voxelwise analysis (p < 10-3, n = 6). Our findings, based on a large cohort of patients with LAS, strongly suggest a cortical myoclonus, originating within the motor cortex and related to epileptiform mechanisms.

Modifiable Risk Factors for Subarachnoid Hemorrhage: Narrative Review With an Emphasis on Common Controversies and Epidemiologic Pitfalls.

Given the relatively low incidence, high prehospital death rate, substantial geographical differences, and complex disease origin (combination of genetic and environmental risk factors), epidemiologic research on subarachnoid hemorrhage (SAH) and its risk factors is challenging. In practice, we are more or less forced to exploit compromised study designs and nonrepresentative data in such circumstances where it is almost impossible to gather comprehensive data through an optimal design. For example, hospital-based patient cohorts, administrative data repositories, and short-term population-based studies from small geographical regions are often used to research the incidence, case fatality, and risk factors of SAH, regardless of their inherent and self-evident limitations. Since studies on the epidemiology of SAH focus largely on identifying possible risk factors that could aid in disease diagnostics, treatment, and prevention, we aimed to review recent evidence on modifiable risk factors for SAH. In this context, we also try to explain the methodological reasons behind some of the conflicting results and to discuss the primary strengths and limitations of different study designs used in the field of SAH epidemiology. Based on our findings, smoking, high blood pressure, and possibly low physical activity are the only risk factors with high-quality evidence supporting their causal role in SAH. In addition, since all 3 commonly used study designs in SAH epidemiology, namely, hospital-based, population-based, and administrative register-based studies, have their own strengths and limitations, the most robust risk factor estimates and other epidemiologic measures of SAH can likely be established by combining various overlapping and high-quality sources of information in the future.

Outcomes of concurrent and delayed leadless pacemaker implantation following extraction of infected cardiovascular implantable electronic device.

The optimal reimplantation strategies following the removal of infected cardiovascular implantable electronic devices (CIEDs) remain inadequately understood. Given the limitations and risks associated with traditional approaches, the investigation of alternative devices, such as leadless pacemakers (LPs), has gained attention due to their potentially lower infection risk. We reviewed literature sources including PubMed, Scopus, and Embase, utilizing a combination of search terms. The inclusion criterion was leadless pacemaker (LP) implantation following lead removal (LR) of infected CIEDs, while the exclusion criterion was LR for noninfectious indications. Study endpoints encompassed patient outcomes during follow-up. Our literature review yielded 827 articles, of which 22 met the inclusion criteria, encompassing a cohort of 657 patients who underwent LR followed by LP implantation. A total of 295 (44.9%) patients underwent concurrent LP implantation during the LR procedure. The rest underwent delayed procedures, and the overall duration between LR of infected CIED and LP implantation was 4.32 ± 3.9days. A total of 194 (29.5%) patients had systemic CIED infections, whereas 153 (23.3%) had isolated pocket infections. In our patient cohort, procedural complications were scarce. Over a mean follow-up period of 13.3 ± 9.4months, pacemaker syndrome was observed in 4 patients (0.61%), and 3 patients (0.46%) experienced persistent or recurrent infections. Our review finds both concurrent and delayed LP implantation after infected CIED extraction to be safe, with low reinfection rates and minimal complications. LPs could also serve as a bridge to CRT re-implantation minimizing the use of temporary pacing systems.

DAIR for periprosthetic joint infections—One week to save the joint?

