Reducing Salivary Toxicity with Adaptive Radiotherapy (ReSTART): A Randomized Controlled Trial Comparing Conventional IMRT to Adaptive IMRT in Head and Neck Squamous Cell Carcinomas.

BACKGROUND: The utility of Adaptive Radiotherapy (ART) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains to be ascertained. While multiple retrospective and single-arm prospective studies have demonstrated its efficacy in decreasing parotid doses and reducing xerostomia, adequate randomized evidence is lacking. METHODS AND ANALYSIS: ReSTART (Reducing Salivary Toxicity with Adaptive Radiotherapy) is an ongoing phase III randomized trial of patients with previously untreated, locally advanced HNSCC of the oropharynx, larynx, and hypopharynx. Patients are randomized in a 1:1 ratio to the standard Intensity Modulated Radiotherapy (IMRT) arm {Planning Target Volume (PTV) margin 5 mm} vs. Adaptive Radiotherapy arm (standard IMRT with a PTV margin 3 mm, two planned adaptive planning at 10th and 20th fractions). The stratification factors include the primary site and nodal stage. The RT dose prescribed is 66Gy in 30 fractions for high-risk PTV and 54Gy in 30 fractions for low-risk PTV over six weeks, along with concurrent chemotherapy. The primary endpoint is to compare salivary toxicity between arms using salivary scintigraphy 12 months' post-radiation. To detect a 25% improvement in the primary endpoint at 12 months in the ART arm with a two-sided 5% alpha value and a power of 80% (and 10% attrition ratio), a sample size of 130 patients is required (65 patients in each arm). The secondary endpoints include acute and late toxicities, locoregional control, disease-free survival, overall survival, quality of life, and xerostomia scores between the two arms. DISCUSSION: The ReSTART trial aims to answer an important question in Radiation Therapy for HNSCC, particularly in a resource-limited setting. The uniqueness of this trial, compared to other ongoing randomized trials, includes the PTV margins and the xerostomia assessment by scintigraphy at 12 months as the primary endpoint.

Effect of topical and intraventricular antibiotics used during ventriculoperitoneal shunt insertion on the rate of shunt infection-a meta-analysis.

INTRODUCTION: The ventriculoperitoneal shunt is one of the most commonly performed neurosurgical procedures. One of the avoidable complications of shunt surgery is shunt infection. This PRISMA-compliant meta-analysis analysed the effectiveness of topical and/or intraventricular antibiotics in preventing shunt infections in patients undergoing shunt surgery. METHODS: Four databases were searched from inception to 30th June 2021. Only original articles comparing the rate of shunt infection with and without antibiotics were included. Random-effects meta-analysis was used to compare the effect of the use of antibiotics in preventing infection and subgroup analysis for finding differences in various antibiotics. RESULTS: The rate of shunt infection was 2.24% (53 out of 2362) in the topical antibiotic group in comparison to 5.24% (145 out of 2764) in the control group (p = 0.008). Subgroup analysis revealed that there is no significant difference between the antibiotics used. CONCLUSIONS: Our meta-analysis found that the risk of shunt infection is significantly reduced with the use of topical and intraventricular antibiotics without any serious adverse effect. No side effects of topical or intraventricular antibiotics were reported in the included studies. Further prospective studies are required to establish the safety and optimal dosage of topical antibiotics for them to be used routinely in neurosurgical practice. They can be used in patients at high risk of developing shunt infections till such studies are available.

Feasibility of loupe assisted subinguinal varicocelectomy in treatment of male infertility.

