Carboplatin Plus Vincristine as an Alternative Chemotherapeutic Scheme in Patients With Glioblastoma.

Background and objective Alternative chemotherapy regimens, including cisplatin, carmustine, or other agents, have been shown to be effective; however, the use of carboplatin plus vincristine (C/V) has not been studied before. In this study, we aimed to determine the survival rates in patients treated with C/V, by comparing our findings with treatments based on temozolomide (TMZ), and to explore a possible relationship with the methylation status of the methylguanine methyltransferase (MGMT) promoter in patients with glioblastoma (GB). Methods A retrospective cohort study was conducted involving 45 surgically treated patients diagnosed with GB. Fresh tissue samples were examined by the DNA bisulfite conversion method to determine methylation status. After surgery, different chemotherapy regimens were employed as adjuvants. Follow-up of participants was performed as outpatients at three-month intervals to determine overall survival (OS), by comparing the use of TMZ versus C/V. Results MGMT promoter methylation status could only be determined in 35 samples; 20 patients received adjuvant chemotherapy, of which 14 were treated with C/V and six with TMZ-based schemes. The median OS (mOS) was eight months (range: 1-24 months). OS was 57.25% at six months, 48.7% at 12 months, and 28.5% at 24 months. In the TMZ group, an OS of 83% was observed at 24 months. In the C/V group, OS was 71.4% at six months, 57.1% at 12 months, and 35.7% at 24 months. Patients who did not receive adjuvant chemotherapy treatment had the lowest survival rates with an OS of 39.9% at six months, 26.6% at 12 months, and 19.9% ​​at 24 months. Conclusions Based on our findings, C/V offers an accessible and effective alternative treatment when the TMZ-based scheme is not accessible, providing higher rates of OS compared to patients without chemotherapy management. The methylation status of the MGMT promoter is a significant prognostic factor, resulting in higher survival rates among patients when it is methylated.

The hallucal interphalangeal ossicle: anatomy and basis for ultrasound-guided surgical shaving.

Painful lesions on the plantar aspect of the first interphalangeal joint (IPJ) of the hallux can be attributed to structures called ossicles, nodules, or sesamoids. The aims of the present study were first to verify that ultrasonography (US) is a high-sensitivity tool for diagnosing an interphalangeal ossicle (IO), and second to prove that US-guided-shaving surgery ("milling") is a safe and feasible technique for remodeling the IO. The study is divided into three parts. In the first part, the prevalence of IOs was estimated in 12 cadaver feet using US, anatomical dissection, and fluoroscopy. In the second, a detailed US and morphological description of the IO was obtained. In the third, six cadaver feet were subjected to surgical milling. IO prevalence was 41.6% in gross anatomy, 41.6% in US examination and just 16.6% in fluoroscopy. The ossicles had a mean length of 4 mm (± 2 mm) and a width of 7 mm (± 2 mm). The ossicles could be completely shaved in all specimens without injuring important anatomical structures. Our results indicate that US is a more precise tool for diagnosing an IO than X-ray. Moreover, our US-guided mini-invasive surgical technique appears feasible and safe.

Anatomic mapping of the collateral branches of the external carotid artery with regard to daily clinical practice.

BACKGROUND: To identify the anatomical variations of the main branches of the external carotid artery (lingual, facial, occipital, ascending pharyngeal and sternocleidomastoid), giving information about the calibers and origins with the aim of creating a new classification useful in clinical practice. MATERIAL AND METHODS: 193 human embalmed body-donors were dissected. The data collected were analyzed using the Chi² test. The results of previous studies were reviewed. RESULTS: The majority of the anterior arterial branches (superior thyroid, facial and lingual artery) were observed with an independent origin, respectively, classified as pattern I (80.83%, 156/193). In 17.62% (34/193) a linguofacial trunk, pattern II, has been observed, only in 1,04% (2/193) a thyrolingual trunk, pattern III, has been found and in one case (1/193, 0.52%) one thyrolinguofacial trunk, pattern IV, was found. Depending on the posterior branches (occipital and ascending pharyngeal), four different types could be determined: type a, the posterior arteries originated independently, type b, the posterior arteries originated in a common trunk, type c, the ascending pharyngeal artery was absent, type d, the occipital artery was absent. CONCLUSION: Anatomical variations in these arteries are relevant in daily clinical practice due to growing applications, e.g., in Interventional Radiology techniques. Knowledge of these anatomical references could help clinicians in the interpretation of the carotid system.