BackgroundPredicting the success of a Debridement, Antibiotics, and Implant Retention (DAIR) procedure for periprosthetic joint infection (PJI) for hip and knee joint arthroplasty remains a challenge. A failed DAIR might adversely affect the outcome of any future revision surgery for PJI. Hence, the ability to identify and optimize factors predictive of DAIR success would help target the procedure to the appropriate patient cohort and avoid unnecessary surgery for patients where a DAIR is unlikely to eradicate infection.MethodsA retrospective review of our prospective Bone Infection Group database was performed to identify all patients who underwent a DAIR of their primary or revision hip or knee arthroplasty. All patients had a confirmed PJI as per MSIS 2013 criteria and an outcome according to the MSIS working group outcome-reporting tool. DAIR surgery was then grouped into groups of “successful” or “unsuccessful” outcomes.ResultsSixty-four consecutive patients with an acute PJI underwent a DAIR procedure between 2009 and 2020, with 46 procedures performed for knees and 18 for hips. Treatment was successful in 69% (37 knees and 7 hips). The chance of a successful DAIR was significantly greater if performed at or within one week of symptom onset compared to greater than one-week duration (adjusted odds ratio (OR) 0.11; P = 0.027; 95% CI [0.02–0.78])). For DAIR performed at or within one week of symptom onset, the success rate was 93% for knees and 80% for hips. The chance of a successful DAIR however was not influenced by whether the surgeon was an arthroplasty or non-arthroplasty surgeon (OR 0.28; P = 0.13; 95% CI [0.05–1.48])). Isolated Streptococcus infection had a success rate of 100%. Next came Coagulase-negative Staphylococci (71%) and Methicillin-susceptible Staphylococcus Aureus (65%). Polymicrobial infection had the worst outcome, with a success rate of 40%.ConclusionIn our experience, DAIR surgery performed within one week of symptom onset significantly increased the chance of successful infection eradication. Collaborative work is required to ensure arthroplasty patients can access prompt appropriate surgical decision-making as soon as concerns arise, remove barriers to early assessment and minimise delays to surgery.

What are the views of those participating in a trial investigating acute post-traumatic benign paroxysmal positional vertigo? A qualitative study

ABSTRACT Objective The purpose of this study was to explore the experiences of patients and healthcare professionals participating in a randomized feasibility trial exploring the management of acute post-traumatic benign paroxysmal positional vertigo (BPPV), and to establish the acceptability and tolerability of BPPV assessment and treatment procedures. Methods This was a multi-center qualitative study nested within a wider randomized feasibility trial. Purposive sampling was used to gather a cohort of healthcare professionals and patients from three major trauma centres in London, UK. Data were gathered using semi-structured interviews and were analyzed using Framework analysis. Results Fifteen healthcare professionals and 26 patients participated. Patients and healthcare professionals reported acute BPPV diagnosis was acceptable and practicable. However, divergence was noted regarding views of randomization. Participants proposed several research delivery and protocol modifications for a future trial, including changes to study design and outcome measures. Conclusions Healthcare professionals and patients participating in a multi-center qualitative study felt post-traumatic BPPV was feasible and acceptable to diagnose and treat acutely. Findings from this study will enhance the content and delivery of a future trial and may assist in influencing the development of clinical practice guidelines.

Long-Term Outcomes in Patients With Chronic Total Occlusion and Left Ventricular Systolic Dysfunction - A Single-Center Inverse Probability of Treatment Weighting Analysis.

The optimal treatment strategy for patients with coronary chronic total occlusion (CTO) and left ventricular systolic dysfunction (LVSD) remains unclear. This study investigated the long-term outcomes of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and medical therapy (MT) in this specific patient cohort. This retrospective cohort study included 987 consecutive patients with CTO and LVSD who met the inclusion criteria and underwent either CTO-PCI (n=277), CTO-CABG (n=222), or CTO-MT (n=488) between 2014 and 2020. The primary outcome was all-cause mortality during follow-up. Secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE) and their components, including cardiovascular mortality, myocardial infarction (MI), stroke, unplanned revascularization, and hospitalization for heart failure. During a median follow-up of 5.3 years, 232 (23.51%) patients died from any cause. In the unadjusted analysis, CTO-MT was associated with worse long-term survival prospects. After inverse probability of treatment weighting and variable adjustment, CTO-PCI and CTO-CABG demonstrated significant reductions in the long-term risks of all-cause and cardiovascular mortality. Notably, CTO-CABG was associated with the lowest long-term risks of MACCE, MI, unplanned revascularization, and hospitalization for heart failure. For patients with CTO and LVSD, successful CTO revascularization significantly improved long-term survival compared with CTO-MT. CTO-CABG can be regarded as the optimal treatment modality for better long-term prognosis.

Evaluation of older patients with minor blunt head trauma to identify those who do not have clinically important traumatic brain injury and can be safely managed without cranial computed tomography.