OBJECTIVES: To study the impact of loupe assisted subinguinal varicocelectomy on semen quality, serum testosterone level, and spontaneous pregnancy rate. METHODS: The data were prospectively collected for 102 infertile men with clinical varicocele. The preoperative values of semen analysis parameters and serum testosterone level were compared with postoperative values at 6 months. Spontaneous pregnancy was assessed at 6 months. RESULTS: The mean age of patients was 31.56 ±â€¯4.31 years. Primary infertility was reported in 86 patients, while 16 had secondary infertility. Bilateral varicocele was seen in 79 patients while 23 had a unilateral varicocele. The total sperm concentration (×106/mL) before and after varicocelectomy was 12.82 ±â€¯3.91 and 20.06 ±â€¯2.13 respectively (P < .0001). The total sperm motility (%) before and after varicocelectomy was 37.67 ±â€¯7.23 and 55.46 ±â€¯4.51 respectively (P < .0001). The sperm morphology (Kruger/Strict morphology criteria, %) before and after varicocelectomy was 3.11 ±â€¯0.80 and 3.70 ±â€¯0.78 respectively (P < .0001). The serum testosterone level (ng/dL) before and after varicocelectomy was 323.90 ±â€¯67.81 and 396.74 ±â€¯40.88 respectively (P < .0001). The Spontaneous pregnancy rate in couples with primary and secondary infertility was 18.60% and 31.25% respectively. The difference in their rates was not significant (P = .251). The overall spontaneous pregnancy rate was 20.5%. CONCLUSION: Loupe-assisted sub-inguinal varicocelectomy is a safe and effective modality for treating infertile men, particularly when provision for microscopic surgery is unavailable. However, only large size comparative studies or multi-centric trials can confirm this.

Amorphous nickel tungstate films prepared by SILAR method for electrocatalytic oxygen evolution reaction.

Development of electrocatalyst using facile way from non-noble metal compounds with high efficiency for effective water electrolysis is highly demanding for production of hydrogen energy. Nickel based electrocatalysts were currently developed for electrochemical water oxidation in alkaline pH. Herein, amorphous nickel tungstate (NiWO4) was synthesized using the facile successive ionic layer adsorption and reaction method. The films were characterized by X-ray diffraction, Raman spectroscopy, Fourier transfer infrared spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and transmission electron microscopy techniques. The electrochemical analysis showed 315 mV of overpotential at 100 mA cm-2 with lowest Tafel slope of 32 mV dec-1 for oxygen evolution reaction (OER) making films of NiWO4 compatible towards electrocatalysis of water in alkaline media. The chronopotentiometry measurements at 100 mA cm-2 over 24 h showed 97% retention of OER activity. The electrochemical active surface area (ECSA) of NW120 film was 25.5 cm-2.

Cardiac tamponade after superior vena cava stenting.

Superior vena cava (SVC) syndrome results from the blockage of venous blood flow through the SVC, which is caused by either internal obstruction (eg, thrombus) or external compression (eg, thoracic malignancy and infection).1 While thrombus-related SVC syndrome is rising in prevalence, malignancy still accounts for the majority of cases.1 Regardless of cause, SVC syndrome is characterised by facial swelling and plethora, headache and dyspnoea.2 Although venous stenting has become standard of care for treatment of acute SVC syndrome, stent placement presents multiple risks including SVC rupture and cardiac tamponade. In these cases, a high index of suspicion and prompt action are required to avoid an often fatal outcome. Here, we present the case of a patient with cardiac tamponade and subsequent cardiac arrest after SVC stent placement.

Neurosurgery and Neurology Practices during the Novel COVID-19 Pandemic: A Consensus Statement from India.

BACKGROUND: The COVID-19 infection outbreak has aroused increasing attention and affected thousands of people nationwide. The long incubation period, high infectious rate, varied manifestation, and absence of effective treatment make it difficult to manage the disease transmission. OBJECTIVE: The intended goals are to encourage efficient management of neurological and neurosurgical patients, resource utilization, and protecting the healthcare provider during the COVID-19 epidemic. Herein, we present a consensus statement from various centers in India. METHODOLOGY: In addition to the literature review, recommendations were included from neurologists and neurosurgeons from various centers in India. RESULTS: Every patient presenting for treatment should be treated as a potential asymptomatic infected case. Patients should be categorized based upon the priority as acute (require immediate treatment/surgery within 24 h), sub-acute (requiring treatment within a maximum of 7-10 days), or chronic (requiring treatment within a month). Non-essential elective surgeries and outpatient clinics should be avoided after informing the patient(s). There is a high risk of aerosol dispersion during intubation and certain neurosurgical procedures particularly those involving drills and endoscopes. These procedures should be performed wearing full personal protective equipment. The workflow of the operating rooms should also be modified significantly. Minor modifications in personal and professional lifestyles and routine training to use the PPE will ensure efficient management of resources. CONCLUSION: These recommendations could be used to mitigate the risks and reduce exposure to other patients, public, and healthcare staff.

