Regulation of DNA Damage Response by RNA/DNA-Binding Proteins: Implications for Neurological Disorders and Aging.

RNA-binding proteins (RBPs) are evolutionarily conserved across most forms of life, with an estimated 1,500 RBPs in humans. Traditionally associated with post-transcriptional gene regulation, RBPs contribute to nearly every known aspect of RNA biology, including RNA splicing, transport, and decay. In recent years, an increasing subset of RBPs have been recognized for their DNA binding properties and involvement in DNA transactions. We refer to these RBPs with well-characterized DNA binding activity as RNA/DNA binding proteins (RDBPs), many of which are linked to neurological diseases. RDBPs are associated with both nuclear and mitochondrial DNA repair. Furthermore, the presence of intrinsically disordered domains in RDBPs appears to be critical for regulating their diverse interactions and plays a key role in controlling protein aggregation, which is implicated in neurodegeneration. In this review, we discuss the emerging roles of common RDBPs from the heterogeneous nuclear ribonucleoprotein (hnRNP) family, such as TAR DNA binding protein-43 (TDP43) and fused in sarcoma (FUS) in controlling DNA damage response (DDR). We also explore the implications of RDBP pathology in aging and neurodegenerative diseases and provide a prospective on the therapeutic potential of targeting RDBP pathology mediated DDR defects for motor neuron diseases and aging.

Comparison of Platelet-Rich Plasma and Corticosteroid Injections for Chronic Plantar Fasciitis: A Randomized Controlled Trial.

BACKGROUND: Plantar fasciitis is a common and debilitating foot condition, with varying treatment options and inconsistent outcomes. The objective of this study was to assess and compare the effectiveness of autologous platelet-rich plasma (PRP) injections and corticosteroid injections in treating persistent plantar fasciitis. METHODS: In this study, a total of 70 patients suffering from chronic plantar fasciitis were randomly divided into two groups, i.e., one receiving PRP injections (n=35) and the other receiving corticosteroid injections (n=35). The visual analog scale (VAS) was used to assess pain outcomes, while the American Orthopaedic Foot and Ankle Society (AOFAS) score was used to assess functional status. Patients were assessed before the injection and then followed up at 15 days, one month, three months, and six months after the injection. RESULTS: The baseline VAS and AOFAS scores were similar between the two groups. However, the PRP group showed significantly greater improvements in VAS and AOFAS scores compared to the corticosteroid group at the one-month, three-month, and six-month follow-ups (p<0.05). The PRP group had a higher proportion of patients with mild or moderate pain and better functional outcomes at later time points. CONCLUSIONS: Autologous PRP injections are superior to corticosteroid injections in terms of long-term pain alleviation and functional improvement for patients suffering from chronic plantar fasciitis. Platelet-rich plasma should be regarded as a feasible therapeutic choice for this condition, especially in individuals who have not shown improvement with conservative treatment.

Correlation Between Radiological and Functional Outcomes Following Operative and Nonoperative Management of Acetabular Fractures: A Prospective Observational Study.

INTRODUCTION: The management of acetabular fractures is a complicated orthopedic procedure that has been advancing with time. Newer radiological tools like CT scans help surgeons to identify and manage these fractures more attentively. The study was conducted to evaluate the clinical and radiographic outcomes in patients with acetabular fractures managed either conservatively or by open reduction and internal fixation. MATERIALS AND METHOD: The study was done on 35 patients aged 18-60 years, with acetabular fractures treated either surgically or conservatively. Clinical scorings and radiological scoring were only taken and noted at three- and six-month intervals using Matta's radiographic scoring and modified Merle d'Aubigne and Postel clinical hip scoring. Clinico-radiological variables and complications were compared between the two groups. The data obtained was subjected to statistical analyses using IBM Statistical Package of Social Sciences (SPSS) 2.0 version software (Chicago, IL, USA) at a level of significance being p<0.05. RESULTS:  Out of a total of 35 patients, 19 were treated surgically and 16 conservatively. In patients belonging to the surgical treatment group, a maximum of 57.9% were aged 40-50 years, whereas the maximum patients (50%) of the conservative treatment group were aged <40 years, with male predominance in both groups. The type of fracture was recorded according to Judet and Letournel in both groups. Merle d'Aubigne's scoring and Matta's hip score were recorded at three and six months in both groups. A positive correlation was seen between radiological and functional outcomes at three and six months, which means that the higher the radiological scoring, the better the functional outcome of the patient managed either conservatively or surgically in the entire cohort. CONCLUSION:  Our study revealed that surgically managed patients had better functional and radiological outcomes than the patients who were conservatively managed at six months of follow-up. However, this is associated with more complications depending on fracture complexity and initial presentation of hip dislocation. The higher the radiological scoring, the better the functional outcome of the patient managed either conservatively or surgically in the entire cohort.