Our primary aim was to identify a low-risk subgroup of older adults (aged 65 and older) presenting to ED with minor head trauma which can be safely managed without a cranial CT (cCT). This was a single-site, prospective, observational, cohort study conducted at a major-referral ED. Alert, haemodynamically stable, older adults with suspected head trauma were eligible. This included both community dwellers and residential aged care facility (RACF) residents. Primary outcome was the proportion of patients who had a clinically important traumatic brain injury (ciTBI) within 42 days of index ED presentation. Secondary outcomes included proportion investigated with a cCT, and proportion needing neurosurgical intervention. Two hundred seventy-six patients (mean age 80.5 years; 53.6% female) were enrolled. The most common mechanism of injury was ground-level fall (93.8%). One in four patients was from RACFs, 30.1% had dementia and 52.2% were on blood thinners. 80.8% had a cCT during the index ED visit. Seven (2.5%) patients had ciTBI within 42 days of index ED presentation. Patients with ciTBI had either external signs of head injury or abnormal neurological exam. All patients with ciTBI were treated conservatively after shared decision-making. Alert, haemodynamically stable, older ED adults with suspected head trauma had a low incidence of ciTBI in the present study. Abnormal physical examination findings were consistently present in patients with ciTBI. Shared decision-making prior to cCT may be the pragmatic way ahead in the management of this patient cohort, especially among those from RACFs.

Diverse NKT cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation.

Neurological injury drives most deaths and morbidity among patients hospitalized for out-of-hospital cardiac arrest (OHCA). Despite its clinical importance, there are no effective pharmacological therapies targeting post-cardiac arrest (CA) neurological injury. Here, we analyzed circulating immune cells from a large cohort of patients with OHCA, finding that lymphopenia independently associated with poor neurological outcomes. Single-cell RNA sequencing of immune cells showed that T cells with features of both innate T cells and natural killer (NK) cells were increased in patients with favorable neurological outcomes. We more specifically identified an early increase in circulating diverse NKT (dNKT) cells in a separate cohort of patients with OHCA who had good neurological outcomes. These cells harbored a diverse T cell receptor repertoire but were consistently specific for sulfatide antigen. In mice, we found that sulfatide-specific dNKT cells trafficked to the brain after CA and resuscitation. In the brains of mice lacking NKT cells (Cd1d-/-), we observed increased inflammatory chemokine and cytokine expression and accumulation of macrophages when compared with wild-type mice. Cd1d-/- mice also had increased neuronal injury, neurological dysfunction, and worse mortality after CA. To therapeutically enhance dNKT cell activity, we treated mice with sulfatide lipid after CA, showing that it improved neurological function. Together, these data show that sulfatide-specific dNKT cells are associated with good neurological outcomes after clinical OHCA and are neuroprotective in mice after CA. Strategies to enhance the number or function of dNKT cells may thus represent a treatment approach for CA.

Diagnostic Accuracy of Treponema pallidum Immunostaining in a Cohort of Patients With Secondary Syphilis.

Diagnostic Accuracy of Treponema pallidum Immunostaining in a Cohort of Patients With Secondary Syphilis.

Etiology and therapy of pharyngeal perforations.

The primary aim of this study is to evaluate the impact of diagnostic procedures and treatment interventions performed at our medical institution on the final outcomes and survival rates of patients with iatrogenic and traumatic pharyngeal perforation (PP). We reviewed the medical records of 36 patients with iatrogenic and trauma-induced PP who were treated at the Quaternary Medical Center of Otorhinolaryngology between 2010 and 2020. Comorbidities were classified according to the Age-adjusted Charlson Comorbidity Index (ACCI) scoring system, and postoperative complications were classified according to the Clavien and Dindo scoring system. Of the 36 patients, 15 (41.7%) were male and 21 (58.3%) were female. The median age was 73 years, and PP was typically diagnosed within one day. Notably, the perforation site was identified in the hypopharynx in 29 (80.5%) patients. The median ACCI score was 4, with the most frequent ACCI score observed being 5. During the treatment course, 17 patients (47.2%) experienced complications, with 9 of these patients experiencing grade IV complications according to the Clavien and Dindo classification. Our study showed that patients with hypopharyngeal perforations have an almost 42-fold higher risk of mortality during hospitalization compared to those with epipharyngeal or oropharyngeal perforations, though results are limited by the small sample size and the variable dates. Additionally, neurosurgery of the cervical spine, transesophageal echocardiography, and diverticular surgery emerged as procedures carrying the highest risk for pharyngeal perforations. Within our patient cohort, 4 patients (11.11%, all female) died during the treatment course.

