Treatment of Schatzker Type VI Tibia Fractures Using Circular External Fixation: State of the Art, Surgical Technique and Results.

BACKGROUND: Schatzker type VI tibia fractures are usually associated with infection and surgical wound-related problems. Circular external fixation (CEF) has been shown to minimize such complications. METHODS: We pose a retrospective study of patients with Schatzker type VI fractures treated with CEF. RESULTS: Twenty-two (22) patients were included (11M/11F) with a mean age of 60.1 ± 14.9 years. According to the AO/OTA classification, two fractures (9.1%) were A2, three (13.6%) were A3, and seventeen (77.3%) were C3. Three (13.6%) of them were open. The tissue damage observed in the nineteen (86.4%) closed fractures was classified according to Tscherne (four grade I, twelve grade II, and three grade III). The mean ex-fix time was 24.1 ± 5.1 weeks. None of the patients experienced deep infections, nonunion, or malunion. The mean ROM was 111.4 ± 17.8 degrees. Although stability was achieved in all cases, 50% of them suffered osteoarthritic degeneration. Four knees required TKR at a mean of 8.77 ± 5.58 years from trauma. The mean HHS knee score was 84.2 ± 10.3 points (excellent in fifteen (68.2%) cases, good in four (18.2%), and acceptable in three (13.6%)). The mean Rasmussen radiological score was 13.3 ± 3.5 (excellent in three (13.6%) cases, good in fifteen (68.2%), and acceptable in four (18.2%)). The mean SF-12 score was 35.1 ± 10.4 points on the physical scale and 53.0 ± 10.6 points on the mental scale. CONCLUSIONS: CEF has shown itself to be a valid treatment for patients with Schatzker type VI fractures, particularly for those where the fracture is comminuted, severely displaced, open, or associated with severe soft tissue damage.

Occipital-interhemispheric transtentorial pineal mass resection.

The occipital approach for pineal tumors was first described by James Poppen in 1966. Since then, it has been widely used for accessing deep-seated tumors as it offers a wider surgical view than the supracerebellar transtentorial approach. This video demonstrates the technical nuances of the occipital transtentorial approach and the exoscopic dissection of a pineal gland tumor in a 66-year-old male. Use of the exoscope over the microscope provides certain ergonomic advantages and improves surgical workflow, as demonstrated here. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23161.

Frontotemporal craniotomy with orbital osteotomy for superior hypophyseal artery aneurysm clipping.

Superior hypophyseal artery (SHA) aneurysms are rare paraclinoid aneurysms with a mortality rate as high as 3%-6%. Surgical clipping of these aneurysms is technically challenging due to the surrounding anatomy. The large size and complicated surrounding anatomy make endovascular coiling very difficult. Here we present the case of a ruptured right SHA aneurysm. The authors present technical nuances of the clipping using an exoscope rather than a traditional microscope. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23157.

Incidence, and factors associated with moderate/severe pediatric traumatic brain injury in children aged 5-15 years in western, Mexico.

OBJECTIVE: The study objectives were to estimate the standardized incidence and evaluate factors associated with moderate/severe pediatric traumatic brain injury (p-TBI) in children aged 5-15 years in Western, Mexico. METHODS: The study was cross-sectional in design. We estimated the standardized incidence of moderate/severe p-TBI using the direct methods of the World Health Organization (WHO) standard populations. We utilized the Glasgow Coma Scale (GCS) to identify moderate/severe p-TBI patients (GCS ≤ 13). Logistic regression analysis was applied to evaluate variables associated with moderate/severe p-TBI. RESULTS: The standardized incidence of patients diagnosed with moderate/severe p-TBI was 31.0/100,000 person-years (95 % CI 28.7-33.4). According to age, the moderate/severe TBI group was included. A total of 254 (38.5 %) patients were aged 5-9 years, 343 (52.0 %) were aged 10-14 years, and 62 (9.5 %) were aged 15 years. Factors associated with moderate/severe TBI in the crude analysis were male sex (OR 5.50, 95 % CI 4.16-7.39, p < 0.001), primary school (OR 2.15, 95 % CI 1.62-2.84, p < 0.001), and falls (OR 1.34, 95 % CI 1.02-1.77, p = 0.035). Factors associated with moderate/severe p-TBI in the adjusted analysis were male sex (OR 6.12, 95 % CI 4.53-8.29, p < 0.001), primary school (OR 3.25, 95 % CI 2.31-4.55, p < 0.001), and falls (OR 1.78, 95 % CI 1.28-2.47, p < 0.001). CONCLUSION: The incidence of moderate/severe p-TBI in children aged 5-15 years in western Mexico in this study was higher than that in other studies. One of the biggest factors associated with moderate/severe p-TBI was male sex, specifically those with lower education levels and those who were prone to falls.