FUS unveiled in mitochondrial DNA repair and targeted ligase-1 expression rescues repair-defects in FUS-linked motor neuron disease.

This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3's repair role, resulting in increased mtDNA damage and mutations. These alterations cause various manifestations of mitochondrial dysfunction, particularly under stress conditions relevant to disease pathology. Importantly, rectifying FUS mutations in patient-derived induced pluripotent cells (iPSCs) preserves mtDNA integrity. Similarly, targeted introduction of human DNA Ligase 1 restores repair mechanisms and mitochondrial activity in FUS mutant cells, suggesting a potential therapeutic approach. Our findings unveil FUS's critical role in mitochondrial health and mtDNA repair, offering valuable insights into the mechanisms underlying mitochondrial dysfunction in FUS-associated motor neuron disease.

Urbanization alters the spatiotemporal dynamics of plant-pollinator networks in a tropical megacity.

Urbanization is a major driver of biodiversity change but how it interacts with spatial and temporal gradients to influence the dynamics of plant-pollinator networks is poorly understood, especially in tropical urbanization hotspots. Here, we analysed the drivers of environmental, spatial and temporal turnover of plant-pollinator interactions (interaction ß-diversity) along an urbanization gradient in Bengaluru, a South Indian megacity. The compositional turnover of plant-pollinator interactions differed more between seasons and with local urbanization intensity than with spatial distance, suggesting that seasonality and environmental filtering were more important than dispersal limitation for explaining plant-pollinator interaction ß-diversity. Furthermore, urbanization amplified the seasonal dynamics of plant-pollinator interactions, with stronger temporal turnover in urban compared to rural sites, driven by greater turnover of native non-crop plant species (not managed by people). Our study demonstrates that environmental, spatial and temporal gradients interact to shape the dynamics of plant-pollinator networks and urbanization can strongly amplify these dynamics.

FUS Unveiled in Mitochondrial DNA Repair and Targeted Ligase-1 Expression Rescues Repair-Defects in FUS-Linked Neurodegeneration.

This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3's repair role, resulting in increased mtDNA damage and mutations. These alterations cause various manifestations of mitochondrial dysfunction, particularly under stress conditions relevant to disease pathology. Importantly, rectifying FUS mutations in patient-derived induced pluripotent cells (iPSCs) preserves mtDNA integrity. Similarly, targeted introduction of human DNA Ligase 1 restores repair mechanisms and mitochondrial activity in FUS mutant cells, suggesting a potential therapeutic approach. Our findings unveil FUS's critical role in mitochondrial health and mtDNA repair, offering valuable insights into the mechanisms underlying mitochondrial dysfunction in FUS-associated neurodegeneration.

Adverse Drug Reaction Patterns of First-line Anti-tubercular Drugs among Saharia Tuberculosis Patients: An Observational Study in Particularly Vulnerable Tribal Group of Madhya Pradesh, India.

SUMMARY: The Saharia tribe of Madhya Pradesh has a very high tuberculosis (TB) burden. However, there is no report of adverse drug reaction (ADR) available in patients receiving anti-TB chemotherapy in the community. Reporting and monitoring of ADRs among TB patients is still rare in marginalized communities. An observational prospective study was performed from November 2019 to June 2020 to assess the patterns of ADRs in 250 Saharia TB patients, who were prescribed Category-I daily DOTS (HRZE) by the physician. Both male and female participants equally experienced ADR during the treatment, but relatively more females (92.6%) than males (88.6%) reported ADR during Phase I. Out of 250 patients, 224 patients (89.6%) experienced one or more ADRs in Phase I. The central nervous system-related (75.6%) ADR was mostly reported followed by any gastrointestinal (74.4%), cardiovascular (49.2%) and any dermatological related (44.4%) ADRs. It is paramount to timely monitor and proactively manages ADRs pertaining to anti-TB drug treatment with minimal alteration in the treatment course.