Impact of ustekinumab exposure on clinical outcomes during induction in inflammatory bowel disease.

Understanding the relationship between ustekinumab (UST) exposure and clinical outcomes in inflammatory bowel disease (IBD) induction is crucial. However, evidence remains limited, highlighting the need to comprehend UST's pharmacokinetic variability for tailored treatments. This study aimed to investigate the association between UST exposure during the induction phase and clinical outcomes and identifying factors associated with UST exposure during this period. A retrospective observational study was conducted on a cohort of consecutive IBD patients. The primary endpoint was to assess the association between UST exposure at week 8 and both clinical and biochemical remission at week 26, as well as the absence of disease flare-ups during the initial six months of treatment. The secondary endpoint was to investigate the relationship between baseline characteristics and UST exposure at week 8. A total of 56 IBD patients were included. Variables associated with adequate UST exposure included baseline fecal calprotectin < 500 µg/g (OR: 7.72 [95% CI: 1.75-34.03]) and female sex (OR: 4.56 [95% CI: 1.12-18.60]). A cut-off UST trough leveles of 8.3 μg/mL yielded an area under the curve (AUC) of 0.74 (95% CI: 0.58-0.90, p=0.021) to predict normal fecal calprotectin levels, and 8.6 µg/ml resulted in an AUC of 0.724 (95% CI: 0.558-0.863) to predict clinical remission. This study demonstrates a significant association between UST concentrations and clinical and biochemical remission in IBD patients. Results suggest that standard induction doses may not be sufficient for all patients, highlighting the importance of treatment individualization to optimize outcomes.

Overview of acomparative analysis of microsatellite instability and standard mismatch repair protein-deficiency tests in alarge cancer cohort.

Mismatch repair deficiency (dMMR) with microsatellite instability (MSI) is frequent in cancer, particularly in gastrointestinal and endometrial malignancies. The increased tumor mutational burden renders dMMR/MSI tumors suitable targets for immune checkpoint inhibitors-provided the regulatory genetic defect can be detected. dMMR and MSI are considered equally effective predictors of the efficacy of ICIs; however, while dMMR testing is based on detection of missing MMR proteins in immunohistochemistry (IHC), MSI polymerase chain reaction (PCR) testing focuses on the consequences of dMMR at the genomic level. Aretrospective analysis was carried out in alarge cancer cohort (n = 1306). dMMR was tested by four IHC reactions (MLH1, PMS2, MSH2, MSH6), and MSI was assessed by pentaplex PCR (BAT-25, BAT-26, MONO-27, NR-21, NR-24) in 703cases. In 64cases (5%), technical failures (mostly poor preanalytical fixation) prevented dMMR/MSI testing. Tumors were colorectal (CRC; n: 978), cancer of unknown primary (n: 126), endometrial (n: 39), pancreatic (n: 36), and gastric (n: 33). dMMR was diagnosed as classical, nonclassical, or unusual, depending on IHC. The MSI-high incidence was 12.1% overall and similar in the CRC subcohort. Interestingly, the dMMR incidence was higher in the total cohort (20.3%) and similar in the CRC subcohort. The incidences of proficient MMR (pMMR) and microsatellite stability (MSS) were similar in the total cohort and in the CRC subcohort. A19.3% discrepancy was found between MMR IHC and MSI PCR for the entire cohort, independent of tumor types. In the case of pMMR, the discrepancy rate for MSS/MSI-low was low (2.0%; entire cohort and the CRC subcohort). However, the discrepancy between dMMR and MSI-high was high within the entire cohort (60.9%) and in the CRC (58.6%) and non-CRC subcohorts (68%). This high discrepancy was not due to tumors with alow T/N ratio. Regarding dMMR phenotypes, classical dMMR had a~ 60% correlation with MSI-high status, while non-classical dMMR had amuch lower and unusual dMMR avery low (< 10%) correlation with MSI-high in the entire cohort and in the CRC subcohort. Overall, the MSI PCR sensitivity for MMR IHC status was very low. dMMR and MSI-high likely result in an increased rate of structurally altered proteins, i.e., neoantigens, and the efficacy of cancer immunotherapies is thus expected to be higher. We compared MMR IHC to MSI PCR in alarge cohort of cancer patients to study how PCR test results correlate to MMR IHC. Our data imply that preanalytical factors strongly influence the results of MMR IHC and MSI PCR and may question the current dogma that dMMR phenotype and genetic MSI status are equivalent predictive markers for immunotherapies.