Clinical Relevance of Corticosteroid Withdrawal on Graft Histological Lesions in Low-Immunological-Risk Kidney Transplant Patients.

The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.

Impact of HLA Mismatching on Early Subclinical Inflammation in Low-Immunological-Risk Kidney Transplant Recipients.

The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06-1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04-2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions.

Anatomical basis of a safe mini-invasive technique for lengthening of the anterior gastrocnemius aponeurosis.

BACKGROUND: The surgical procedure itself of lengthening the gastrocnemius muscle aponeurosis is performed to treat multiple musculoskeletal, neurological and metabolical pathologies related to a gastro-soleus unit contracture such as plantar fasciitis, Achilles tendinopathy, metatarsalgia, cerebral palsy, or diabetic foot ulcerations. Therefore, the aim of our research was to prove the effectiveness and safety of a new ultrasound-guided surgery-technique for the lengthening of the anterior gastrocnemius muscle aponeurosis, the "GIAR"- technique: the gastrocnemius-intramuscular aponeurosis release. METHODS AND RESULTS: An ultrasound-guided surgical GIAR on ten fresh-frozen specimens (10 donors, 8 male, 2 females, 5 left and 5 right) was performed. Exclusion criteria of the donated bodies to science were BMI above 35 (impaired ultrasound echogenicity), signs of traumas in the ankle and crural region, a history of ankle or foot ischemic vascular disorder, surgery or space-occupying mass lesions. The surgical procedures were performed by two podiatric surgeons with more than 6 years of experience in ultrasound-guided procedures. The anterior gastrocnemius muscle aponeurosis was entirely transected in 10 over 10 specimens, with a mean portal length of 2 mm (± 1 mm). The mean gain at the ankle joint ROM after the GIAR was 7.9° (± 1.1°). No damages of important anatomical structures could be found. CONCLUSION: Results of this study indicate that our novel ultrasound-guided surgery for the lengthening of the anterior gastrocnemius muscle aponeurosis (GIAR) might be an effective and safe procedure.

Anatomic basis for a new ultrasound-guided, mini-invasive technique for release of the deep transverse metatarsal ligament.

INTRODUCTION: Morton's neuroma is an entrapment neuropathy of the third common plantar digital nerve, caused by the deep transverse metatarsal ligament (DTML). Minimally invasive or percutaneous surgery is a very common procedure, but surgical effectivity of this technique remains controversial. The goal of our study was to prove the effectiveness and safety of a new ultrasound-guided technique for DTML-release in a cadaver model. MATERIALS, METHODS, AND RESULTS: The DTML was visualized in 10 fresh frozen donated body to science-feet (eight male and two females, five left and five right) using an US device (GE Logic R7; 13 MHz linear probe, Madrid, Spain). Consecutively, minimally invasive ultrasound-guided surgery was performed. Exclusion criteria of the donated bodies to science were previous history of forefoot surgery and space occupying mass lesions. The complete release of the ligament was achieved in all specimens without damage of any important anatomical structures as proven by anatomical dissection. CONCLUSIONS: The results of this study indicate that our novel approach of an ultrasound-guided release of the DTML is safer and more effective compared to blind techniques. The DTML could reliably be visualized and securely cut through a dorsal, minimally invasive surgical incision of only 2 mm.

Ultrasound-guided decompression surgery of the distal tarsal tunnel: a novel technique for the distal tarsal tunnel syndrome-part III.

BACKGROUND: The aim of this study was to provide a safe ultrasound-guided minimally invasive surgical approach for a distal tarsal tunnel release concerning nerve entrapments. METHODS AND RESULTS: The study was carried out on ten fresh-frozen feet. All of them have been examined by high-resolution ultrasound at the distal tarsal tunnel. The surgical approach has been marked throughout the course of the medial intermuscular septum (MIS, the lateral fascia of the abductor hallucis muscle). After the previous steps, nerve decompression was carried out through a MIS release through a 2.5 mm (± 0.5 mm) surgical portal. As a result, an effective release of the MIS has been obtained in all fresh-frozen feet. CONCLUSION: The results of our anatomic study indicate that this novel ultrasound-guided minimally invasive surgical approach for the release of the MIS might be an effective, safe and quick decompression technique treating selected patients with a distal tarsal tunnel syndrome.