Functional diversity of farmland bees across rural-urban landscapes in a tropical megacity.

Urbanization poses a major threat to biodiversity and food security, as expanding cities, especially in the Global South, increasingly compete with natural and agricultural lands. However, the impact of urban expansion on agricultural biodiversity in tropical regions is overlooked. Here we assess how urbanization affects the functional response of farmland bees, the most important pollinators for crop production. We sampled bees across three seasons in 36 conventional vegetable-producing farms spread along an urbanization gradient in Bengaluru, an Indian megacity. We investigated how landscape and local environmental drivers affected different functional traits (sociality, nesting behavior, body size, and specialization) and functional diversity (functional dispersion) of bee communities. We found that the functional responses to urbanization were trait specific with more positive than negative effects of gray area (sealed surfaces and buildings) on species richness, functional diversity, and abundance of most functional groups. As expected, larger, solitary, cavity-nesting, and, surprisingly, specialist bees benefited from urbanization. In contrast to temperate cities, the abundance of ground nesters increased in urban areas, presumably because larger patches of bare soil were still available beside roads and buildings. However, overall bee abundance and the abundance of social bees (85% of all bees) decreased with urbanization, threatening crop pollination. Crop diversity promotes taxonomic and functional diversity of bee communities. Locally, flower resources promote the abundance of all functional groups, and natural vegetation can maintain diverse pollinator communities throughout the year, especially during the noncropping season. However, exotic plants decrease functional diversity and bee specialization. To safeguard bees and their pollination services in urban farms, we recommend (1) preserving seminatural vegetation (hedges) around cropping fields to provide nesting opportunities for aboveground nesters, (2) promoting farm-level crop diversification of beneficial crops (e.g., pulses, vegetables, and spices), (3) maintaining native natural vegetation along field margins, and (4) controlling and removing invasive exotic plants that disrupt native plant-pollinator interactions. Overall, our results suggest that urban agriculture can maintain functionally diverse bee communities and, if managed in a sustainable manner, be used to develop win-win solutions for biodiversity conservation of pollinators and food security in and around cities.

Mycobacterium tuberculosis strain lineage in mixed tribal population across India and Andaman Nicobar Island.

In India, the tribal population constitutes almost 8.6% of the nation's total population. Despite their large presence, there are only a few reports available on Mycobacterium tuberculosis (M. tb) strain prevalence in Indian tribal communities considering the mobile nature of this population and also the influence of the mainstream populations they coexist within many areas for their livelihood. This study attempts to provide critical information pertaining to the TB strain diversity, its public health implications, and distribution among the tribal population in eleven Indian states and Andaman & Nicobar (A&N) Island. The study employed a population-based molecular approach. Clinical isolates were received from 66 villages (10 states and Island) and these villages were selected by implying situation analysis. A total of 78 M. tb clinical isolates were received from 10 different states and A&N Island. Among these, 16 different strains were observed by spoligotyping technique. The major M. tb strains spoligotype belong to the Beijing, CAS1_DELHI, and EAI5 family of M. tb strains followed by EAI1_SOM, EAI6_BGD1, LAM3, LAM6, LAM9, T1, T2, U strains. Drug-susceptibility testing (DST) results showed almost 15.4% of clinical isolates found to be resistant to isoniazid (INH) or rifampicin (RMP) + INH. Predominant multidrug-resistant (MDR-TB) isolates seem to be Beijing strain. Beijing, CAS1_DELHI, EAI3_IND, and EAI5 were the principal strains infecting mixed tribal populations across India. Despite the small sample size, this study has demonstrated higher diversity among the TB strains with significant MDR-TB findings. Prevalence of Beijing MDR-TB strains in Central, Southern, Eastern India and A&N Island indicates the transmission of the TB strains.