Stroke in Tuberculous Meningitis.

A 17-year-old male presented with a 20-day history of vomiting, abdominal pain, weight loss, headache and fever progressing to dysarthria, somnolence, urinary incontinence, slurred speech, weakness, and inability to walk. Neurological examination revealed diminished visual acuity and diplopia. A head computed tomography (CT) showed acute hydrocephalus (Figure 1). Cerebrospinal fluid (CSF) analysis revealed pleocytosis (lymphocyte predominant), hypoglycorrhachia (8 mg/dL), and hyperproteinorrachia (156 mg/dL). The brain magnetic resonance imaging (MRI) revealed leptomeningitis, basal ganglia infarcts and basal meningeal enhancement highly suggestive of tuberculous meningitis (TBM) (Figure 2). We calculated a positive Thwaites score (-5) for TBM. The patient responded well to antituberculous treatment and dexamethasone. At 2 year follow-up the patient remains symptom-free. Stroke is a frequent complication of TBM and might contribute to long-term disability. Brain imaging findings, such as basal meningeal enhancement and basal exudates, hydrocephalus, and infarctions (TBM triad) are useful tools to rapidly identify probable TBM(3,4). Brain infarcts in TBM are located mostly in the arterial territory of distal branching arterires(5). Other less frequent imaging findings are tuberculomas and vasospasm. Key message: Hydrocephalus, basal meningeal enhancement, and basal ganglia infarcts should raise suspicion of tuberculosis, especially in endemic regions.

Cerebral Venous Thrombosis Presenting as Simultaneous Intracerebral Hemorrhage.

A 37-year-old pregnant woman presented to the emergency department with central facial palsy, ipsilateral right hemiparesis, and seizures. Brain Computed Tomogram (CT) showed intracerebral hemorrhage (ICH) and bilateral frontal edema. Magnetic resonance imaging (MRI) revealed multifocal hemorrhages consistent with a diagnosis of multiple simultaneous ICH (MSICH) (Figure 1). We suspected cerebral venous thrombosis (CVT) and performed a MR angiogram confirming this diagnosis (Figure 2). Upon admission, the patient was treated with low-molecular-weight heparin and transitioned to direct oral anticoagulation at discharge. Non traumatic MSICH is a rare imaging finding with high mortality, usually arterial in origin (1). However, since treatment options vary, cerebral venous thrombosis should always be considered in the differential diagnosis, especially in young female patients with known risk factors, such as pregnancy and puerperium (2-4). MRI modalities (Echo-GRE) are valuable tools in identifying ICH when CT is inconclusive (5).

Características epidemiológicas y quirúrgicas en pacientes con secuelas de enfermedad de Fournier / Reconstructive techniques in Fournier's disease sequels

