Human tissue is structured mainly of self-assembled polymers (proteins) and ceramics (bone minerals), with metals present as trace elements with molecular scale functions. However, metals and their alloys have played a predominant role as structural biomaterials in reconstructive surgery, especially orthopedics, with more recent uses in non-osseous tissues, such as blood vessels. With the successful routine use of a large variety of metal implants clinically, issues associated with long-term maintenance of implant integrity have also emerged. This review focuses on metallic implant biomaterials, identifying and discussing critical issues in their clinical applications, including the systemic toxicity of released metal ions due to corrosion, fatigue failure of structural components due to repeated loading, and wearing of joint replacements due to movement. This is followed by detailed reviews on specific metallic biomaterials made from stainless steels, alloys of cobalt, titanium and magnesium, as well as shape memory alloys of nickel–titanium, silver, tantalum and zirconium. For each, the properties that affect biocompatibility and mechanical integrity (especially corrosion fatigue) are discussed in detail. Finally, the most critical challenges for metallic implant biomaterials are summarized, with emphasis on the most promising approaches and strategies.

Metallic implant biomaterials

Epidemiology of tuberculosis

This fifth edition continues the tradition of excellence with thorough coverage of recent trends and changes in the clinical diagnosis and treatment of CNS diseases, detailed relevant neuropathologic, genetic, and clinical findings, and how those changes relate to MRI findings. It remains a comprehensive, internationally acclaimed, state-of-the-art reference for all who have an interest in neuroradiology – trainees to experts in the field, basic science researchers, and clinicians.

Magnetic Resonance Imaging of the Brain and Spine

The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage.A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. 

https://www.ahajournals.org/doi/pdf/10.1161/STR.0000000000000436

2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association

Pathologic grading for prognostic stratification of neuroendocrine tumors (NETs) is critical but presents a challenging interpretive dilemma. Tumor cell proliferative rate is an important factor in the determination of prognosis, and immunohistochemical analysis with Ki67 is becoming more widely used to quantify the proliferative rate. However, Ki67 assessment has limitations due to lack of uniformity and consistency in quantification. These limitations are accentuated in well-differentiated NETs, as differences in the range of 1% to 5% can alter tumor grade, with potential implications for treatment. We therefore performed a concordance study to assess different Ki67 quantification techniques including: (a) digital image analysis (DIA); (b) manual counting (MC) of >2000 cells; and (c) "eyeballed" estimate (EE) of labeling percentage by pathologists (n=18), including individuals experienced in evaluating Ki67 labeling as well as others who had little prior experience assessing Ki67 percentages. Forty-five Ki67 images were selected and analyzed using the 3 methods. On the basis of the recommendations of the World health Organization (WHO) for grading NETs, MC of 2000 cells was used as the "gold standard" reference against which the other techniques were compared. Three images were presented twice, the second being inverted, to assess intraobserver consistency. Statistical analyses were performed to evaluate: (a) the concordance between methods; (b) intraobserver and interobserver consistency; and (c) correlation of NET grades on the basis of Ki67 scores by EE versus the gold standard. Agreement between scores was assessed by intraclass correlation (ICC). DIA and MC were highly concordant (ICC=0.98). The ICC between DIA and the mean EE of all observers was 0.88. However, there was discordance among individual observers on all cases quantified by EE (ICC=0.13). The ICC for intraobserver consistency was 0.39±0.26. With Ki67 in the ranges of 20%, the mean of Ki67 by EE was, respectively, 93%±2%, 55%±7%, and 55%±15% correct against the gold standard. The κ statistics for EE exhibited low agreement (κ=0.24; 95% confidence interval, 0.23-0.25) for all WHO NET grades. Incorrect assessment by EE resulted in upgrading of all WHO G1 group tumors (n=14); in the WHO G2 group, downgrading of 41% cases occurred (n=11) when Ki67 was 5%. We conclude that DIA and MC are the acceptable standards for Ki67 assessment. Given the inherent discordance in determining the grade, the use of an approximate EE of the Ki67-labeling index requires critical reevaluation, especially for NETs with a labeling index straddling the cut-points between grades. Consequently, determination of therapeutic strategies should be guided by an amalgamation of clinicopathologic characteristics, including but not limited to the Ki67 index.

Objective quantification of the Ki67 proliferative index in neuroendocrine tumors of the gastroenteropancreatic system: a comparison of digital image analysis with manual methods.

OBJECTIVE: Tuberculous atlantoaxial dislocation is a rare disease entity. However, tuberculosis continues to be endemic in developing countries. Its earliest clinical presentation may be nonspecific, and delay in diagnosis may lead to irreversible neurological deficit. The management of tuberculous atlantoaxial dislocation includes ventral cervicomedullary decompression, occipitocervicol arthrodesis, and administration of antituberculous medications. METHODS: Eighteen patients with tuberculous atlantoaxial disfocation who presented with neck pain and/or occipital headache, restriction of neck movement, difficulty swallowing, and signs of myelopathy were studied. Four patients had evidence of associated pulmonary tuberculosis. Plain x-rays of the cervical spine, computed tomographic scans, and magnetic resonance images were obtained in all patients for diagnosis and to assess the degree of dislocation and cervicomedullary compression. Simultaneous anterior neural decompression, via a trarnscervical retropharyngeal approach, and posterior arthrodesis were performed on all patients while they remained under anesthesia. Antituberculous chernotherapy was continued for 18 months. RESULTS: Histopathological analysis of excised tissue was consistent with tuberculosis in all patients. However, Ziehl-Neeisen staining for acid-fast bacilli was positive in two cases, and culture for Mycobacterium tuberculosis was negative in all patients. Patients with severe myelopathy experienced marked improvement. One patient died of fulminant resistant tuberculous meningitis. CONCLUSION: The transcervical retropharyngeal approach to the craniovertebral junction provides direct access to the lesion and avoids the potential bacterial contamination of the oral and pharyngeal cavity. It also prevents the development of persistent fistulae. Posterior stabilization should be performed directly after anterior neural decompression, while the patient remains under anesthesia, to prevent neurological deterioration before subsequent posterior fixation. This technique also is help-ful for early mobilization of patients. The aim of surgical treatment should be to obtain biopsy tissue and to perform radical excision of epidural granulation tissue/abscess and infected bone using microsurgical technique. Antituberculous medication must be continued for 18 months with four drug regimens, and continuous monitoring of drug toxicity should be performed throughout the course of treatment.

Surgical management and outcome of tuberculous atlantoaxial dislocation: a 15-year experience.

Various types of tumors and non-tumor lesions arise in the pineal region. This study summarizes the experience the authors have gained with 54 lesions of the pineal region over the last 12 years. Histology was analyzed in all cases. Out of these 54 cases, four were non-tumor lesions. Of the 50 tumors, pineal parenchymal tumors (PPTs) were most common (42% (21/54)), followed by gliomas (40% (20/54)). The PPTs were pineoblastomas (10/21), PPT of intermediate differentiation (7/21), and pineocytomas (4/21). The other tumors included germ cell tumors (4/54), meningiomas (2/54), craniopharyngiomas (2/54), and choroid plexus papilloma (1/54). The non-tumor lesions were epidermoid cysts (2/54), tuberculous abscess (1/54), and cysticercosis (1/54). Immunohistochemically, all the PPTs showed cytoplasmic positivity for synaptophysin. Glial fibrillary acidic protein (GFAP) stained only the reactive astrocytes in these tumors except two cases of pineoblastoma, which showed GFAP positivity in some tumor cells, indicating glial differentiation. There are very few studies of pineal lesions, and there is no study from India in the indexed literature.

Histological analysis of lesions of the pineal region: a retrospective study of 12 years.

BACKGROUND: Clinical and histological criteria for ependymoma prognosis are well recognized. Recently few studies have been done based on Immunohistochemistry for prognostication of these tumours. In this study we have correlated the histlogical spectrum with immmunoexpression of p53 and Ki67 in these tumors. AIMS: To know the incidence of ependymomas; study their morphological spectrum and to evaluate expression of P53 and Ki 67 in diffferent morphological subtypes. MATERIAL AND METHOD: A retrospective sudy was preformed on 70 ependymomas received in a period between 1994 and 2001. Entire tissue received was processed for routine paraffin embedded HE clear cell ependymoma from oligodendroglioma and central neurocytoma; ependymoblastoma from other embryonal tumours. p53 and Ki-67 immunohistochemistry was performed to correlate their expression with various tumour grades and subtypes. RESULTS: There were 3 cases (4.2%) of Grade I ependymoma (2 cases of myxopapillary ependymoma and 1 case of subependymoma); 57 cases (81.5%) of ependymoma grade II (43 of these were of classical variety, 11 of clear cell ependymoma, 2 of papillary and 1 case of cellular ependymoma). There were 9 cases (12.8%) of anaplastic ependymoma (one of these was a clear cell ependymoma and 1 case (1.5%) of ependymoblastoma CONCLUSION: p53 and Ki67 indices can be used in routine diagnostic laboratories to supplement the tumor grade on histology and more studies with follow up should be performed toanalyse the prognsis of different subtypes. The expression of Ki 67 and p53 was significantly higher in anaplastic ependymomas. 4 out of 11 cases of clear cell ependymomas showed higher Ki 67 indices as compared to classical grade II ependymomas, thus further highlighting the importance of differentiating the various subtypes.

/pdf/histological-spectrum-of-ependymomas-and-correlation-of-p53-4w7dt7nu4a.pdf

Histological spectrum of ependymomas and correlation of p53 and Ki-67 expression with ependymoma grade and subtype.

Objective and importance Hypophyseal tuberculomas are extremely rare lesions. The recognition of hypophyseal tuberculomas in the differential diagnosis of pituitary tumors is important, even with no evidence of systemic tuberculosis. Clinical presentation A 27-year-old female patient presented with continuous, dull, generalized headaches and amenorrhea, with no history of visual diminution, galactorrhea, or endocrinological abnormalities and no evidence of systemic tuberculosis. The patient exhibited a normal water balance, without polyuria or polydipsia. A gynecological examination, including an endometrial biopsy for amenorrhea, did not reveal any abnormalities. Perimetric and endocrinological examination results were normal. Contrast magnetic resonance imaging revealed a dense enhancing intrasellar mass, with thickening of the pituitary stalk. Intervention Sublabial rhinoseptal transsphenoidal decompression of the lesion was performed. The histopathological features were consistent with a diagnosis of tuberculoma, and acid-fast bacilli were demonstrated in the surgically removed tissue with Ziehl-Neelsen staining. As soon as the histopathological features were known, the patient underwent a lumbar puncture for cerebrospinal fluid analysis, which indicated normal findings. An intradermal tuberculin test yielded negative results. The patient was treated with medical therapy for 18 months, and complete resolution of the lesion was observed in follow-up examinations. Conclusion Hypophyseal tuberculomas are often mistaken for pituitary adenomas. The finding of a thickened pituitary stalk in contrast magnetic resonance imaging scans may be useful for the differentiation of these lesions from pituitary adenomas. Direct radiosurgery is not an appropriate primary treatment method for pituitary adenomas and is principally restricted to elderly, medically unfit patients with microadenomas and patients with residual or recurrent tumors after microsurgery. It is contraindicated for patients who exhibit a thickened pituitary stalk in contrast magnetic resonance imaging scans.

Hypophyseal tuberculoma: direct radiosurgery is contraindicated for a lesion with a thickened pituitary stalk: case report.

Recurrent tumefactive demyelination in a child.

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