Impact of therapeutic inhibition of oncogenic cell signaling tyrosine kinase on cell metabolism: in vivo-detectable metabolic biomarkers of inhibition.

BACKGROUND: Inhibition of kinases is the ever-expanding therapeutic approach to various types of cancer. Typically, assessment of the treatment response is accomplished by standard, volumetric imaging procedures, performed weeks to months after the onset of treatment, given the predominantly cytostatic nature of the kinase inhibitors, at least when used as single agents. Therefore, there is a great clinical need to develop new monitoring approaches to detect the response to kinase inhibition much more promptly. Noninvasive 1H magnetic resonance spectroscopy (MRS) can measure in vitro and in vivo concentration of key metabolites which may potentially serve as biomarkers of response to kinase inhibition. METHODS: We employed mantle cell lymphoma (MCL) cell lines demonstrating markedly diverse sensitivity of inhibition of Bruton's tyrosine kinase (BTK) regarding their growth and studied in-depth effects of the inhibition on various aspects of cell metabolism including metabolite synthesis using metabolomics, glucose and oxidative metabolism by Seahorse XF technology, and concentration of index metabolites lactate, alanine, total choline and taurine by 1H MRS. RESULTS: Effective BTK inhibition profoundly suppressed key cell metabolic pathways, foremost pyrimidine and purine synthesis, the citrate (TCA) cycle, glycolysis, and pyruvate and glutamine/alanine metabolism. It also inhibited glycolysis and amino acid-related oxidative metabolism. Finally, it profoundly and quickly decreased concentration of lactate (a product of mainly glycolysis) and alanine (an indicator of amino acid metabolism) and, less universally total choline both in vitro and in vivo, in the MCL xenotransplant model. The decrease correlated directly with the degree of inhibition of lymphoma cell expansion and tumor growth. CONCLUSIONS: Our results indicate that BTK inhibition exerts a broad and profound suppressive effect on cell metabolism and that the affected index metabolites such as lactate, alanine may serve as early, sensitive, and reliable biomarkers of inhibition in lymphoma patients detectable by noninvasive MRS-based imaging method. This kind of imaging-based detection may also be applicable to other kinase inhibitors, as well as diverse lymphoid and non-lymphoid malignancies.

The Burden of Protozoal and Helminth Intestinal Infections and Related Risk Factors Among the Households of Migrant Construction Workers in Bhopal.

There are a few existing gaps and paucity of literature from Southeast Asia on the prevalence of intestinal parasitic infections among migrant construction workers. The present cross-sectional study was conducted to address this gap among migrant construction workers and their households in Bhopal. The study design included an interview questionnaire survey prior to the enrollment of participants and stool sample collection. The stool samples were processed according to the study protocol of macroscopy, occult blood testing, microscopy techniques combined with modified acid-fast, and sedimentation techniques. Participants were deemed positive if they exhibited microscopic findings in one out of three stool samples per recruit. We recommended clinical consultation for these cases and provided a report. Direct therapeutic intervention was not part of the study. The total recruits were 361. The predominant age group was young, i.e., aged 21 to 30 years (122/361, 33.8%), with the majority of females (55.2%). Most workers were occupied with work of digging soil (47.4%). The majority of participants (93.1%) practiced open field defecation (OFD). The prevalence of intestinal parasitic infections among migrant workers and households was 36.9% (133/361). Monoinfection was 88.7%, with 41% from Entamoeba histolytica/Entamoeba dispar. Monoinfection with Hymenolepis nana (10.2%) was a predominant helminth. The most common coinfection observed was of Giardia intestinalis with Ancylostoma duodenale (26.7%). Hand washing was the only independent predictor with an odds ratio of 3.6. Migrant behavior of the construction workers and their households was the major reason for not reaching the benefits of deworming schemes for children and vulnerability to intestinal parasitic infections.

Lonidamine Induced Selective Acidification and De-Energization of Prostate Cancer Xenografts: Enhanced Tumor Response to Radiation Therapy.