Introducción: La gangrena de Fournier actualmente se define como una forma específica de fascitis necrotizante sinérgica, rápida, progresiva y de origen multibacteriano, que afecta principalmente la fascia muscular de región perineal, genital o perianal e incluso de pared abdominal; con punto de partida genitourinario, colorrectal o idiopático. Todo ello, acompañado de gangrena de piel de estas áreas debida a trombosis de vasos sanguíneos subcutáneos. Objetivos: Describir las características epidemiológicas y quirúrgicas de los pacientes secuelares de la enfermedad de Fournier en la Unidad de Cirugía Plástica del Hospital de Clínicas en un período de 2 años. Materiales y métodos: Estudio observacional, descriptivo, de corte transversal, temporalmente retrospectivo, tipo serie de casos. El tipo de muestreo fue no probabilístico a conveniencia. Se presentan 18 pacientes secuelares de enfermedad de Fournier reconstruidos en la Unidad de Cirugía Plástica de Hospital de Clínicas entre los años 2020 y 2021. Resultados: Durante el periodo del estudio se realizaron 395 cirugías en el Servicio de Cirugía Plástica del Hospital de Clínicas, de los cuales 18 pacientes fueron intervenidos quirúrgicamente por secuelas de enfermedad de Fournier, lo que representa el 5% del total. En lo que respecta a las variables demográficas, la edad osciló entre los 37 y 85 años con mayor afectación en la sexta década de la vida con un promedio de 61 años. El 94% de los pacientes fue de sexo masculino; el 89% de los pacientes tenía como patología de base la diabetes mellitus tipo 2, seguido de la obesidad en el 72% y la hipertensión arterial en el 56% de los casos; el 83% de los casos estuvo afectada la región escrotal seguido de la región perineal con el 56% de los pacientes y el pene en el 50% de los casos. La técnica reconstructiva empleada en mayor frecuencia fueron los colgajos en 10 pacientes, seguido del injerto de piel en 8 pacientes, y el cierre primario en 6 pacientes, cabe mencionar que en algunos pacientes se emplearon varias técnicas reconstructivas siguiendo el concepto de reconstrucción por sub-unidades anatómicas, entre los colgajos los más utilizados fueron el colgajo de perforante de la circunfleja femoral medial (perforante de gracilis) con el 50% de los casos seguido del colgajo de transposición fasciocutáneo de la pudenda interna con el 30%, y por último el colgajo de avance fasciocutáneo con el 20% (Tabla 3). La estancia hospitalaria promedio fue de 3 días, con un mínimo de 1 día y un máximo de 5 días post operatorio. Se reportó como complicación la dehiscencia de sutura en 3 pacientes, no se observó complicaciones en el 77% de los casos. Conclusión: Las secuelas de la enfermedad de Fournier sometidos a cirugías representan el 5% del total de cirugías realizadas en nuestro Servicio, son más prevalentes en la sexta década de la vida, afecta más al sexo masculino con diabetes mellitus tipo 2 como patología de base, las técnicas reconstructivas empleadas en las secuelas son variables de acuerdo a las regiones anatómicas afectadas y pueden abarcar desde el cierre primario hasta la utilización de colgajos para su reparación.

Introduction: Fournier's gangrene is currently defined as a specific form of synergistic, rapid, progressive and multibacterial necrotizing fasciitis, which mainly affects the muscular fascia of the perineal, genital, or perianal region and even the abdominal wall; with genitourinary, colorectal, or idiopathic starting point. All of this, accompanied by skin gangrene in these areas due to thrombosis of subcutaneous blood vessels. Objectives: To describe the epidemiological and surgical characteristics of the sequelae patients of Fournier's disease in the Plastic Surgery Unit of the Hospital de Clínicas in a period of 2 years. Materials and methods: Observational, descriptive, cross-sectional, temporally retrospective, case series type study. The type of sampling was non-probabilistic at convenience. Eighteen sequelae patients of Fournier's disease reconstructed in the Plastic Surgery Unit of Hospital de Clínicas between 2020 and 2021 are presented. Results: During the study period, 395 surgeries were performed in the Plastic Surgery Service of the Hospital de Clínicas, of which 18 patients underwent surgery for sequelae of Fournier's disease, which represents 5% of the total. Regarding demographic variables, age ranged between 37 and 85 years with greater impact in the sixth decade of life with an average of 61 years. 94% of the patients were male; 89% of the patients had type 2 diabetes mellitus as an underlying pathology, followed by obesity in 72% and high blood pressure in 56% of cases; In 83% of the cases, the scrotal region was affected, followed by the perineal region in 56% of the patients and the penis in 50% of the cases. The most frequently used reconstructive technique was flaps in 10 patients, followed by skin grafting in 8 patients, and primary closure in 6 patients. It is worth mentioning that in some patients several reconstructive techniques were used following the concept of reconstruction by sub- anatomical units, among the flaps the most used were the medial femoral circumflex perforator flap (gracilis perforator) with 50% of the cases followed by the fasciocutaneous transposition flap of the internal pudendal with 30%, and finally the fasciocutaneous advancement flap with 20% (Table 3). The average hospital stay was 3 days, with a minimum of 1 day and a maximum of 5 days postoperatively. Suture dehiscence was reported as a complication in 3 patients; no complications were observed in 77% of the cases. Conclusion: The sequelae of Fournier's disease undergoing surgeries represent 5% of the total number of surgeries performed in our Service, they are more prevalent in the sixth decade of life, it affects more males with type 2 diabetes mellitus as the underlying pathology, the reconstructive techniques used in the sequelae are variable according to the anatomical regions affected and can range from primary closure to the use of flaps for repair.