Experiences and needs of patients with MDR/XDR-TB: a qualitative study among Saharia tribe in Madhya Pradesh, Central India.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) continues to be a major public health threat posing a critical challenge to TB treatment and control worldwide. The present study was conducted among patients with DR-TB of the Saharia tribe residing in Madhya Pradesh state of Central India to document their experiences and needs, and to identify gaps for treatment adherence as this population is known to be poor because of migration and other factors. METHODS: We conducted 16 in-depth interviews on purposively selected patients with DR-TB among the Saharia tribe using a predesigned open-ended in-depth interview guide, which included questions on domains like general physical health, diagnosis, treatment adherence, side-effects of drugs and experience related to the health facility. Out of these interviews, various subthemes were extracted. The obtained qualitative data were subjected to thematic analysis. RESULTS: The study helped to understand the experiences and needs of the patients with DR-TB in various stages from diagnosis to treatment. Also, there was the impact of factors like lack of education and awareness, poor living conditions and lack of healthcare facilities on predominance of the disease in the community. Poor access to a healthcare facility, high pill burden and related side-effects, longer duration of treatment, financial burden, misbeliefs and misconceptions were prominent issues posing a challenge to treatment adherence. The narratives pointed out their struggle at every stage be it with diagnosis, treatment initiation or treatment adherence. CONCLUSION: It is paramount to address the needs and experiences of patients with DR-TB to develop a patient-centric and context-specific approach conducive to the sociocultural set-up of tribal people. This will scale down the attrition rate of tribal patients while adhering to the complete treatment process and reducing the high burden of TB among the Saharia community. In addition, tribal patients should be counselled at regular intervals to increase their confidence in the treatment.

Understanding health care-seeking behaviour of the tribal population in India among those with presumptive TB symptoms.

BACKGROUND AND OBJECTIVES: Understanding the drivers for care-seeking among those who present with symptoms of TB is crucial for early diagnosis of TB and prompt treatment, which will in turn halt further TB transmission. While TB is a challenge among the tribal population, little is known about the care-seeking behaviour and the factors influencing care-seeking behaviour among the tribal population across India. METHODOLOGY: This community-based descriptive study was carried out in 17 states of India across 6 zones, covering 88 villages from tribal districts with over 70% tribal population. The sample population included individuals ≥15 years old who were screened through an interview for symptoms suggestive of pulmonary TB (PTB), currently and/or previously on anti-TB treatment. Those with symptoms were then assessed on their health-seeking behavior using a semi-structured interview schedule. RESULTS: Among 74532 eligible participants screened for symptoms suggestive of TB, 2675 (3.6%) were found to be presumptive TB cases. Of them, 659 (24.6%) sought care for their symptoms. While 48.2% sought care after a week, 19.3% sought care after one month or more, with no significant difference in the first point of care; 46.9% approaching a private and 46.7% a public facility. The significant factors influencing care-seeking behaviour were knowledge on TB (OR: 4.64 (3.70-5.83), p < 0.001), age<35 years (OR: 1.60 (1.28-2.00), p < 0.001), co-morbidities like asthma (OR: 1.80 (1.38-2.35), p < 0.001) and blood pressure (OR: 2.59 (1.75-3.85), p < 0.001), symptoms such as blood in sputum (OR: 1.69 (1.32-2.16), p < 0.001), shortness of breath (OR: 1.43 (1.19-1.72), p < 0.001) and weight loss (OR: 1.59 (1.33-1.89), p < 0.001). The cough was the most often reported symptom overall. There were gender differences in symptoms that prompted care-seeking: Males were more likely to seek care for weight loss (OR: 1.78 (1.42-2.23), p<0.001), blood in the sputum (OR: 1.69 (1.25-2.28), p<0.001), shortness of breath (OR: 1.49 (1.18-1.88), p<0.001) and fever (OR: 1.32 (1.05-1.65), p = 0.018). Females were more likely to seek care for blood in sputum (OR: 1.68 (1.10-2.58), p = 0.018) and shortness of breath (OR = 1.35, (1.01-1.82), p = 0.048). The cough did not feature as a significant symptom that prompted care-seeking. CONCLUSION: Delayed healthcare-seeking behaviour among those with symptoms presumptive of TB in the tribal population is a major concern. Findings point to differences across gender about symptoms that prompt care-seeking in this population. Gender-sensitive interventions with health system strengthening are urgently needed to facilitate early diagnosis and treatment among this population.

Cranial and intra-axial metastasis originating from a primary ovarian Dysgerminoma.