An institutional review of 10 cases of spinal hemangiopericytoma/solitary fibrous tumor.

BACKGROUND: Spinal hemangiopericytoma is very rare tumors with only a few case reports and one case series. We have treated ten patients between 2004 and 2017 and, thus, present a retrospective review of our patients with a focus on clinical presentation, radiological features, management, pathology, and outcome. MATERIALS AND METHODS: Histopathological data were reviewed in all the cases and clinical and follow-up details were collected from data available in our department. RESULTS: There were five males and five females, including one pediatric patient. The mean age of the patients was 34.7 years (Range 12-52 years). Dorsal, cervical, and lumbar spine involvement were found in five, four, and one patient, respectively. Intradural extramedullary tumor was the most common tumor and all patients presented motor weaknesses. Gross total resection of the tumor was done in seven patients and six patients received postoperative radiotherapy. Histopathology showed anaplastic tumor in two cases with high MIB-1 labelling index. Most patients were positive for CD34, vimentin, mic-2, and bcl-2. While the seven patients who underwent gross total resection improved significantly and were self-ambulatory in the follow-up period, two patients who underwent subtotal resection expired due to tumor metastasis. CONCLUSION: Spinal hemangiopericytoma is a very rare tumor. We present a series of cases treated at our institute for the same. Gross total resection is the goal and radiotherapy should be given in case of residual tumor or high-grade tumors. Prognosis is good after gross total excision and functional recovery can be expected in most patients.

Endobronchial valve treatment of persistent alveolopleural fistulae in a patient with cystic fibrosis and empyema.

Persistent air leak (PAL) is a common problem after secondary pneumothorax due to cystic fibrosis (CF). These leaks, caused by either bronchopleural or alveolopleural fistula, are associated with higher morbidity and mortality [1]. Air leaks are traditionally treated with chronic chest tube drainage, chemical pleurodesis, or autologous blood patching in non-surgical candidates [1]. However, these strategies can increase infectious risk or pleural scarring, which are associated with poorer lung transplant surgical outcomes. Endobronchial valve (EBV) placement, while FDA-approved for use in both some surgical PALs and bronchoscopic volume reduction therapy, is one alternative option, but it could theoretically increase the risk of infection, especially in CF patients. Here, we report the case of a CF patient under evaluation for lung transplant who received EBVs for PAL after bilateral secondary spontaneous pneumothoraces.

Successful use of cytarabine and bendamustine in a patient with mantle cell lymphoma and acute renal failure using intermittent hemodialysis: A case report.

Mantle cell lymphoma is a mature B-cell non-Hodgkin lymphoma characterized by the hallmark (11;14) chromosomal translocation, which often presents with lymphadenopathy and extra-nodal involvement. Young, fit patients are generally treated with chemotherapy approaches that incorporate high-dose cytarabine (e.g. the Nordic regimen) followed by autologous hematopoietic cell transplantation. Because of the significant activity of cytarabine in mantle cell lymphoma, increasingly, high- and intermediate-dose cytarabine are being used in the treatment of elderly mantle cell lymphoma patients. In practice, many patients present with significant organ dysfunction and there is limited data on the use of high- to intermediate-dose cytarabine and bendamustine in this setting. Here, we report a case of a critically ill, elderly patient with mantle cell lymphoma and concomitant acute kidney injury and oliguria who was successfully treated with a cycle of cytarabine (Ara-C) and bendamustine accompanied by intermittent hemodialysis.