A Rare Giant Nasofrontal Meningoencephalocele with Nasal and Visual Obstruction.

The encephalocele is a malformation that is manifested by the protrusion of brain tissue through a defect in the skull. The meningoencephalocele contains the meninges and brain tissue. Frontoethmoidal or nasal meningoencephalocele is rare; the frequency is approximately one in 40,000 live births. Three subtypes are currently known: nasoethmoid, nasofrontal, and nasoorbital. The authors report the clinical case of a 2-month-old girl with a very rare giant nasofrontal meningoencephalocele, which affected vision and breathing. The patient underwent surgery at an early age to avoid significant functional sequelae and promote the normal development and growth of the girl.

Novel targets for immune-checkpoint inhibition in cancer.

Immune-checkpoint inhibitors have revolutionized cancer therapy, yet many patients either do not derive any benefit from treatment or develop a resistance to checkpoint inhibitors. Intrinsic resistance can result from neoantigen depletion, defective antigen presentation, PD-L1 downregulation, immune-checkpoint ligand upregulation, immunosuppression, and tumor cell phenotypic changes. On the other hand, extrinsic resistance involves acquired upregulation of inhibitory immune-checkpoints, leading to T-cell exhaustion. Current data suggest that PD-1, CTLA-4, and LAG-3 upregulation limits the efficacy of single-agent immune-checkpoint inhibitors. Ongoing clinical trials are investigating novel immune-checkpoint targets to avoid or overcome resistance. This review provides an in-depth analysis of the evolving landscape of potentially targetable immune-checkpoints in cancer. We highlight their biology, emphasizing the current understanding of resistance mechanisms and focusing on promising strategies that are under investigation. We also summarize current results and ongoing clinical trials in this crucial field that could once again revolutionize outcomes for cancer patients.

Neoadjuvant Immunotherapy: A Promising New Standard of Care.

Neoadjuvant immunotherapy has emerged as a promising approach in the treatment of various malignancies, with preclinical studies showing improved immune responses in the preoperative setting. FDA-approved neoadjuvant-immunotherapy-based approaches include triple-negative breast cancer and early non-small cell lung cancer on the basis of improvement in pathological response and event free survival. Nevertheless, current trials have only shown benefits in a fraction of patients. It is therefore crucial to identify predictive biomarkers to improve patient selection for such approaches. This review aims to provide an overview of potential biomarkers of neoadjuvant immunotherapy in early triple-negative breast cancer, bladder cancer, melanoma, non-small cell lung cancer, colorectal cancer and gastric cancer. By the extrapolation of the metastatic setting, we explore known predictive biomarkers, i.e., PD-L1, mismatch repair deficiency and tumour mutational burden, as well as potential early-disease-specific biomarkers. We also discuss the challenges of identifying reliable biomarkers and the need for standardized protocols and guidelines for their validation and clinical implementation.

Genetic portrait of the Amazonian communities of Peru and Bolivia: The legacy of the Takanan-speaking people.