Extracranial Course of the Facial Nerve Revisited.

INTRODUCTION: The extrapetrous course of the facial nerve has been a matter of study and debate since XIX century. Two different classifications have been classically proposed and widely accepted by most of the authors. Nevertheless, there are reported cases which do not fit in any of those. The aim of this study is to propose a new and useful classification. MATERIAL AND METHODS: We have used 23 embalmed Caucasian adult cadavers (11 male and 12 female) belonging to the Bodies Donation and Dissecting Rooms Centre of the University Complutense of Madrid. The extra-petrous facial nerve was dissected in the possible specimens resulting in 38 facial nerves. The studied parameters were length, diameter of divisions, terminal branches, and nerve connections. RESULTS: In every specimen two main divisions were found, temporofacial and cervicofacial. They divided into five terminal branches from cranial to caudal: temporal, zygomatic, buccal, marginal or mandibular, and cervical. Based on the comparison with previous proposed classifications, we have unified the patterns in 12 types being the most frequent types the type 3 (eight cases, 21.05%), with connections between temporal, zygomatic and buccal branches and the type 8 (eight cases, 21.05%), a complex network between temporal, zygomatic, buccal, and mandibular branches. The number of terminal branches was so variable. CONCLUSION: We propose a new 12-patterned classification which summarizes the previous ones. However, we consider that a good study of the number of terminal branches, connections between branches or with other cranial nerves are more useful for surgeons to avoid injuries to the facial nerve during surgery than complex classifications. Anat Rec, 302:599-608, 2019. © 2018 Wiley Periodicals, Inc.

The Human Laryngeal Innervation Revisited-The Role of the Neural Connections.

In spite that vascular inconvenients or immunological rejections have been solved in relation with larynx transplant, a successful functional reinnervation has not been achieved. Some studies have suggested that laryngeal nerve connection may contain motor fibers, which could explain unexpected evoked responses in electromyographic studies or the different positions adopted of the vocal folds after similar nerve lesions. Ten patients with unexpected evoked responses after laryngeal nerve stimulation were selected. All the patients underwent a total laryngectomy due to oncological causes. In every case, laryngeal nerve connections were observed. All of them were morphologic and histologic processed for choline-acetyltransferase immunohistochemistry. The presence of motor axons in the nerve connections has been demonstrated, which would explain that the motor innervation to the laryngeal muscles could be dual through these variable connections. This also would justify the difficulty of carrying out laryngeal nerve reinnervation procedures. Anat Rec, 302:646-651, 2019. © 2018 Wiley Periodicals, Inc.

Ultrasound-guided decompression surgery of the tarsal tunnel: a novel technique for the proximal tarsal tunnel syndrome-Part II.

BACKGROUND: The aim of this study is to provide a safe ultrasound-guided minimally invasive surgical approach for a proximal tarsal tunnel release concerning nerve entrapments. METHODS AND RESULTS: The study was carried out on ten fresh-frozen feet. All of them were examined by high resolution ultrasound at the medial ankle region. The surgical approach was marked throughout the course of the flexor retinaculum (laciniate ligament). Once the previous steps were done, the flexor retinaculum release technique was carried out with a 2-mm entry only. As a result, an effective and safe release of the flexor retinaculum was obtained in all fresh-frozen feet. CONCLUSION: The results of our anatomic study indicate that our novel ultrasound-guided minimally invasive surgical approach for the release of the flexor retinaculum might be an effective, safe and quick decompression technique treating selected patients with a proximal tarsal tunnel syndrome.

C3 glomerulonephritis associated with monoclonal gammopathy of renal significance: case report.

BACKGROUND: Morbidity associated with monoclonal gammopathy of renal significance is high due to the severe renal lesions and the associated systemic alterations. Accordingly, early diagnosis is fundamental, as is stopping the clonal production of immunoglobulins using specific chemotherapy. CASE PRESENTATION: A 75-year-old man with chronic renal disease of unknown origin since 2010 experienced rapid worsening of renal function over a period of 6 mos. Bone marrow biopsy showed monoclonal gammopathy of undetermined significance. Kidney biopsy showed the presence of C3 glomerulonephritis, with exclusive deposits of C3 visible on immunofluorescence and a membranoproliferative pattern on light microscopy. Skin biopsy showed endothelial deposition of complement. Given both the renal and cutaneous involvement the patient was considered to have monoclonal gammopathy of renal significance. We considered an underlying pathogenic mechanism for the renal alteration secondary to activation of the alternative complement pathway by the anomalous immunoglobulin. Despite treatment with plasmapheresis, bortezomib and steroids, advanced chronic kidney disease developed. CONCLUSIONS: The possible underlying cause of the monoclonal gammopathy of renal significance suggests that monoclonal gammopathy should be considered in adult patients with membranoproliferative glomerulonephritis.