Prostate cancer is a multi-focal disease that can be treated using surgery, radiation, androgen deprivation, and chemotherapy, depending on its presentation. Standard dose-escalated radiation therapy (RT) in the range of 70-80 Gray (GY) is a standard treatment option for prostate cancer. It could be used at different phases of the disease (e.g., as the only primary treatment when the cancer is confined to the prostate gland, combined with other therapies, or as an adjuvant treatment after surgery). Unfortunately, RT for prostate cancer is associated with gastro-intestinal and genitourinary toxicity. We have previously reported that the metabolic modulator lonidamine (LND) produces cancer sensitization through tumor acidification and de-energization in diverse neoplasms. We hypothesized that LND could allow lower RT doses by producing the same effect in prostate cancer, thus reducing the detrimental side effects associated with RT. Using the Seahorse XFe96 and YSI 2300 Stat Plus analyzers, we corroborated the expected LND-induced intracellular acidification and de-energization of isolated human prostate cancer cells using the PC3 cell line. These results were substantiated by non-invasive 31P magnetic resonance spectroscopy (MRS), studying PC3 prostate cancer xenografts treated with LND (100 mg/kg, i.p.). In addition, we found that LND significantly increased tumor lactate levels in the xenografts using 1H MRS non-invasively. Subsequently, LND was combined with radiation therapy in a growth delay experiment, where we found that 150 µM LND followed by 4 GY RT produced a significant growth delay in PC3 prostate cancer xenografts, compared to either control, LND, or RT alone. We conclude that the metabolic modulator LND radio-sensitizes experimental prostate cancer models, allowing the use of lower radiation doses and diminishing the potential side effects of RT. These results suggest the possible clinical translation of LND as a radio-sensitizer in patients with prostate cancer.

Metabolic Imaging Biomarkers of Response to Signaling Inhibition Therapy in Melanoma.

Dabrafenib therapy for metastatic melanoma focuses on blocking growth-promoting signals produced by a hyperactive BRAF protein. We report the metabolic differences of four human melanoma cell lines with diverse responses to dabrafenib therapy (30 mg/kg; oral): WM3918 < WM9838BR < WM983B < DB-1. Our goal was to determine if metabolic changes produced by the altered signaling pathway due to BRAF mutations differ in the melanoma models and whether these differences correlate with response to treatment. We assessed metabolic changes in isolated cells using high-resolution proton magnetic resonance spectroscopy (1H MRS) and supplementary biochemical assays. We also noninvasively studied mouse xenografts using proton and phosphorus (1H/31P) MRS. We found consistent changes in lactate and alanine, either in isolated cells or mouse xenografts, correlating with their relative dabrafenib responsiveness. In xenografts, we also observed that a more significant response to dabrafenib correlated with higher bioenergetics (i.e., increased ßNTP/Pi). Notably, our noninvasive assessment of the metabolic status of the human melanoma xenografts by 1H/31P MRS demonstrated early metabolite changes preceding therapy response (i.e., tumor shrinkage). Therefore, this noninvasive methodology could be translated to assess in vivo predictive metabolic biomarkers of response in melanoma patients under dabrafenib and probably other signaling inhibition therapies.

Effect of Heartfulness meditation program on perceived stress and satisfaction with life of female students.

Though literacy levels are slowly improving in India due to the steps taken by the Government of India, it has been a challenge for female students with gender disparities in literacy levels. Stress levels are high in students, more so during their exam times. While prior literature has demonstrated the prevalence of stress during student life, there is limited evidence of any interventions to decrease stress and improve satisfaction with life, specifically for female students. Heartfulness meditation is a heart-based meditation practice that may reduce stress and improve satisfaction with life among female students. We conducted a prospective cohort analysis comparing perceived stress and satisfaction with life outcomes among female students who self-selected to participate in the Heartfulness meditation program. The first group, G20, underwent intervention from week 0 until week 12 and continued their practice independently until week 20. The second group, G14, joined the intervention from week 7 until week 12 with only a 6-week exposure to guided meditation sessions through Heartfulness Trainers. They continued their practice independently until week 20. Data on Perceived Stress (PSS) and Satisfaction with Life (SWLS) were collected at week 0 and week 20 for both groups. G20 had 127 participants, and G14 had 113 participants. Ninety-four participants from the G20 group and 93 from G14 completed the study. The G20 group showed a statistically significant reduction of PSS scores from 20.79 to 18.96, and an increase in the SWLS scores from 22.03 to 23.51 from baseline to the end of the study period. The study of the Pearson correlation coefficient indicated that there is a weak positive correlation between pre- and post-scores for both the groups for both PSS and SWLS. Our findings suggest that Heartfulness meditation practice offers significant benefits with perceived stress and satisfaction with life among female students independent of their age. Still, a prolonged guided intervention of over 6 weeks is needed. A larger, randomized study with an additional control group with no meditation intervention is recommended. Clinical trial registration: ISRCTN11302156, https://doi.org/10.1186/ISRCTN11302156.