Phytonutrient composition, antioxidant activity and acceptability of muffins incorporated with red capsicum pomace powder.

Enzymatic liquefaction (EL) ensures fast extraction and enhanced recovery of bioactives from red capsicum along with reduced degradation of these compounds remained in the pomace. Hence, red capsicum pomace obtained as byproduct after EL was freeze dried to produce capsicum pomace powder (CP). CP had almost 80% of bioactives (total carotenoids 91.23 ± 2.35 mg/100 g) and antioxidant activity (DPPH 1.61 ± 0.12 µmol TE/g) compared to fresh pomace. CP was further used to develop muffins. Different concentrations (2-10%) of CP were mixed in wheat flour for preparation of muffins. Wheat flour was fortified with CP at different levels (2-10%) and subsequently, effect of CP fortification on height, texture, bioactives and sensory quality of muffins was observed. CP fortification improved the quality in terms of color, flavor and texture. During storage, hardness values (34.42-32.56 N) showed decreasing trend with increase in CP content. Overall, 6% CP fortification was found most acceptable without causing significant change in porosity and crust uniformity of fortified muffins. Thus, present study demonstrated that fortification of muffins with 6% CP as functional ingredient offers an opportunity to develop quality muffins with enhanced antioxidant activity (DPPH 13.04 ± 0.02 µmol TE/g) and total carotenoids (3.46 ± 2.41 mg/100 g).

Systematic magnetic fluid hyperthermia studies of carboxyl functionalized hydrophilic superparamagnetic iron oxide nanoparticles based ferrofluids.

We have systematically studied heating efficiencies (via specific absorption rate-SAR/intrinsic loss power-ILP) of carboxyl (terephthalic acid-TA) functionalized hydrophilic SPIONs based ferrofluids (with good biocompatibility/high magnetization) and influence of following key factors in magnetic fluid hyperthermia (MFH): (i) alternating magnetic fields (AMFs - H)/frequencies (f) - chosen below/above Hergt's biological safety limit, (ii) concentrations (0.5-8 mg/ml) and (iii) dispersion media (water, a cell-culture medium and triethylene glycol (TEG)) for in vitro cancer therapy. In calorimetric MFH, aqueous ferrofluids have displayed excellent time-dependent temperature rise for the applied AMFs, which resulted in high SAR ranging from 23.4 to 160.7 W/gFe, attributed to the enhanced magnetic responses via π-conjugations of short-chained TA molecules on the surface of SPIONs. Moreover, ILP values up-to 2.5 nHm2/kg (higher than the best commercial ferrofluids) are attained for the aqueous ferrofluids when excited below the recommended safety limit. Besides, the SPIONs dispersed in high viscous TEG have exhibited the highest SAR value (178.8 W/gFe) and reached therapeutic temperatures at faster rates for the lowest concentration due to prominent Neel relaxations. Moreover, these SPIONs have higher killing efficiency towards MCF-7 cancer cells in in vitro studies. Thus, the TA-based ferrofluids have great potential for in vivo/clinical MFH cancer therapies.

Effectiveness of Long Term Supervised and Assisted Physiotherapy in Postsurgery Oral Submucous Fibrosis Patients.

Oral submucous fibrosis is one of the leading potentially malignant disorders prevailing in India. A number of conservative and surgical treatment options have been suggested for this potentially malignant disorder (Arakeri and Brennan, 2013). While the role of physiotherapy has been highlighted in the conservative management, its importance in postsurgical cases to avoid scar contracture and subsequent relapse has not been given due importance in the literature. The following is a case report of a male patient surgically treated for OSMF (oral submucous fibrosis) and meticulously followed up for recalls and physiotherapy. The constant supervision and motivation for physiotherapy along with the constant assistance helped achieve satisfying results.

A clinicopathological study of primary central nervous system lymphomas & their association with Epstein-Barr virus.