During the colonial period in South America, many autochthonous populations were affected by relocation by European missionary reductions and other factors that impacted and reconfigured their genetic makeup. Presently, the descendants of some "reduced" and other isolated groups are distributed in the Amazonian areas of Peru, Bolivia, and Brazil, and among them, speakers of Takanan and Panoan languages. Based on linguistics, these peoples should be closely related, but so far no DNA comparison studies have been conducted to corroborate a genetic relationship. To clarify these questions, we used a set of 15 short tandem repeats of the non-recombining part of the Y-chromosome (Y-STRs) and mitochondrial DNA (mtDNA) control region sequence data. Paternal line comparisons showed the Takanan-speaking peoples from Peru and Bolivia descended from recent common ancestors; one group was related to Arawakan, Jivaroan, and Cocama and the other to Panoan speakers, consistent with linguistics. Also, a genetic affinity for maternal lines was observed between some Takanan speakers and individuals who spoke different Amazonian languages. Our results supported a shared ancestry of Takanan, Panoan, Cocama, and Jivaroan-speaking communities who appeared to be related to each other and came likely from an early Arawak expansion in the western Amazonia of South America.

Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study.

BACKGROUND: Carriers of germline pathogenic variants of the BRCA1 gene (gBRCA1) tend to have a higher incidence of haematological toxicity upon exposure to chemotherapy. We hypothesised that the occurrence of agranulocytosis during the first cycle of (neo-)adjuvant chemotherapy (C1) in breast cancer (BC) patients could predict gBRCA1 pathogenic variants. PATIENTS AND METHODS: The study population included non-metastatic BC patients selected for genetic counselling at Hôpitaux Universitaires de Genève (Jan. 1998 to Dec. 2017) with available mid-cycle blood counts performed during C1. The BOADICEA and Manchester scoring system risk-prediction models were applied. The primary outcome was the predicted likelihood of harbouring gBRCA1 pathogenic variants among patients presenting agranulocytosis during C1. RESULTS: Three hundred seven BC patients were included: 32 (10.4%) gBRCA1, 27 (8.8%) gBRCA2, and 248 (81.1%) non-heterozygotes. Mean age at diagnosis was 40 years. Compared with non-heterozygotes, gBRCA1 heterozygotes more frequently had grade 3 BC (78.1%; p = 0.014), triple-negative subtype (68.8%; p <0.001), bilateral BC (25%; p = 0.004), and agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy (45.8%; p = 0.002). Agranulocytosis and febrile neutropenia that developed following the first cycle of chemotherapy were independently predictive for gBRCA1 pathogenic variants (odds ratio: 6.1; p = 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value for agranulocytosis predicting gBRCA1 were 45.8% (25.6-67.2%), 82.8% (77.5-87.3%), 22.9% (6.1-37.3%), and 93.4% (88.9-96.4%), respectively. Agranulocytosis substantially improved the positive predictive value of the risk-prediction models used for gBRCA1 evaluation. CONCLUSION: Agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy is an independent predictive factor for gBRCA1 detection in non-metastatic BC patients.

Hematologic toxicities of chemotherapy in breast and ovarian cancer patients carrying BRCA1/BRCA2 germline pathogenic variants. A single center experience and review of the literature.

BRCA1 and BRCA2 play a central role in DNA repair and their germline pathogenic variants (gBRCA) confer a high risk for developing breast and ovarian cancer. Standard chemotherapy regimens for these cancers include DNA-damaging agents. We hypothesized that gBRCA carriers might be at higher risk of developing chemotherapy-related hematologic toxicity and therapy-related myeloid neoplasms (t-MN). We conducted a retrospective study of women newly diagnosed with invasive breast or ovarian cancer who were screened for gBRCA1/gBRCA2 at Geneva University Hospitals. All patients were treated with (neo-)adjuvant chemotherapy. We evaluated acute hematologic toxicities by analyzing the occurrence of febrile neutropenia and severe neutropenia (grade 4) at day 7-14 of the first cycle of chemotherapy and G-CSF use during the entire chemotherapy regimen. Characteristics of t-MN were collected. We reviewed medical records from 447 patients: 58 gBRCA1 and 40 gBRCA2 carriers and 349 non-carriers. gBRCA1 carriers were at higher risk of developing severe neutropenia (32% vs. 14.5%, p = 0.007; OR = 3.3, 95% CI [1.6-7], p = 0.001) and of requiring G-CSF for secondary prophylaxis (58.3% vs. 38.2%, p = 0.011; OR = 2.5, 95% CI [1.4-4.8], p = 0.004). gBRCA2 carriers did not show increased acute hematologic toxicities. t-MN were observed in 2 patients (1 gBRCA1 and one non-carrier). Our results suggested an increased acute hematologic toxicity upon exposure to chemotherapy for breast and ovarian cancer among gBRCA1 but not gBRCA2 carriers. A deeper characterization of t-MN is warranted with the recent development of PARP inhibitors in frontline therapy in gBRCA breast and ovarian cancer.