Dysgerminomas are aggressive germ cell tumors that typically have a favorable prognosis, especially in patients diagnosed with early stage disease. We recount the history of a 23-year-old woman who was treated for a stage IA ovarian dysgerminoma in November 2017. Postoperatively, the patient was noncompliant insofar as obtaining routine lab evaluations; ten months later, she was diagnosed with a cranial metastasis that extended into the meninges. The patient subsequently underwent a posterior fossa craniotomy and adjuvant etoposide, bleomycin and cisplatin chemotherapy to which she initially responded; however, during cycle 4, she developed pancytopenia whereupon the chemotherapy was summarily discontinued. Thereafter, the patient was surveilled and currently, she remains in clinical remission. Early stage ovarian dysgerminoma, albeit rarely, has the capacity to metastasize to the cranium or brain, further underscoring the significance of employing active follow-up with these patients.

Recurrence of tuberculosis among newly diagnosed sputum positive pulmonary tuberculosis patients treated under the Revised National Tuberculosis Control Programme, India: A multi-centric prospective study.

INTRODUCTION: There is lack of information on the proportion of new smear-positive pulmonary tuberculosis (PTB) patients treated with a 6-month thrice-weekly regimen under Revised National Tuberculosis Control Programme (RNTCP) who develop recurrent TB after successful treatment outcome. OBJECTIVE: To estimate TB recurrence among newly diagnosed PTB patients who have successfully completed treatment and to document endogenous reactivation or re-infection. Risk factors for unfavourable outcomes to treatment and TB recurrence were determined. METHODOLOGY: Adult (aged ≥ 18 yrs) new smear positive PTB patients initiated on treatment under RNTCP were enrolled from sites in Tamil Nadu, Karnataka, Delhi, Maharashtra, Madhya Pradesh and Kerala. Those declared "treatment success" at the end of treatment were followed up with 2 sputum examinations each at 3, 6 and 12 months after treatment completion. MIRU-VNTR genotyping was done to identify endogenous re-activation or exogenous re-infection at TB recurrence. TB recurrence was expressed as rate per 100 person-years (with 95% confidence interval [95%CI]). Regression models were used to identify the risk factors for unfavourable response to treatment and TB recurrence. RESULTS: Of the1577 new smear positive PTB patients enrolled, 1565 were analysed. The overall cure rate was 77% (1207/1565) and treatment success was 77% (1210 /1565). The cure rate varied from 65% to 86%. There were 158 of 1210 patients who had TB recurrence after treatment success. The pooled TB recurrence estimate was 10.9% [95%CI: 0.2-21.6] and TB recurrence rate per 100 person-years was 12.7 [95% CI: 0.4-25]. TB recurrence per 100 person-years varied from 5.4 to 30.5. Endogenous reactivation was observed in 56 (93%) of 60 patients for whom genotyping was done. Male gender was associated with TB recurrence. CONCLUSION: A substantial proportion of new smear positive PTB patients successfully treated with 6 -month thrice-weekly regimen have TB recurrence under program settings.

A comparative study of the socio-economic risk factors for pulmonary tuberculosis in the Saharia tribe of Madhya Pradesh, India.

Background: To determine the socio-economic risk factors for pulmonary tuberculosis (PTB) in the Saharia tribal community in Madhya Pradesh, Central India. Methods: PTB cases detected during the year 2013-14 through a community active TB prevalence survey in the Shivpuri district, Madhya Pradesh were included in the study. For each case, three controls were selected randomly among the non-cases from the same village and the data on socio-economic risk factors were collected. Using logistic regression analysis, the risk factors for PTB disease were identified. Results: A total of 220 cases and 660 controls participated in the study. Of the 13 risk factors studied, on multivariate analysis the risk of PTB was found to be significantly associated with malnutrition (adjusted odds ratio [AOR] 2.02 [95% confidence interval {CI} 1.46 to 2.79]), living in a kaccha (built of naturally occurring materials) house (AOR 2.72 [95% CI 1.44 to 5.11]) and tobacco smoking (mostly beedis; AOR 1.59 [95% CI 1.12 to 2.18]). Conclusions: The findings highlight that malnutrition, poor living conditions in a Kaccha house (built of naturally occurring materials) and tobacco smoking are the major risk factors for PTB among Saharias, which need to be studied among other tribal populations in the country. There is a need to strengthen health and nutrition programmes in this community.