Cigarette Smoking, Alcohol Consumption and Overweight in Multiple Sclerosis: Disability Progression.

BACKGROUND: The rate at which disability progresses in multiple sclerosis (MS), and its severity, have been associated with modifiable lifestyle habits. OBJECTIVE: To investigate the risk of disability progression in MS patients according to tobacco and alcohol consumption and to the presence of overweight. METHODS: This was a follow-up of MS cases from a concluded case-control study (National Institute of Neurology and Neurosurgery, Mexico 2010-2013). The evolution in EDSS (Expanded Disability Scale Score) units was followed through a medical record review. Kaplan Meier statistics and multivariate Cox regression analysis were performed. RESULTS: Of 181 cases, 63.5% were women and 82.5% had relapsing remitting MS. Study duration was 19.95 ± 15.24 months. The disease progressed faster in daily smokers than in non-smokers (p = 0.0168). In overweight patients, disability progressed faster than in normal weight patients (p = 0.0249). Ex-consumers of alcohol had lower risk of progression than current consumers (HR = 0.33 CI 95% = 0.14-0.83, p = 0.019) and both daily and ex-smokers presented higher risk of progression than non-smokers (HR = 2.32 CI 95% = 1.14-4.72, p = 0.020 and HR = 3.56, CI 95% = 1.21-10.46, p = 0.021). Stratifying by gender, the effects of smoking and overweight were only found in men. CONCLUSIONS: Smoking is associated with rapid disability progression in MS. Our results suggest that cessation of tobacco and alcohol consumption could be clinically beneficial. Although there is association between overweight and disability progression in men, a further exploration of gender differences is necessary to corroborate this finding.

Clinical prognostic factors in adults with astrocytoma: Historic cohort.

OBJECTIVE: To explore the clinical prognostic factors for adults affected with astrocytoma. PATIENTS AND METHODS: Using a historic cohort, we selected 155 clinical files from patients with astrocytoma using simple randomization. The main outcome variable was overall survival time. To identify clinical prognostic factors, we used bivariate analysis, Kaplan Meier, the log rank test and the Cox regression models. The number of lost years lived with disability (DALY) based on prevalence, was calculated. RESULTS: The mean age at diagnosis was 45.7 years. Analysis according to tumour stage, including grades II, III and IV, also showed a younger age of presentation. Kaplan-Meier survival estimates showed that tumour grade, Karnofsky status (KPS) ≥70, resection type, chemotherapy, radiotherapy, alcohol consumption, familial history of cancer and clinical presentation were significantly associated with survival time. Using a proportional hazard model, age, grade IV, resection, chemotherapy+radiotherapy and KPS were identified as prognostic factors.The amount of life lost due to premature death in this population was 28 years. CONCLUSION: In our study, astrocytoma was diagnosed in young adults. The overall survival was 15 months, 9% (n=14) of patients presented a survival of 2 years, and 3% of patients survived 3 years. On average the number of years lost due to premature death and disability was 28.53 years.

Reorganization of laryngeal motoneurons after crush injury in the recurrent laryngeal nerve of the rat.