A Retrospective Study of Maxillofacial Fractures at a Tertiary Care Centre in North India: A Review of 1674 Cases.

Objective: To examine the pattern of maxillofacial fractures in patients treated at the SMS Hospital in Jaipur, India, over a two-year period. Methods: A retrospective study was conducted from October 2019 to September 2021, which recorded various data of patients with maxillofacial fractures, including age, sex, site distribution, cause of injury, type of facial bone fractures, soft tissue injuries, dentoalveolar trauma, and type of treatment. The days spent in the hospital before and after surgery were also recorded. Results: The study included 1674 patients, with a male-to-female ratio of 4.07:1 and males being the most affected at 80.3%. The most common cause of injury was road traffic accidents (53.5%), followed by falls (18.6%) and assaults (16.1%). Mandibular fractures accounted for 38% of all fractures, with the parasymphysis being the most common site for fractures. Open reduction and internal fixation (ORIF) and intermaxillary fixation (IMF) were the most common treatment options for mandibular fractures. Conclusion: The study highlights the need for strict enforcement of traffic rules and road safety laws, along with education and preventive measures to reduce the incidence of maxillofacial trauma. The pattern of maxillofacial injuries can provide useful information for designing programs towards the prevention and management of maxillofacial trauma.

pH-dependent structural characteristics of lonidamine: 1H and 13C NMR study.

Lonidamine (LND) is an anti-cancer drug with great potential as a metabolic modulator of chemotherapy, radiotherapy, hyperthermia, and photodynamic therapy in cancer treatment. LND affects several important aspects of cancer cell metabolism: it inhibits Complex I and II of the electron transport chain (ETC) and pyruvate carriers (mitochondrial), and monocarboxylate transporters in the plasma membrane of the cell. Cancer cells are affected by changes in pH on the molecular level, and so are the drugs used to treat cancer, thus it is important to understand how pH affects their structures and LND is no exception. LND dissolves at a pH of 8.3 in tris-glycine buffer but has limited solubility at pH 7. To understand how pH affects the structure of LND, and its effect as a metabolic modulator on cancer therapy, we made up samples of LND at pH 2, pH 7, and pH 13, and analyzed these samples using 1H and 13C NMR. We looked for ionization sites to explain the behavior of LND in solution. Our results showed considerable chemical shifts between the extremes of our experimental pH range. LND was ionized at its indazole α-nitrogen, however, we did not directly observe the protonation of the carboxyl group oxygen that is expected at pH 2, which may be the result of a chemical-exchange phenomenon.

Microstructural and Microvascular Alterations in Psychotic Spectrum Disorders: A Three-Compartment Intravoxel Incoherent Imaging and Free Water Model.

BACKGROUND AND HYPOTHESIS: Microvascular and inflammatory mechanisms have been hypothesized to be involved in the pathophysiology of psychotic spectrum disorders (PSDs). However, data evaluating these hypotheses remain limited. STUDY DESIGN: We applied a three-compartment intravoxel incoherent motion free water imaging (IVIM-FWI) technique that estimates the perfusion fraction (PF), free water fraction (FW), and anisotropic diffusion of tissue (FAt) to examine microvascular and microstructural changes in gray and white matter in 55 young adults with a PSD compared to 37 healthy controls (HCs). STUDY RESULTS: We found significantly increased PF, FW, and FAt in gray matter regions, and significantly increased PF, FW, and decreased FAt in white matter regions in the PSD group versus HC. Furthermore, in patients, but not in the HC group, increased PF, FW, and FAt in gray matter and increased PF in white matter were significantly associated with poor performance on several cognitive tests assessing memory and processing speed. We additionally report significant associations between IVIM-FWI metrics and myo-inositol, choline, and N-acetylaspartic acid magnetic resonance spectroscopy imaging metabolites in the posterior cingulate cortex, which further supports the validity of PF, FW, and FAt as microvascular and microstructural biomarkers of PSD. Finally, we found significant relationships between IVIM-FWI metrics and the duration of psychosis in gray and white matter regions. CONCLUSIONS: The three-compartment IVIM-FWI model provides metrics that are associated with cognitive deficits and may reflect disease progression.