Lung function in adult patients with osteogenesis imperfecta: a cohort study

BackgroundOsteogenesis imperfecta (OI) is a rare hereditary bone disease resulting from a defect in collagen synthesis or processing, leading to bone fragility, frequent fractures and skeletal deformities. OI is associated with increased respiratory morbidity and mortality, but the mechanisms of lung involvement are poorly understood, and there are no data on the natural history of lung function. We studied lung function over time in a cohort of adult OI patients at one center.MethodsWe used data from OI patients aged 15 and above followed up at the Lausanne university hospital between 2012 and 2023 with available pre-bronchodilator spirometry. Associations between spirometric measurements at first visit and clinical characteristics were studied through linear regression. Changes of spirometric variables over time were analysed through mixed linear regression. Models were adjusted for age, sex, height and OI type (Sillence classification).ResultsAmong 46 subjects, 24% had impaired spirometry at baseline, with similar distribution between restrictive (8.7%), obstructive (8.7%) and mixed (6.5%) ventilatory patterns. At first visit, higher age was associated with lower FEV1 (β = −0.019 l, p = 0.014) and lower FEV1/FVC (β = −0.175%, p = 0.012). A history of asthma was associated with higher FEV1 (β = 0.636 l, p = 0.028) and FVC (β = 0.834 l, p = 0.010). At first visit, FEV1 (β = −0.750 l, p = 0.006) and FVC (β = −0.859 l, p = 0.004) was lower in individuals with OI Sillence types 3, 4 or 5 compared to type 1. Over a mean follow-up of 3.4 years, smokers had a greater decline of FEV1/FVC compared to non-smokers (β = −6.592%, p = 0.007). Individuals with a mutation in the gene COL1A2 had 740 ml lower FVC compared to those with a mutation in COL1A1 (p = 0.037). After adjustment for sex, age, height and OI type, FEV1 increased by 26 ml (95% CI 8; 45) or 1.28%pred (0.51; 2.05) and FVC increased by 25 ml (95% CI 8; 43) or 0.93%pred (0.31; 1.55) per year of follow-up.ConclusionsAn increase of FEV1 and FVC over time was observed in OI patients after adjustment for other variables, suggesting that the defective collagen synthesis may impact the pulmonary interstitium and lead to increased lung compliance and hyperinflation, in contrast to skeletal deformities, which reduce the thoracic volume. Lung function changes in OI thus result from the interplay of several mechanisms.

Leucencephalopathy in Patients with Parkinson's Disease and Deep Brain Stimulation.

Leucencephalopathy (LE) is often detected on magnetic resonance imaging in elderly patients. These white matter lesions may interfere with lead trajectories for deep brain stimulation (DBS) in patients with Parkinson's disease (PD) and are associated with complications after DBS surgery. This study was conducted to assess the incidence of LE in PD patients and to evaluate correlations with complications after DBS surgery. A consecutive cohort of PD patients who underwent DBS surgery in the subthalamic nucleus (STN-DBS) was retrospectively analyzed. The presence and extent of LE were quantified using the Fazekas scale. Postoperative complications were extracted from the medical records. DBS efficacy was calculated using the side-specific motor symptom ratio (Unified Parkinson's Disease Rating Scale, Part III, postoperative stimulation ON/medication off divided by preoperative medication off) at 1-year follow-up. A total of 135 PD patients were included in the study. LE was detected in 35.6% (48/135) of the patients. In 87.7% (57/65), LE was mild, in 10.7% (7/65) moderate, and in 1.6% (1/65) severe. A higher incidence of mild to moderate LE did not correlate with postoperative hemorrhage or postoperative infection. There was no correlation of LE with stimulation efficacy (r = -0.05, P = 0.69) or with surgical index (r = -0.10, P = 0.35). Neither was the presence of mild to moderate LE associated with an increased risk for surgical complications, nor did it negatively impact the long-term improvement in motor function after DBS surgery in PD patients. Therefore, mild to moderate LE should not be considered a contraindication for DBS.

