Concentration of clarified pool by single-pass tangential flow filtration to improve productivity of protein A capture step: Impact of clarification strategies.

Protein A capture chromatography remains a high-cost and relatively low-productivity step for downstream processing of monoclonal antibodies. As bioprocessing transitions toward intensified processes, maximizing the efficiency of individual steps is key to achieving economic targets. This study was performed to assess the impact of inline concentration of clarified cell culture fluid (CCF), using single-pass tangential flow filtration, on protein A chromatography purification productivity. CCF with varying levels of impurities and turbidity were obtained dependent upon the clarification method. These CCFs were concentrated and processed over a protein A capture step. Productivity increases of 1.8- to 2.6-fold were achieved as compared to a protein A capture step with no CCF concentration. Achieving such targeted improvements requires careful consideration of the multiple components in the clarification strategy before implementation.

Perception of telemedicine among orthopedic surgeons and patients and an analysis of the factors governing its overall efficacy: Results from the COVID-19 pandemic.

Background: Providing health-care services through telemedicine for musculoskeletal ailments after the first wave of COVID-19 may help reduce the burden on the already-strained health-care system. Objectives: The objectives of this study were (1) to assess the satisfaction levels of orthopedic surgeons and patients with respect to telemedicine and (2) to determine the factors governing the overall efficacy of telemedicine consultations. Materials and Methods: A cross-sectional study was conducted to ascertain the perception of telemedicine (both doctors and patients) under the following domains - (1) information provided and ease of usage; (2) doctor-patient communication; (3) ease of prescribing and understanding treatment; and (4) audio-video quality of the consultation. The influence of these factors on overall satisfaction was determined using multinomial logistic regression analysis. Results: Of the 204 patients and 27 surgeons who completed the questionnaire, 77% (patients) and 89% (surgeons) were satisfied with the overall efficacy of telemedicine. Maximum satisfaction was noted with the ease of obtaining a telemedicine appointment (168/204). 68.6% of patients further stated they would prefer future visits virtually. While all four factors were found to have a significant correlation (P < 0.001) with the overall efficacy of teleconsultation services, the quality of the telephone call (odds ratio [OR] =90.15) and good doctor-patient communication (OR = 15.5) were found to be the most important of the lot. Conclusion: Our study not only demonstrates the high degree of satisfaction with telehealth services but is also able to pinpoint the areas where improvement is needed to enhance the overall experience with this technology.

Comparative and clinical evaluation between piezoelectric and conventional rotary techniques for mandibular impacted third molar extraction.

Purpose: The aim of this study was to evaluate and compare the operative and postoperative outcomes of the mandibular impacted third molar removal using piezoelectric technique and conventional rotary bur technique. Settings: The study was conducted in the department of oral and maxillofacial surgery between January 1, 2019, and January 1, 2020. Materials and Methods: Thirty patients, with an age of 18-40 years, with asymptomatic bilateral impacted mandibular third molars, were selected for the study and randomly surgical extraction was done either using piezoelectric or the conventional rotary bur technique on each site. The intraoperative time taken, postoperative pain, swelling, and trismus were assessed over a follow-up period of 7 days postoperatively. Results: Study and control groups were compared using paired t-test. There was statistical significance in reduction of pain and swelling in the study group where the duration of surgery was increased in the study group. Conclusion: Even if piezoelectric technique takes more time but can be used safely as another technique to conventional surgical method with surgical bur and handpiece for removal of impacted mandibular third molars.

Improved endotoxin removal using ecofriendly detergents for intensified plasmid capture.

Increasing plasmid demand for both production of viral and gene therapies as well as nucleic acid based vaccines has highlighted bottlenecks in production. One bottleneck is traditional bead-based chromatography as a capture step. To meet the needs of fast-growing markets, new production solutions are needed. These solutions must enable efficient capture of a diverse range of plasmid types and excellent clearance of bacterial host impurities, such as endotoxin. Enhanced endotoxin clearance during chromatographic purification has previously been demonstrated with detergents such as Triton™ X-100. However, degradation products of Triton™ X-100 are known to have a negative environmental impact, and more sustainable, environmentally benign alternatives have been identified. This work establishes an efficient, intensified plasmid capture using convective anion exchange (AEX) chromatography. The feasibility of the intensified capture approach was assessed with different membrane and a monolith AEX supports. Various detergents from different physico-chemical classes were evaluated with different AEX technologies. Purification efficiency evaluated endotoxin and host cell protein (HCP) clearance, plasmid yield, potential interference of the detergents with analytical in-process control assays, and overall process compatibility. This comprehensive screening approach provides valuable insights to intensified plasmid production.