BACKGROUND & OBJECTIVES: Primary central nervous system lymphomas (PCNSLs) are relatively uncommon, accounting for 2-3 per cent of primary brain tumours. Majority of these are diffuse large B cell lymphomas (DLBCL) occurring both in immunocompromised and immunocompetent patients. We undertook this study to classify PCNSL into germinal centre (GC) and non-germinal centre (NGC) type based on Hans classification and to find the role of Epstein-Barr virus (EBV) in pathogenesis both by conventional immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). METHODS: The consecutive cases of PCNSL during a 10 years period were analysed by IHC for CD45, CD20, CD3, B-cell lymphoma 2 and 6 (Bcl-2 and Bcl-6), B-cell specific octamer binding protein-1 (BOB-1), multiple myeloma oncogene-1 (MUM-1), EBV latent-membrane protein 1 (LMP-1), cyclin-D1, CD10, CD5 and CD23, as well as by CISH for EBV. RESULTS: During a period of 10 years, 65 PCNSL were diagnosed which comprised 0.69 per cent (65/9476) of all intracranial tumours. The mean age of presentation was 49 yr with sex ratio (M:F) of 1.4:1. Most common location was supratentorial region with predominant involvement of frontal lobe. Single lesions were seen in 38 (58.4%) and multifocal lesions in 27 (41.5%) patients. None of the patients were immunocompromised. All cases were B cell immunophenotype and were DLBCL except one case of follicular lymphoma. According to Hans classification, majority of them were NGC (n=51, 79.6%) and 13 (20.3%) were GC type. Bcl-2 expression was noted in 34 (52.3%) tumours. EBV was positive in three (4.6%) cases; two were detected both by IHC and CISH and one case by CISH only. INTERPRETATION & CONCLUSIONS: In Indian population, PCNSL occurs mainly in immunocompetent patients, and a decade earlier than in western population. Immunophenotyping revealed that all cases were DLBCL with predominance of NGC type. No prognostic difference was seen between GC and NGC DLBCL. Association of EBV was rare and this virus was possibly not involved in the pathogenesis of PCNSL in immunocompetent individuals. CISH was an easy, economical and less cumbersome method for detection of EBV in PCNSL.

Single cannula versus double cannula tracheostomy tubes in major oral and oropharyngeal resections.

OBJECTIVE: To compare the outcomes of two types of tracheostomy tubes used in major head and neck surgery. METHODS: A retrospective study was conducted of prospectively collected data. The post-operative safety and adequacy of a single cannula tracheostomy tube was compared to a double cannula tracheostomy tube in patients undergoing tracheostomy during major oral and oropharyngeal resections. RESULTS: Out of 46 patients with the single cannula tube, 7 (15 per cent) experienced significant obstruction warranting immediate tube removal, while another 9 (20 per cent) needed a change of tube or tube re-insertion for continued airway protection. In contrast, out of 50 patients with the double cannula tube, the corresponding numbers were 0 (p = 0.004) and 1 (2 per cent; p = 0.007) respectively. CONCLUSION: Insertion of a double cannula (instead of a single cannula) tracheostomy tube in the course of major oral and oropharyngeal resections offers better airway protection during the post-operative period.

Early versus delayed decompression in acute subaxial cervical spinal cord injury: A prospective outcome study at a Level I trauma center from India.