Adenocarcinoma of the rete testis: clinicopathological study of 18 cases with emphasis on MET amplification and a review of the literature.

Knowledge regarding adenocarcinoma of the rete testis (ACRT) is extremely limited due to its scarcity. This study enrolled 18 patients with ACRT from multiple institutions. Clinicopathological and immunohistochemical features were investigated, together with a comprehensive review of 95 previously reported cases. One case was assessed using next-generation sequencing (NGS). The median age of the patient cohort was 54 years (range = 20-69 years), with the majority presenting with a testicular mass (13 of 18); predominantly right-sided (11 of 18). Six patients died within the second year following diagnosis. The morphology of ACRT spans a wide spectrum, including newly identified mucinous carcinoid-like features, with mucous cells floating in mucus and signet-ring cells. Notably, transition from a benign to a malignant rete epithelium was noted in 38.9% of cases (seven of 18). Immunohistochemically, tumour cells most frequently showed strong positivity for CK7 (12 of 16) and CK20 (10 of 17), with occasionally positivity for calretinin (three of 16), WT-1 (two of 17) and PAX-8 (two of 15). According to NGS in a single case, MET was amplified, leading to the patient benefiting from mesenchymal-epidermal transition factor (MET) inhibitors. Furthermore, MET amplification was assessed in 13 cases using fluorescence in-situ hybridisation and detected in two cases (15.4%). No significant correlation between MET amplification and mesenchymal-epidermal transition factor (MET) levels was observed in the cases studied. Primary ACRT is a rare malignant tumour which poses a diagnostic challenge, and is associated with poor prognosis. Cases of ACRT with MET amplification might represent promising candidates for the treatment with MET inhibitors.

Exploring the Role of CCNF Variants in Italian ALS Patients

Objectives: Variants in Cyclin F (CCNF) have been associated to amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) in a group of cases. The objectives of this study were to determine the contribution of CCNF in a large cohort of Italian ALS patients, to look for genotype-phenotype correlation of the mutations and to evaluate the CCNF-associated clinical features. Methods: We applied next-generation sequencing technologies on 971 unrelated Italian ALS patients and we filtered results to look for variants in CCNF gene. Results: We identified 13 rare missense variants in 16 index cases (2 familial and 14 sporadic), with a cumulative mutational frequency of 1.6%. The most prevalent variant was p.Phe197Leu, found in three patients. The clinical presentation was heterogeneous, with a classic phenotype in eight patients, upper motor neuron dominant (UMN-D) phenotype in four patients, and flail arm in four patients. Clinical evaluation for cognitive impairment was performed in 13 patients using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) test, demonstrating that almost half of the patients (n = 6) had variable degrees of frontal dysfunction. Discussion: In our cohort, we observed CCNF variants in 1.6% of patients (16/971), a percentage similar to that found in other series. Clinical presentation is heterogeneous, but CCNF variants are significantly associated to cognitive impairment. Conclusions: Our study expands the CCNF genetic variant spectrum in a large cohort of Italian ALS patients. Further studies are needed to assess genotype-phenotype associations of CCNF variants and to specify the role of each variant, which are quite common, especially in sALS patients.

Differential predictive value of resident memory CD8+T cell subpopulations in patients with non-small-cell lung cancer treated by immunotherapy

BackgroundA high density of resident memory T cells (TRM) in tumors correlates with improved clinical outcomes in immunotherapy-treated patients. In most clinical studies, TRM are defined by the CD103 marker....