Idiopathic thoracic spinal cord herniation.

Idiopathic spinal cord herniation represents an uncommon and unique diagnostic entity, most commonly affecting middle-aged individuals, with a nearly twofold female predilection. It most characteristically affects the mid-thoracic spine, with the herniation occurring ventrally or ventrolaterally. Clinical presentation is typically a slowly-progressive myelopathy, with Brown-Séquard syndrome occurring more frequently than spastic paraparesis. Diagnosis is made by imaging, with high-resolution or phase-contrast MR sequences and/or CT myelography. Treatment should be individualized, with options including conservative management with routine follow-up and surgical intervention. We review the literature on this interesting topic and report on, and present our technique for, operative reduction and repair of idiopathic spinal cord herniation in a 66 year-old woman.

Clinical and Procedural Predictors of Outcomes From the Endovascular Treatment of Posterior Circulation Strokes.

BACKGROUND AND PURPOSE: Patients with posterior circulation strokes have been excluded from recent randomized endovascular stroke trials. We reviewed the recent multicenter experience with endovascular treatment of posterior circulation strokes to identify the clinical, radiographic, and procedural predictors of successful recanalization and good neurological outcomes. METHODS: We performed a multicenter retrospective analysis of consecutive patients with posterior circulation strokes, who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique [ADAPT] approach). We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. RESULTS: A total of 100 patients were included in the final analysis (mean age, 63.5±14.2 years; mean admission National Institutes of Health Stroke Scale score, 19.2±8.2). Favorable clinical outcome at 3 months (modified Rankin Scale score ≤2) was achieved in 35% of patients. Successful recanalization and shorter time from stroke onset to the start of the procedure were significant predictors of favorable clinical outcome at 90 days. Stent retriever and aspiration thrombectomy as primary treatment approaches showed comparable procedural and clinical outcomes. None of the baseline advanced imaging modalities (magnetic resonance imaging, computed tomographic perfusion, or computed tomography angiography assessment of collaterals) showed superiority in selecting patients for thrombectomy. CONCLUSIONS: Time to the start of the procedure is an important predictor of clinical success after thrombectomy in patients with posterior circulation strokes. Both stent retriever and aspiration thrombectomy as primary treatment approaches are effective in achieving successful recanalization.

Impact of surgical methodology on the complication rate and functional outcome of patients with a single brain metastasis.

OBJECT Brain metastases are the most common intracranial neoplasms and are on the increase. As radiation side effects are increasingly better understood, more patients are being treated with surgery alone with varying outcomes. The authors previously reported that en bloc resection of a single brain metastasis was associated with decreased incidences of leptomeningeal disease and local recurrence compared with piecemeal resection. However, en bloc resection is often feared to cause an increased incidence of postoperative complications. This study aimed to answer this question. METHODS The authors reviewed data from patients with a previously untreated single brain metastasis, who were treated with resection at The University of Texas M.D. Anderson Cancer Center (1993-2012). Data related to the patient, tumor, and methods of resection were obtained. Discharge Karnofsky Performance Scale (KPS) scores and 30-day postoperative complications were noted. Complications were considered major when they persisted for longer than 30 days, resulted in hospitalization or prolongation of hospital stay, required aggressive treatment, and/or were life threatening. RESULTS During the study period, 1033 eligible patients were identified. The median age was 58 years, 83% had a KPS score greater than 70, and 81% were symptomatic at surgery. Sixty-two percent of the patients underwent en bloc resection of their tumor, and 38% underwent piecemeal resection. There were significant differences between the 2 groups in terms of preoperative tumor volume, tumor functional grade, and symptoms at presentation, among others. The overall complication rates were 13% for patients undergoing en bloc resection and 19% for patients undergoing piecemeal resection (p = 0.007). The incidences of major complications and neurological complications were also significantly different. There was a trend in the same direction for major neurological complications, although it was not significant. Among patients undergoing piecemeal resection of tumors in eloquent cortex, 24% had complications (13% had major, 18% had neurological, 9% had major neurological, and 13% had select neurological complications; 4% died within 1 month of surgery). Among those undergoing en bloc resection of such tumors, 11% had complications (6% had major, 8% had neurological, 4% had major neurological, and 4% had select neurological; 2% died within 1 month of surgery). The differences in overall, major, neurological, and select neurological complications were statistically significant, but 1-month mortality and major neurological complications were not. In addition, within subcategories of tumor volume, the incidence of various complications was generally higher for patients undergoing piecemeal resection than for those undergoing en bloc resection. CONCLUSIONS The authors' results indicate that postoperative complication rates are not increased by en bloc resection, including for lesions in eloquent brain regions or for large tumors. This gives credence to the idea that en bloc resection of brain metastases, when feasible, is at least as safe as piecemeal resection.