Selection of Suitable Protein Structure from Protein Data Bank: An Important Step in Structure-based Drug Design Studies.

The selection of a protein structure is an important step for the success of the drug discovery process using structure-based design. Selection of the right crystal structure is critical as multiple crystal structures are available for the same protein in the Protein Data Bank (PDB). In this communication, we have discussed a systematic approach for selecting the right type of protein structure. Selecting crystal structures of TACE, 11ß-HSD1, DprE1, and SARS-CoV-2 Mpro enzymes for some case studies have been discussed for illustration.

Feasibility of Non-invasive Measurement of Tumour NAD(H) by In Vivo Phosphorus-31 Magnetic Resonance Spectroscopy.

Importance of the redox status of nicotinamide adenine dinucleotide (NAD), including its oxidized (NAD+) and reduced (NADH) forms, has been shown in many biological processes. However, NAD(H) redox status assessment is traditionally limited to biochemical assays in vitro or optical redox imaging (ORI) for superficial tissues in vivo and for deep tissues ex vivo. In recent years, phosphorous-31 magnetic resonance spectroscopy (31P-MRS) was utilized to quantify NAD+, NADH, and the redox ratio NAD+/NADH in normal tissues in vivo. The quantification is based on the spectral fitting of the upfield shoulder of the αATP peak that contains signals of NAD+ (a quartet) and NADH (a singlet), assuming pH-independence of peak positions. To evaluate the feasibility of measuring tumour NAD(H) redox status in vivo, we fitted single voxel 31P-MR spectra of subcutaneous mouse xenografts of human breast cancer cell lines acquired on a 9.4-T horizontal bore preclinical MR scanner. We found larger variations in the chemical shift offsets of NAD+ and NADH from αATP in these tumours than the literature values of normal tissues. Furthermore, our 31P-MR spectra of αATP, NAD+, and NADH solution phantoms indicated that the chemical shift of αATP and thus the offsets between NAD(H) and αATP were pH dependent. Therefore, whether tumour pH should be incorporated into the spectral fitting model should be further evaluated. Additionally, spectral resolution and signal-to-noise ratio should be improved by optimising 31P-MRS protocols, increasing data acquisition time, and using a more sensitive coil for signal detection.

Assessment of Nicotinamide Adenine Dinucleotide in Human Tissues by In Vivo Phosphorus-31 Magnetic Resonance Spectroscopic Imaging at 1.5 Tesla.

As a phosphorus-containing molecule, nicotinamide adenine dinucleotide is visible by phosphorus magnetic resonance spectroscopy (31P-MRS). However, the relatively low cellular levels of its oxidised (NAD+) and reduced (NADH) forms and a significant peak overlap hinder their evaluation in live tissues. This problem is critical when using 31P-MR spectroscopic imaging, where signals are localised from limited tissue volumes. We have reported improvements in spectral resolution of 31P-MRSI of human tissues in situ using a strict optimisation of the static magnetic field (B0 shimming) and 1H-irradiation during 31P acquisition. Given this, we aimed to demonstrate if these improvements allowed us to measure the in vivo intracellular levels of NAD+ and NADH at the relatively low magnetic field of 1.5 tesla (T). Our results show the feasibility of the in vivo determination of NAD+ and NADH from relatively small volumes of human tissues studied at 1.5 T. These results are clinically relevant as the currently available systems for human use mainly operate at 1.5 or 3.0.

Prospective Comparative Study Between Proximal Femoral Nail vs. Screw Augmented Proximal Femoral Nail in Unstable Intertrochanteric Fractures of Femur.