Impact of anemia on renal outcomes in elderly patients with chronic kidney disease: a cohort study

BackgroundWe aimed to examine the impact of anemia on the risk of further deterioration in renal function among elderly and nonelderly patients with chronic kidney disease (CKD).MethodsIn this retrospective cohort study, we included 1098 predialysis patients with CKD hospitalized for an educational program on CKD between January 2010 and December 2018. Patients aged < 75 years (657) were considered nonelderly, and those aged ≥ 75 years (441) were considered elderly; each category was stratified by hemoglobin level to evaluate the incidence of CKD progression: < 9.0 g/dL, 9.0–10.9 g/dL, 11.0–12.9 g/dL, and ≥ 13.0 g/dL. The study was terminated after 3 years of observation.ResultsCKD progression occurred in 550 and 304 patients in the nonelderly and elderly group, respectively. In the nonelderly group, multivariate Cox models revealed that an increased risk of CKD progression was observed in patients with low hemoglobin levels compared with those with hemoglobin levels of 11.0–12.9 g/dL. However, in the elderly group, adverse renal outcomes occurred at rates that did not differ significantly according to the hemoglobin level. Furthermore, we isolated patients with hemoglobin levels of 9.0–10.9 g/dL and 11.0–12.9 g/dL and analyzed the risk of renal outcomes in both nonelderly and elderly people among them. Examination of renal outcomes in 1:1 the propensity-score-matched cohort of patients with hemoglobin levels of 9.0–10.9 g/dL versus patients with levels of 11.0–12.9 g/dL yielded consistent results.ConclusionsMild anemia may be poorly associated with renal prognosis in elderly patients with CKD.

Efficacy and safety of combining anti-angiogenic therapy, radiotherapy, and PD-1 inhibitors in patients with driver gene-negative non-small cell lung cancer brain metastases: a retrospective study

BackgroundThe efficacy and safety of anti-angiogenic combination therapy in patients with driver gene-negative non-small cell lung cancer (NSCLC) with brain metastases (BM) are uncertain.MethodsEighty-eight records of driver gene-negative patients with NSCLC treated with craniocerebral radiotherapy (RT) and programmed death factor-1 (PD-1) inhibitors between May 2021 and May 2023 were collected. Based on whether anti-angiogenic therapy (AT) is combined or not, patients are categorized into the AT group and the non anti-angiogenic therapy (NAT) group. The NAT group patients received craniocerebral RT and PD-1 inhibitor and those in the AT group received craniocerebral RT and PD-1 inhibitor with ≥ 4 cycles of AT. Comparing the clinical efficacy and safety in these two patient cohorts was the main goal of the study.ResultsBy May 1, 2024, the iORR was 94.0% and 63.2% for AT and NAT group, respectively. The 1- and 2-year iLPFS for AT and NAT group were 93.6%, 80.9% and 69.7%, 36.4%, respectively. The 1- and 2-year iDPFS were 86.7%, 56.3% and 59.1%, 48.3%, respectively. The 1- and 2-year OS were 82.0%, 36.6% and 68.4%, 34.6%, respectively. Compared to the standard treatment (RT and PD-1 inhibitors), the addition of AT prolonged the median iLPFS (NR vs. 22.0 months, hazard ratio [HR] = 11.004, P < 0.001) and the median iDPFS (NR vs. 20.0 months, HR = 8.732, P = 0.003), but was not significant in the extension of the OS (21.0 vs. 19.0 months, HR = 1.601, P = 0.206). Multivariable analysis showed that combination therapy with AT is significantly associated with prolonged iLPFS (HR = 4.233, P = 0.002) and iDPFS (HR = 2.824, P = 0.007), whereas only GPA score is significantly associated with improved OS (HR = 0.589, P = 0.019). The incidence of hypertension in the AT group showed an increasing trend, and no significant increased risk of radiation-induced brain necrosis was found. No drug-related intracranial hemorrhage events occurred.ConclusionCombining AT, RT, and PD-1 inhibitors can substantially improve iLPFS and iDPFS for patients with driver gene-negative NSCLC with BM; however, it is not significantly associated with better OS.