Incidence and clinical implications of carotid branch occlusion following treatment of internal carotid artery aneurysms with the pipeline embolization device.

BACKGROUND: The use of flow diverters such as the pipeline embolization device (PED) for treatment of intracranial aneurysms carries the risk of side branch occlusion. OBJECTIVE: To determine the incidence and clinical outcomes associated with supraclinoid internal carotid artery (ICA) branch occlusion after deployment of PEDs for ICA aneurysms. METHODS: We reviewed patients who underwent endovascular treatment with PEDs for ICA aneurysms between June 2011 and March 2013. Forty-nine patients (43 women, mean age 56.3±1.8 years, 68 aneurysms) in whom PEDs traversed the origin of supraclinoid ICA branches (ophthalmic [OA], posterior communicating [PcommA], and anterior choroidal artery [AChA]) were selected for this study. Follow-up angiograms (mean follow-up, 12.8±0.8 months) were studied to determine the location of PEDs and the patency of ICA branches. RESULTS: PEDs were placed across the ostia of 49 OAs, 14 PcommAs, and 11 AChAs. Multiple PEDs were deployed in 16 patients. Rate of branch occlusion was 4% (2/49) for the OA, 7.1% (1/14) for the PcommA, and 0% for the AChA. Patients with branch occlusion did not endure new neurological deficits. ICA branch occlusion was not associated with the number of PEDs covering the ostia (P=.76) or the origin of ICA branches from the aneurysm (P=.24). CONCLUSION: The incidence of major supraclinoid ICA branch occlusion after treatment with PEDs was low. These events were not associated with new neurological deficits nor were they related to the number of PEDs deployed or the origin of ICA branches from the aneurysm.

The 1-piece transbasal approach: operative technique and anatomical study.

OBJECT: The transbasal approach (TBA) is an anterior skull base approach, which provides access to the anterior skull base, sellar-suprasellar region, and clivus. The TBA typically involves a bifrontal craniotomy with orbital bar and/or nasal bone osteotomies performed in 2 separate steps. The authors explored the feasibility of routinely performing this approach in 1 piece with a quantitative cadaveric anatomical study, and present an operative case example of their approach. METHODS: Seven latex-injected cadaveric heads underwent a 1-piece TBA, followed by additional bone removal typical for a traditional 2-piece approach. Six surgical angles relative to the pituitary stalk, as well as the surface area of the orbital roof osteotomy, were measured before and after additional bone removal. The vertical angle from the frontonasal suture to the foramen cecum was measured in all specimens. In addition to an anatomical study, the authors have used this technique in the operating room, and present an illustrative case of resection of an anterior skull base meningioma. RESULTS: Morphometric results were as follows: the vertical angle from the frontonasal suture to the foramen cecum ranged from 17.4° to 29.7° (mean 23.8° ± 4.8°) superiorly. Of the 6 surgical angle measures, only the middle horizontal angle was increased in the 2-piece versus the 1-piece approach (mean 43.4° ± 4.6° vs 43.0° ± 4.3°, respectively; p = 0.049), with a mean increase of 0.4°. The surface area of the orbital osteotomy was increased in the 2-piece versus the 1-piece approach (mean 2467 mm(2) ± 360 mm(2) vs 2045 mm(2) ± 352 mm(2), respectively; p < 0.001). The patient in the illustrative clinical case had a good outcome, both clinically and cosmetically. CONCLUSIONS: The 1-piece TBA provides an alternative to the traditional 2-piece approach. It allows easier reconstruction, potentially decreased operative time, and improved cosmesis. While more of the orbital roof can be removed with the 2-piece approach, this additional bone removal offers only a small increase in 1 of 6 surgical angles that were measured.