Introduction The proximal femoral nail (PFN) is a widely accepted fixation method for the management of unstable intertrochanteric fractures. Reconstructing the lateral trochanteric wall and ensuring the stability of the trochanteric fragments are considered to be essential for enhancing the prognosis of unstable intertrochanteric fractures. The aim of this study is to evaluate and compare the results of the management of unstable intertrochanteric fracture of the femur using PFN and the screw-augmented PFN (aPFN). Methods This prospective comparative study was undertaken from January 2020 to July 2021 and included 60 patients presenting with unstable intertrochanteric fractures (AO/OTA type 31-A2.2 and 31-A2.3) at a tertiary care teaching institute in northern India. The enrolled patients were randomly divided into two groups (group 1 and group 2) and were managed with screw-augmented PFN and PFN, respectively. Functional outcome was evaluated using the Salvati and Wilson score at the 12-month follow-up. SPSS version 24.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. A p-value less than 0.05 was regarded as significant. Results The average time to union of the fractures in group 1 was 12.66 ± 1.68 weeks, while it was 13.47 ± 1.47 weeks in group 2 (p = 0.055). At the 12-month follow-up, the average functional outcome, as evaluated by Salvati and Wilson score, was 34 ± 2.40 in group 1, whereas it was 31.58 ± 4.4 in group 2; and the difference was observed to be statistically significant (p = 0.011). Group 1 had 28 patients (93.33%) with excellent to good results, while group 2 had 25 patients (83.33%) with excellent to good results. One patient in group 1 and five patients in group 2 had poor outcomes at the 12-month follow-up. Conclusion Screw-augmented PFN has better functional outcomes as compared to PFN alone for the management of unstable intertrochanteric fractures. Hence, in our opinion, screw augmentation of PFN may be the better fixation technique for most unstable intertrochanteric femur fractures.

Reconstruction of Scalp with Local Axial Flaps.

The scalp is a unique part of the human body and various etiological factors, such as tumour extirpation, infection, burns, or trauma, can lead to scalp defects. Primary closure, skin grafting, local flaps, tissue expansion or free tissue transfer are modalities available for scalp reconstruction. In this article, the authors share their institutional experience using various local flaps concerning the size, location, depth of defect and the quality of surrounding tissue. From September 2017 to January 2020, 54 patients underwent scalp reconstruction with local flaps for a sizeable defect size of 5-150 cm2 in the Department of Plastic Surgery, SMS Medical College, Jaipur. Patients were identified by age, sex, cause of the scalp defect; the location, size, and depth of the defect; condition of surrounding tissue and the type of reconstruction done. The most common cause of scalp defect was excision of malignant tumour (50%). 30 patients had a large sized defect (40-90 cm2) and in 28 patients had 90-150 cm2 defects. Surgical reconstruction was done using local flaps, transposition flap was the most used in 36 patients (66.7%) followed by rotation advancement flap in 11 patients (20.4%). The recovery was relatively quick. Minor complications happened in 5 patients (9.3%) that were managed conservatively. In the present era of microsurgical reconstruction, local options as axial flaps provide a simpler and safer method of scalp reconstruction. A carefully planned scalp flap gives healthy, robust, hair-bearing tissue coverage and requires a shorter healing time for the patients.

The Effect of Heartfulness Meditation Program on Burnout and Satisfaction With Life Among Accounting Professionals.

Background: Accounting professionals experience a stressful working environment with previous studies demonstrating a high prevalence of burnout. Meditation-based interventions have a potential role in decreasing burnout and improving satisfaction with life. However, the benefits of Heartfulness meditation intervention have not been demonstrated among accounting professionals. Objective: To evaluate the effects of an 8-week Heartfulness Meditation program on burnout and satisfaction with life in chartered accountants. Methods: The study was a prospective cohort analysis comparing burnout and satisfaction with life outcomes among accounting professionals who either self-selected to participate in the Heartfulness Meditation Program (intervention group) or with no particular intervention (control group). Maslach Burnout Inventory (MBI) and Satisfaction with Life Scale (SWLS) scores were collected at baseline and at the end of the study period. Results: Two hundred and six participants completed the study. Participants in the intervention group (n = 107) experienced statistically significant improvement in MBI emotional exhaustion from 2.17 to 1.75 (P = .00) and overall MBI score decreased from 2.99 to 2.83 (P = .020). Participants in the control group (n = 99) experienced statistically significant improvement for emotional exhaustion only, from 1.82 to 1.52 (P = .009). Further, participants in the intervention group demonstrated statistically significant improvement with SWLS from 4.90 to 5.17 (P = .005). While participants in the intervention group experienced higher levels of decline (19.55%) compared to the control group (16.41%) for emotional exhaustion, it was not statistically significant. Conclusion: The current study is one of the first attempts of a Heartfulness meditation intervention to reduce burnout and improve satisfaction with life among accounting professionals. Both the intervention group and the control group showed an improvement of emotional exhaustion. The statistically significant improvements observed in the overall MBI and SWLS outcomes in the intervention group suggest an online Heartfulness meditation program could serve as a potential tool for reducing burnout and improving satisfaction among accounting professionals.