Evolution of biological features of invasive lobular breast cancer: Comparison between primary tumour and metastases.

BACKGROUND: Invasive lobular carcinoma (ILC) has unique clinical-biological features. Phenotypical differences between primary tumours (PTs) and metastases (M) have been described for invasive ductal carcinoma, but data on ILC are limited. METHODS: We retrospectively analysed patients with recurrent ILC from our institution from 2013 to 2020. We evaluated the discordance of the oestrogen receptor (ER), progesterone receptor (PgR) and HER2 between PT and M, to understand prognostic and therapeutic implications. RESULTS: Thirteen percent (n = 91) of all patients had ILC. We observed 15%, 44% and 5% of ER, PgR and HER2 status discordance between PT and M. ER/PgR discordance was related to receptor loss and HER2 mainly due to gain. PT presented a luminal-like phenotype (93%); 6% and 1% were triple-negative (TNBC) and HER2-positive. In M, there was an increase in TNBC (16%) and HER2-positive (5%). Metastasis-free survival and overall survival (OS) were different according to clinical phenotype, with poorer prognosis for HER2+ and TNBC (p < 0.001); OS after metastatic progression did not differ across phenotypes (p = 0.079). In luminal-like ILC (n = 85) at diagnosis, we found that OS after relapse was poorer in patients experiencing a phenotype switch to TNBC but improved in patients with HER2 gain (p = 0.0028). Poorer survival was reported in patients with a PgR and/or ER expression loss of ≥25%. There was HER2-low enrichment in M1 (from 37% to 58%): this change was not associated with OS (p > 0.05). CONCLUSION: Our results suggest that phenotype switch after metastatic progression may be associated with patients' outcomes. Tumour biopsy in recurrent ILC could drive treatment decision-making, with prognostic implications.

Metabolic Adjustments following Glutaminase Inhibition by CB-839 in Glioblastoma Cell Lines.

Most tumor cells can use glutamine (Gln) for energy generation and biosynthetic purposes. Glutaminases (GAs) convert Gln into glutamate and ammonium. In humans, GAs are encoded by two genes: GLS and GLS2. In glioblastoma, GLS is commonly overexpressed and considered pro-oncogenic. We studied the metabolic effects of inhibiting GLS activity in T98G, LN229, and U87MG human glioblastoma cell lines by using the inhibitor CB-839. We performed metabolomics and isotope tracing experiments using U-13C-labeled Gln, as well as 15N-labeled Gln in the amide group, to determine the metabolic fates of Gln carbon and nitrogen atoms. In the presence of the inhibitor, the results showed an accumulation of Gln and lower levels of tricarboxylic acid cycle intermediates, and aspartate, along with a decreased oxidative labeling and diminished reductive carboxylation-related labeling of these metabolites. Additionally, CB-839 treatment caused decreased levels of metabolites from pyrimidine biosynthesis and an accumulation of intermediate metabolites in the de novo purine nucleotide biosynthesis pathway. The levels of some acetylated and methylated metabolites were significantly increased, including acetyl-carnitine, trimethyl-lysine, and 5-methylcytosine. In conclusion, we analyzed the metabolic landscape caused by the GLS inhibition of CB-839 in human glioma cells, which might lead to the future development of new combination therapies with CB-839.