Motoneurons innervating laryngeal muscles are located in the nucleus ambiguus (Amb), but there is no general agreement on the somatotopic representation and even less is known on how an injury in the recurrent laryngeal nerve (RLN) affects this pattern. This study analyzes the normal somatotopy of those motoneurons and describes its changes over time after a crush injury to the RLN. In the control group (control group 1, n = 9 rats), the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were injected with cholera toxin-B. In the experimental groups the left RLN of each animal was crushed with a fine tip forceps and, after several survival periods (1, 2, 4, 8, 12 weeks; minimum six rats per time), the PCA and TA muscles were injected as described above. After each surgery, the motility of the vocal folds was evaluated. Additional control experiments were performed; the second control experiment (control group 2, n = 6 rats) was performed labeling the TA and PCA immediately prior to the section of the superior laryngeal nerve (SLN), in order to eliminate the possibility of accidental labeling of the cricothyroid (CT) muscle by spread from the injection site. The third control group (control group 3, n = 5 rats) was included to determine if there is some sprouting from the SLN into the territories of the RLN after a crush of this last nerve. One week after the crush injury of the RLN, the PCA and TA muscles were injected immediately before the section of the SLN. The results show that a single population of neurons represents each muscle with the PCA in the most rostral position followed caudalwards by the TA. One week post-RLN injury, both the somatotopy and the number of labeled motoneurons changed, where the labeled neurons were distributed randomly; in addition, an area of topographical overlap of the two populations was observed and vocal fold mobility was lost. In the rest of the survival periods, the overlapping area is larger, but the movement of the vocal folds tends to recover. After 12 weeks of survival, the disorganization within the Amb is the largest, but the number of motoneurons is similar to control, and all animals recovered the movement of the left vocal fold. Our additional controls indicate that no tracer spread to the CT muscle occurred, and that many of the labeled motoneurons from the PCA after 1 week post-RLN injury correspond to motoneurons whose axons travel in the SLN. Therefore, it seems that after RLN injury there is a collateral sprouting and collateral innervation. Although the somatotopic organization of the Amb is lost after a crush injury of the RLN and does not recover in the times studied here, the movement of the vocal folds as well as the number of neurons that supply the TA and the PCA muscles recovered within 8 weeks, indicating that the central nervous system of the rat has a great capacity of plasticity.

Functional role of human laryngeal nerve connections.

OBJECTIVES/HYPOTHESIS: Current knowledge of the functional role of human laryngeal nerves is based on traditional laryngeal neuroanatomic descriptions or contradictory electromyographic studies. The aim of this study was to clarify the functional role of neural connections between laryngeal nerves by correlating the different electromyographic patterns observed after laryngeal stimulation and the existence of different neural connections. STUDY DESIGN: Descriptive. METHODS: Electromyographic and morphologic study in 13 patients during total laryngectomy procedure. RESULTS: Seven patients showed an additional evoked response from the cricothyroid muscle after recurrent laryngeal nerve stimulation. External laryngeal nerve stimulation resulted in additional responses from the posterior cricoarytenoid muscle in three cases and from the arytenoid muscle in one. The presence of a neural connection was confirmed in all patients who showed an unexpected electromyographic response. CONCLUSIONS: The different connections between laryngeal nerves are at least partially of motor nature and play a role in the mobility of vocal folds.

Human laryngeal ganglia contain both sympathetic and parasympathetic cell types.

The presence of ganglia associated with the laryngeal nerves is well documented. In man, these ganglia have been less well studied than in other species and, in particular, the cell types within these ganglia are less well characterized. Using a panel of antibodies to a variety of markers found in the paraganglion cells of other species, we were able to show the existence of at least two populations of cells within human laryngeal paraganglia. One population contained chromogranin and tyrosine hydroxylase representing a neurosecretory population possibly secreting dopamine. A second population of choline acetyltransferase positive cells would appear to have a putative parasympathetic function. Further work is needed to characterize these cell populations more fully before it will be possible to assign functions to these cell types but our results are consistent with the postulated functions of these ganglia as chemoreceptors, neurosecretory cells, and regulators of laryngeal mucus secretion.

Anatomical variations of the superior thyroid and superior laryngeal arteries.

BACKGROUND: There are known to be variations in the origins of the superior thyroid artery (STA), an important surgical landmark, and 1 of its branches, the superior laryngeal artery (SLA). METHODS: Three hundred thirty human embalmed heminecks were dissected. The results of previous studies were reviewed, and a meta-analysis is presented. RESULTS: Four different origins for the STA were found. The most frequent was type I, from the carotid bifurcation (49%). Four different origins were also found for the SLA being the most frequent the type I in which the artery arose from STA (78%). The mean external diameters of STA and SLA were 0.26 and 0.20 cm, respectively, with no statistically significant differences by side or sex. CONCLUSION: Variations in the origin of STA and SLA from the carotid arterial tree and the similarity of their diameters mean that there is a significant possibility of their misidentified during surgery.