Laparoscopic Versus Open Ventral Hernia Repair: Experience at a Tertiary Care Center in Western Rajasthan.

Background Ventral hernias are the second most common type of hernias accounting for 21-35% of all hernia types. Ventral hernia includes incisional, umbilical, epigastric, and Spigelian hernias, among others. Currently, patients and surgeons prefer laparoscopic repair of ventral hernias. This study aimed to compare laparoscopic with open hernia repair in terms of various operative and patient parameters. Methodology This was a prospective observational study conducted in the Department of General Surgery, Dr. Sampurnanand Medical College, Jodhpur. All patients admitted with a diagnosis of ventral hernia for mesh repair (open as well as laparoscopic) were included. Laparoscopic and open hernia repair were compared in terms of operative time, postoperative hospital stay, time to resume routine activity, postoperative complications, and recurrence. Results Among the 50 patients included in the study (25 patients each in the laparoscopic and open groups), the mean operative time was 57.52 ± 5.80 minutes in the laparoscopic group and 59.8 ± 11.15 minutes in the open group. The mean hospital stay in the laparoscopy and open groups was 7.4 ± 1.58 days and 9.88 ± 2.96 days, respectively (p-value = 0.0006; significant). Postoperative pain (using the visual analog scale score) was less in patients who underwent laparoscopic surgery (p-value = 0.001; significant). Seroma and surgical site infections were the most common complications which were observed more in the open hernia repair group. Recurrence was seen in one case operated by the open technique. Conclusions Laparoscopic ventral hernia repair is technically safer, effective, and feasible with better clinical outcomes in patients seeking treatment in a government hospital.

Adaptation and Validation of the Malay Version of the Stress and Anxiety to Viral Epidemics-6 Items Scale Among the General Population.

The coronavirus disease pandemic has caused untold distress owing to both its physical and psychological sequelae, and such distress is further exacerbated by multiple socioeconomic ramifications. The Stress and Anxiety to Viral Epidemics-6 Items (SAVE-6). Scale was developed to specifically assess the anxiety response of the general population to viral epidemics. This study aimed to establish the psychometric properties of the Malay version of the SAVE-6 Scale in the general population. Herein, a total of 257 individuals participated. World Health Organization instrument validation protocols were used to translate and back-translate the Malay SAVE-6 Scale. Subsequently, the classical test theory and Rasch analysis were used to ascertain the validity and reliability of the scale. Cronbach α was used to measure the internal consistency, which was found to be satisfactory (α = 0.866). The correlations between the SAVE-6 Scale and other scales, including the Generalized Anxiety Disorder-7 Items Scale (r = 0.421, p < 0.001) and Patient Health Questionnaire-9 Items (r = 0.354, p < 0.001) were significant. Taken together, the Malay version of the SAVE-6 Scale is valid and reliable for use in the general population and is psychometrically suitable for assessing stress and anxiety specific to viral epidemics.

Carotid Endarterectomy and Carotid Artery Stenting for Symptomatic Carotid Stenosis: An Experience of a Hybrid Neurosurgeon in a Developing Nation.

Background: Stenosis of the ICA is an important cause of ischemic stroke and associated morbidity and mortality. Carotid artery stenting (CAS) and carotid endarterectomy (CEA) help to prevent impending or subsequent ischemic stroke in such patients. Aim and Objective: To study the outcome and adverse events associated with CEA and CAS. To determine the generalization of results obtained with multicentric trials such as CREST, etc., by comparing the results obtained by a single neurosurgeon in a community setting. Material and Methods: From Jan 2014-Dec 2017, 80 patients presented with symptomatic carotid stenosis. Out of these 80 patients, 65 underwent intervention; 34 patients underwent CEA and 31 patients underwent CAS. Pre-defined variables like age, sex, and degree of stenosis were assessed as potential risk factors, and the patients' clinical features, radiological imaging, and procedural complications were documented. Results: The primary outcome of procedure-related stroke, major adverse events (MAEs), and death at 30 days follow-up and long-term outcomes of restenosis at 1 year were analyzed. Peri-procedural stroke occurred in 2 cases (6.4%) of CAS; one suffered an ischemic stroke and other suffered a hemorrhagic stroke. Three cases of CEA suffered procedure-related events; one (2.9%) suffered TIA while the other two developed postoperative local hematoma without neurological deficit; one was treated conservatively while the other required re-exploration due to pressure symptoms. Restenosis occurred in one case that underwent CAS. Conclusion: CAS and CEA are complementary approaches in treating symptomatic carotid stenosis even when performed by a single hybrid neurosurgeon as results obtained are commensurable to major studies like CREST.

Perforator propeller flaps for lower extremity soft-tissue defect reconstruction: Shortening the learning curve.

Background: The perforator propeller flap is an advantageous option for soft tissue reconstruction in the lower limb as it ensures the preservation of the main artery and muscle, eliminates the need for microsurgical reconstruction as well as provides "like with like" resurfacing of the defects. Despite this, it remains a technically demanding reconstructive option for residents and surgeons with little experience in perforator dissection. We aimed to evaluate the clinical outcomes of our patients whose soft tissue defects were addressed with propeller flaps. Methods: A retrospective study of all propeller flap based reconstruction done on patients with soft tissue defects involving the distal third of the leg was undertaken from August 2018 to December 2020. Results: 28 patients were treated with propeller flaps for various lower extremity defects. The median defect size was 12 cm2. The posterior tibial artery (PTA) was used in eleven cases (39.3%) and the peroneal artery (PA) in seventeen of the cases (60.7%). The complication rate was 28.6% (n = 8). The complete flap necrosis rate was 10.7% (n = 3) and partial flap necrosis rate was 7.1% (n = 2), The rate of venous congestion was 7.1% (n = 2) and wound dehiscence occurred in 3.5% (n = 1). There was a significant negative correlation between the number of cases performed by a resident and the operative time. Conclusion: Although propeller flaps are a reliable option to address lower extremity defects, they have a long learning curve and require a good amount of experience and perforator dissection skills to reduce the probability of flap failure. We are of the opinion that residents should be adequately trained in this procedure to ensure optimal outcome delivery.

Hepatobiliary malformations: proposed updation of classification system, clinicopathological profile and a report of largest pediatric giant choledochal cyst.

BACKGROUND: The present study was aimed to update the classification of hepatobiliary malformations and study the clinicopathological profile of pediatric choledochal cyst (CDC) and pediatric giant choledochal cyst (GCC) patients undergone surgery. METHODS: We have retrospectively analysed the data of 57 consecutive cases of CDCs in paediatric patients from a time period spanning from 2016 to 2020. RESULTS: Revised classification of hepatobiliary malformations was proposed and these were divided into 2 broad headings, choledochal (congenital and acquired) and extra-choledochal spectrum. 57 pediatric patients were diagnosed as having CDC with average age 4.615 years and female to male ratio of 3.7:1. We have also reported one of the largest GCC measuring 23 × 10 × 9 cm size. The classical triad was known to be more common and seen in 60% GCCs as opposed to 14.5% in CDCs. Values of serum bilirubin, SGOT, SGPT, PT/INR were elevated in CDC series and normal in GCC patients. 55 patients (96.5%) underwent cyst excision and Roux-en-Y hepaticojejunostomy. Mortality was seen in 7.01% patients (n = 4) following surgery. CONCLUSION: Simplified and broader classification system for CDCs has been proposed. Clinical studies found that GCC differs considerably from classical CDCs.

Advanced magnetic resonance imaging and spectroscopy in a case of neurocysticercosis from North America.

Neurocysticercosis (NCC) is a parasitic infection caused by Cysticercus cellulosae, the metacestode of pork tapeworm (Taenia solium). NCC is one of the most common public health problems worldwide. We present a patient harboring a bilobed ring-enhancing lesion with a presumed diagnosis of brain metastasis, who returned to the USA after traveling to an endemic region. The diagnosis of NCC was established based on a characteristic resonance of succinate on proton magnetic resonance spectroscopy. Also, higher mean diffusivity and lower fractional anisotropy along with relative cerebral blood volume were observed from the lesion compared to contralateral normal brain regions. Multiparametric analysis may improve the differential diagnosis of ring-enhancing intracranial lesions such as NCC.