Ten-Segment Classification has Lowest Inter/Intra-Observer Reliability as Compared to Schatzker, Three-Column and AO Systems for Tibial Plateau Fractures: A Comparison Based on Surgeons' Experience.

Objectives: The primary aim of this study was to assess the reliability of the ten-segment classification system proposed (TSC) by Krause et al. and see how it compares with the traditionally used Schatzker classification, AO classification system, and Luo's "Three columns" classification (ThCC) system. The second aim of this study was to assess the inter-observer reliability of the above classifications based on professional experience by comparing the entry level of residents (1 year into postgraduation), senior residents (1 year after postgraduation completion), and faculty (>10 years after postgraduation completion). Methods: 50 TPFs were classified by a 10-segment classification system, and its intra-observer (at 1-month interval) and inter-observer reproducibility was checked using k values by three different groups with varying levels of experience (Group I, II, and III comprised of 2 juniors residents, senior residents and consultants each), and the same was compared for three other common classification systems (Schatzker, AO and 3 -column). Results: 10-segment classification showed least k for both inter-observer (0.08) and intra-observer (0.03) reliability. Highest individual inter-observer (k= 0.52) and intra-observer reliability (k= 0.31) was for Schatzker classification in Group I. Lowest individual inter-observer and intra-observer reliability was seen for 10-segment classification (k= 0.07) and AO classification system (k= -0.03) respectively. Conclusion: 10-segment classification showed the lowest k for both inter-observer and intra-observer reliability. The inter-observer reliability for the Schatzker, AO, and 3- column classifications reduced with increasing experience of the observer (JR>SR>Consultant). A possible reason could be a more critical evaluation of the fractures with increasing seniority.

Corona Mortise- anatomical variants and implications in pelvic-acetabular surgery: An evidence based review.

Background: Corona Mortise is the name given to the anastomotic vessels forming a communication between external and internal iliac vascular systems. These channels have a high tendency to cause uncontrollable bleeding if injured and are particularly at risk during the anterior approach to acetabulum. While previous studies have described them as arterial or venous connections or both, there is still a lack of consensus regarding exact nature and location of these vessels, which make their timely identification all the more challenging. Objective: The present review is aimed at performing a comprehensive review of existing literature and discuss the anatomy and implications of correct identification of Corona Mortise in pelvic-acetabular surgery. Conclusion: Corona Mortise is more commonly venous than arterial. This not only makes haemorrhage control more challenging but also precludes the use of pre-operative angiography. However, most authors do not recommend a change in surgical approach for fear of damaging these vessels.

Curettage versus wide resection followed by arthrodesis/arthroplasty for distal radius Giant cell tumours: A meta-analysis of treatment and reconstruction methods.

Purpose: Primary aim of this review was to compare the two treatment modalities-curettage and wide excision (WE)- of Giant cell tumours of distal radius along with the methods of reconstruction viz. arthrodesis (AD) and arthroplasty (AP), and determine which had a better outcome. Methods: PubMed and Cochrane library databases were systematically searched using a well-defined search strategy by two independent reviewers. Inclusion/exclusion criteria were predetermined using the PICO format. MINORS tool was used to evaluate study quality. Recurrence rate (RR) was the chief oncological determinant whereas range of motion, grip strength, disability of arm, shoulder and hand (DASH) and musculoskeletal tumour society (MSTS) scores and complication rates were the functional outcome measures used. Results: For the first part, a total of 11 articles (284 patients) were analysed. The second half- AP versus AD-included four studies (71 patients). Quantitative analysis revealed a significantly higher RR (Odds ratio (OR) 8.6 [95% CI, 3.4, 21.75]) with curettage. WE, on the other hand, was associated with a higher complication rate (OR 0.3[ 95% CI, 0.14, 0.62]) and lower grip strength (Standard Mean Difference (SMD) 18.08[95% CI, 13.78, 22.37]). Complication rates were also significantly higher with wrist AP (OR 6.36[ 95% CI, 1.72, 23.52]). Remaining functional parameters failed to show any significant difference between either group. Conclusion: WE is the preferred surgical strategy in terms of lower RR and functionally equivalent results. In terms of the choice of reconstruction following WE, there is a trend towards higher patient satisfaction after wrist AD.

Identification of vaccine targets & design of vaccine against SARS-CoV-2 coronavirus using computational and deep learning-based approaches.

An unusual pneumonia infection, named COVID-19, was reported on December 2019 in China. It was reported to be caused by a novel coronavirus which has infected approximately 220 million people worldwide with a death toll of 4.5 million as of September 2021. This study is focused on finding potential vaccine candidates and designing an in-silico subunit multi-epitope vaccine candidates using a unique computational pipeline, integrating reverse vaccinology, molecular docking and simulation methods. A protein named spike protein of SARS-CoV-2 with the GenBank ID QHD43416.1 was shortlisted as a potential vaccine candidate and was examined for presence of B-cell and T-cell epitopes. We also investigated antigenicity and interaction with distinct polymorphic alleles of the epitopes. High ranking epitopes such as DLCFTNVY (B cell epitope), KIADYNKL (MHC Class-I) and VKNKCVNFN (MHC class-II) were shortlisted for subsequent analysis. Digestion analysis verified the safety and stability of the shortlisted peptides. Docking study reported a strong binding of proposed peptides with HLA-A*02 and HLA-B7 alleles. We used standard methods to construct vaccine model and this construct was evaluated further for its antigenicity, physicochemical properties, 2D and 3D structure prediction and validation. Further, molecular docking followed by molecular dynamics simulation was performed to evaluate the binding affinity and stability of TLR-4 and vaccine complex. Finally, the vaccine construct was reverse transcribed and adapted for E. coli strain K 12 prior to the insertion within the pET-28-a (+) vector for determining translational and microbial expression followed by conservancy analysis. Also, six multi-epitope subunit vaccines were constructed using different strategies containing immunogenic epitopes, appropriate adjuvants and linker sequences. We propose that our vaccine constructs can be used for downstream investigations using in-vitro and in-vivo studies to design effective and safe vaccine against different strains of COVID-19.

Advancement in Deep Learning Methods for Diagnosis and Prognosis of Cervical Cancer.

Cervical cancer is the leading cause of death in women, mainly in developing countries, including India. Recent advancements in technologies could allow for more rapid, cost-effective, and sensitive screening and treatment measures for cervical cancer. To this end, deep learning-based methods have received importance for classifying cervical cancer patients into different risk groups. Furthermore, deep learning models are now available to study the progression and treatment of cancerous cervical conditions. Undoubtedly, deep learning methods can enhance our knowledge toward a better understanding of cervical cancer progression. However, it is essential to thoroughly validate the deep learning-based models before they can be implicated in everyday clinical practice. This work reviews recent development in deep learning approaches employed in cervical cancer diagnosis and prognosis. Further, we provide an overview of recent methods and databases leveraging these new approaches for cervical cancer risk prediction and patient outcomes. Finally, we conclude the state-of-the-art approaches for future research opportunities in this domain.

Health-Care Utilization and Outcomes with 10 kHz Spinal Cord Stimulation for Chronic Refractory Pain.

BACKGROUND: Chronic pain is a common condition associated with decreased quality of life and increased health-care costs. Opioid analgesics are routinely used to treat chronic pain despite limited evidence of long-term efficacy. Spinal cord stimulation at a frequency of 10 kilohertz (10kHz-SCS) has been shown to be effective for treating chronic pain. OBJECTIVE: This study was conducted to evaluate the effects of 10kHz-SCS on patients' pain intensity, volume of pain interventions, and opioid intake in a real-world setting. STUDY DESIGN: This study was a retrospective review of patient data. SETTING: The study was conducted at a single, community-based clinic. METHODS: Outcomes including pain relief, quality of life, opioid intake, and rate of health-care usage were evaluated using data from patients who were implanted with a 10kHz-SCS device to treat chronic pain. These outcomes were then compared for the pre- and post-implant periods. RESULTS: A total of 47 patients with a mean follow-up duration of 15.6 ± 6.2 months were included in this analysis. Mean pain relief was 73 ± 22% and 89% were responders at the final follow-up visit. The rate of medical interventions fell from 3.48±3.05 per year before starting 10kHz-SCS to 0.49±1.16 per year afterward (P < 0.001). Of 30 patients with available opioid consumption data, 89% maintained or decreased their intake after implant. CONCLUSION: Retrospective data from a single center, with minimal exclusion criteria shows clinically significant pain relief with 10kHz-SCS, accompanied by significant indirect benefits including stable or reduced opioid use and reduced interventional procedures.

MCA-DN: Multi-path convolution leveraged attention deep network for salvageable tissue detection in ischemic stroke from multi-parametric MRI.

BACKGROUND AND OBJECTIVE: Accurate and timely treatment of ischemic stroke can restore the blood flow in the affected area and reduce the risk of disability and death. Identification and localisation of both direct and collateral blood flow restriction from MRI using computational intelligence play a crucial role in assisting manual diagnosis decisions in stroke treatment. METHOD: A novel multi-path convolution leveraged attention based deep network (MCA-DN) is proposed to address this challenge. MCA-DN combines multi-path convolution derived attention making different weighted filters in each attention convolution sub-path, with interactions on the same level of abstraction. This facilitates the network to focus on voxels with enhanced weighted activations, directing to a plausible lesion. Such a proposition of acquiring attention by embedding multiple filter paths, also prioritizes the selective activation of multi-parametric MRI sequences. The multi-path convolution assisted attention block allows the network layers to gain more insights on the input tensor, enabling the expansion of hypothesis search space with a controlled parameter count. RESULTS: The algorithm is evaluated on 139 patients of 3 datasets with 4 sub-datasets, including 2 benchmarked challenge datasets of ISLES-2015, 2017. MCA-DN achieved parametric measures of Dice similarity coefficient: 77.3 %, sensitivity: 82.8 %, and specificity: 98.8 %, for stroke segmentation, outperforming the five state-of-the-art methods in the field with encouraging success. CONCLUSION: Competitive performance of the MCA-DN demonstrates immense potential to assist patient-specific stroke treatment planning by estimating the benefit of reperfusion.

Acute Kidney Injury Secondary to Rhabdomyolysis: A Rare Complication of Low-Energy Trauma.

INTRODUCTION: Crush syndrome refers to the systemic manifestation of muscle cell injury following release of myocyte contents into the blood circulation. It is seen most commonly in patients sustaining high-energy trauma. Acute kidney injury is one of the most serious complications of crush syndrome and is an important cause of mortality in these patients. In contrast, the occurrence of rhabdomyolysis in patients sustaining low-energy trauma is sparsely reported in the literature. The authors report one such rare case. CASE REPORT: The patient was a 77-year-old hypertensive male who presented to the emergency following an episode of slip and fall at home. After prompt resuscitation, he was sent for radiological evaluation which revealed fractures of the left inter-trochanteric femur and left proximal humerus. Meanwhile, laboratory investigations showed grossly deranged renal parameters, along with elevated serum creatinine phosphokinase levels (more than 5 times the baseline). A diagnosis of acute kidney injury secondary to traumatic rhabdomyolysis was made. Medical management included adequate intravenous fluid administration combined with strict input-output monitoring. Subsequently, the patient underwent closed reduction and internal fixation of the inter-trochanteric femur fracture with a proximal femoral nail. However, fracture of the proximal humerus was managed non-operatively with sling immobilization as patient refused to give consent for a second surgery. CONCLUSION: Although rare, acute kidney injury secondary to rhabdomyolysis can occur in patients with low-energy trauma. It is important not to confuse it with chronic renal insufficiency, especially in geriatrics many of whom are long-standing hypertensives.

Primary aneurysmal bone cyst of the calcaneum: A report of three cases and review of literature.

CASE DESCRIPTION: Aneurysmal bone cysts (ABCs) are locally aggressive, cystic lesions of the skeletal system, most commonly seen in the metaphyseal region of long bones. On the other hand, an ABC of the foot (especially the calcaneum) is a rare entity, with very few cases reported in the literature. In this study, we present three such cases who presented to us with the chief complaint of chronic heel pain. All three patients were clinically reviewed following which a comprehensive radiological workup was performed. The latter revealed a solitary, expansile lesion within the calcaneum in all them. Treatment included extended curettage and reconstruction using autologous iliac crest bone grafts. Histopathological analysis of the curetted sample was consistent with features of primary ABC. There were no complications and all lesions had re-ossified at the latest follow up. CONCLUSION: Calcaneal ABCs are rare, atypical lesions warranting a high index of suspicion and correlation of the patient's clinical, radiological and histopathological features to make a correct diagnosis.

Arthroscopic Subtalar Arthrodesis as a Treatment Strategy for Subtalar Arthritis: A Systematic Review.

Arthroscopic subtalar arthrodesis is a relatively new technique which is increasingly being used by foot and ankle surgeons as an alternative to open surgery. However, there is still a lack of consensus with respect to the efficacy of the procedure. The purpose of this review was to ascertain (1) whether arthroscopic subtalar arthrodesis improves the functional outcome of treated patients and (2) how do the 2 techniques of subtalar arthroscopy (posterior and lateral) compare with each other. MEDLINE and Cochrane Library databases were accessed by 2 independent reviewers. Inclusion/exclusion criteria were predefined. National Institute of Health risk of bias assessment tool was used to determine the methodological quality of the included studies. A total of ten studies with 234 patients (240 feet) were included. The most common indication for arthroscopic subtalar fusion was posttraumatic subtalar arthritis. Weighted pre- and postoperative American Orthopaedic Foot and Ankle Society scores were 47 and 80.7, respectively. Average time to fusion was 10.2 weeks and weighted mean fusion rate was 95%. Pain secondary to prominent hardware and nonunion were the most common complications. Although improvement in functional scores was higher and complication rate lower with the posterior group, a better fusion rate was seen with the lateral approach. Arthroscopic fusion techniques have shown to be an effective alternative to open surgery. While there was a trend for better functional outcome with the posterior approach, randomized control trials comparing the 2 techniques are needed to better assess their respective outcomes.

Quantitative analysis of brain herniation from non-contrast CT images using deep learning.

BACKGROUND: Brain herniation is one of the fatal outcomes of increased intracranial pressure (ICP). It is caused due to the presence of hematoma or tumor mass in the brain. Ideal midline (iML) divides the healthy brain into two (right and left) nearly equal hemispheres. In the presence of hematoma, the midline tends to shift from its original position to the contralateral side of the mass and thus develops a deformed midline (dML). NEW METHOD: In this study, a convolutional neural network (CNN) was used to predict the deformed left and right hemispheres. The proposed algorithm was validated with non-contrast computed tomography (NCCT) of (n = 45) subjects with two types of brain hemorrhages - epidural hemorrhage (EDH): (n = 5) and intra-parenchymal hemorrhage (IPH): (n = 40)). RESULTS: The method demonstrated excellent potential in automatically predicting MLS with the average errors of 1.29 mm by location, 66.4 mm2 by 2D area, and 253.73 mm3 by 3D volume. Estimated MLS could be well correlated with other clinical markers including hematoma volume - R2 = 0.86 (EDH); 0.48 (IPH) and a Radiologist-defined severity score (RSS) - R2 = 0.62 (EDH); 0.57 (IPH). RSS was found to be even better correlated (R2 = 0.98 (EDH); 0.70 (IPH)), hence better predictable by a joint correlation between hematoma volume, midline pixel- or voxel-shift, and minimum distance of (ideal or deformed) midline from the hematoma (boundary or centroid). CONCLUSION: All these predictors were computed automatically, which highlighted the excellent clinical potential of the proposed automated method in midline shift (MLS) estimation and severity prediction in hematoma decision support systems.

Complete paraplegia with diffuse osteolytic skeletal metastases: an uncommon presentation of carcinoma of the prostate.

INTRODUCTION: Skeletal metastases of advanced prostatic cancer are usually osteoblastic in appearance. Osteolytic secondaries are an uncommon entity. In such scenarios, it is important to differentiate prostatic metastases from other pathologies which give an identical radiological appearance, such as multiple myeloma. Another important point to remember is that neurological complications secondary to prostatic metastases are quite uncommon. CASE PRESENTATION: We describe a man with advanced prostatic carcinoma who presented to us with an uncommon combination of sudden onset complete paraplegia associated with diminished sensation in the lower half of the body and diffuse osteolytic lesions in the entire skeletal system. On detailed workup, it was found that his prostatic specific antigen (PSA) was grossly elevated. Markers for multiple myeloma were negative. Accordingly, computerized tomography of the abdomen was performed. The latter revealed an enlarged prostate gland infiltrating into the bladder base. Histopathological analysis from the prostate as well as the bone marrow showed an identical picture thereby confirming our diagnosis. The individual underwent palliative spinal canal decompression following which he was put on anti-androgenic treatment. At one year follow up, he was ambulatory and able to walk with use of crutches. DISCUSSION: To the best of our knowledge, this is the first reported case of osteolytic prostatic metastases presenting as complete paraplegia. In this situation, in addition to evaluation for prostate CA, we also recommend screening for multiple myeloma as the clinico-radiological profile of the two diseases are similar but their management is very different.