AIMS: This study was done with the aim to compare the clinical outcome and patients' quality of life between early versus delayed surgically treated patients of acute subaxial cervical spinal cord injury. The current study was based on the hypothesis that early surgical decompression and fixations in acute subaxial cervical spinal cord trauma is safe and is associated with improved outcome as compared to delayed surgical decompression. MATERIALS AND METHODS: A total of 69 patients were recruited and divided into early decompression surgery Group A (operated within 48 h of trauma; n = 23) and late/delayed decompression surgery Group B (operated between 48 h and 7 days of trauma; n = 46). The patients in both groups were followed up, and comparative differences noted in the neurological outcome, quality of life, and bony fusion. RESULTS: The early surgery group spent lesser days in the intensive care unit and hospital (Group A 28.6 vs. Group B 35 days) had lesser postoperative complications (Group A 43% vs. Group B 61%) and a reduced mortality (Group A 30% vs. Group B 45%). In Group A, 38% patients had 1 American Spinal Injury Association (ASIA) grade improvement while 31% experienced >2 ASIA grade improvement. In Group B, the neurological improvement was 27% and 32%, respectively (P = 0.7). There was a significant improvement in the postoperative quality of life scores in both groups. CONCLUSION: Early surgery in patients with acute subaxial cervical spine injury should be considered strongly in view of the lesser complications, early discharge, and reduced mortality.

Tachycardia in breast reconstructive microsurgery: Affirmation of the IMA tachycardia syndrome.

INTRODUCTION: The internal mammary vessels are frequently chosen as recipient vessels for breast free flap reconstruction. We have noticed that when using the internal mammary recipients that these patients have a propensity for tachycardia that was not previously observed. Our aim was to investigate the factors related to perioperative tachycardia in the microsurgical breast reconstruction population and to address whether use of the internal mammary system is a causative factor in tachycardia. METHODS: A retrospective chart review was conducted to identify patients who underwent abdominal-based microvascular breast reconstruction at the Washington University School of Medicine between 2002 and 2012 to identify the presence of tachycardia. After application of exclusion criteria, 76 microvascular abdominal-based free flap reconstructions were identified. The internal mammary (IM) TRAM group (n = 24) and the thoracodorsal (TD) TRAM group (n = 52) were compared. A binomial logistic regression was performed with the presence of tachycardia as the dependent variable. RESULTS: There was a higher incidence of tachycardia in the IM TRAM group when compared to the TD TRAM group (p = 0.004). The variables predictive of tachycardia in our logistic regression model were IMA recipient (p = 0.04), need for transfusion (p = 0.03), and presence of fever (p = 0.01). CONCLUSION: Our study reaffirms that there are several factors that are predictive of tachycardia in the setting of microvascular breast reconstruction. The IMA syndrome should be a recognized cause of tachycardia as using these recipient vessels are shown to be predictive of postoperative tachycardia as shown in our study.

p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy during limb immobilization.

Immobilization causes skeletal muscle atrophy via complex signaling pathways that are not well understood. To better understand these pathways, we investigated the roles of p53 and ATF4, two transcription factors that mediate adaptations to a variety of cellular stresses. Using mouse models, we demonstrate that 3 days of muscle immobilization induces muscle atrophy and increases expression of p53 and ATF4. Furthermore, muscle fibers lacking p53 or ATF4 are partially resistant to immobilization-induced muscle atrophy, and forced expression of p53 or ATF4 induces muscle fiber atrophy in the absence of immobilization. Importantly, however, p53 and ATF4 do not require each other to promote atrophy, and coexpression of p53 and ATF4 induces more atrophy than either transcription factor alone. Moreover, muscle fibers lacking both p53 and ATF4 are more resistant to immobilization-induced atrophy than fibers lacking only p53 or ATF4. Interestingly, the independent and additive nature of the p53 and ATF4 pathways allows for combinatorial control of at least one downstream effector, p21. Using genome-wide mRNA expression arrays, we identified p21 mRNA as a skeletal muscle transcript that is highly induced in immobilized muscle via the combined actions of p53 and ATF4. Additionally, in mouse muscle, p21 induces atrophy in a manner that does not require immobilization, p53 or ATF4, and p21 is required for atrophy induced by immobilization, p53, and ATF4. Collectively, these results identify p53 and ATF4 as essential and complementary mediators of immobilization-induced muscle atrophy and discover p21 as a critical downstream effector of the p53 and ATF4 pathways.

Systems-based discovery of tomatidine as a natural small molecule inhibitor of skeletal muscle atrophy.

Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy.