Non-surgical correction of knee flexion deformity in persons with haemophilia: A staged multidisciplinary approach.

INTRODUCTION: Flexion deformity of the knee is a common complication following recurrent haemarthrosis in persons with haemophilia (PWH) on episodic factor replacement therapy, restricting independent mobility. There is limited literature on the comprehensive management of this condition. This report provides the outcome of a staged multidisciplinary approach for the correction of knee flexion deformity (KFD) even in limited resource settings. PATIENTS AND METHODS: The data of 49 consecutive PWH who were treated for KFD were analysed. The approach included graded physical therapy (PT), followed by serial casting and/or mobilisation under anaesthesia (MUA). MUA was done in carefully selected knees. Surgical correction was opted when non-surgical methods failed. RESULTS: Of the 49 patients (55 knees), with a median KFD of 40 degrees (range: 10-90), 26/55 (47%) were corrected by graded PT. With serial casting, 9/19 (47%) knees had their KFD corrected. MUA was done for 11 knees of which five achieved correction (45%). Surgical correction was required for only seven knees (12.7%). Following this approach, KFD improved from 40 degrees (range: 10-90) to 15 degrees (range: 0-40), with only minor loss of flexion from 105 (range: 60-155) to 90 degrees (range: 30-150). Out of 55 KFD, 46 (83.6%) KFD were corrected; non-surgical, 39 (70.9%) and surgery, seven (12.7%). The remaining patients (nine KFD; 16.4%) were able to achieve their functional goal despite not meeting the correction criteria. CONCLUSION: This study shows that in PWH, functionally significant KFD correction can be achieved in about 71%, through non-surgical methods, even without prophylactic factor replacement.

Adaptive designs in clinical trials: a systematic review-part I.

BACKGROUND: Adaptive designs (ADs) are intended to make clinical trials more flexible, offering efficiency and potentially cost-saving benefits. Despite a large number of statistical methods in the literature on different adaptations to trials, the characteristics, advantages and limitations of such designs remain unfamiliar to large parts of the clinical and research community. This systematic review provides an overview of the use of ADs in published clinical trials (Part I). A follow-up (Part II) will compare the application of AD in trials in adult and pediatric studies, to provide real-world examples and recommendations for the child health community. METHODS: Published studies from 2010 to April 2020 were searched in the following databases: MEDLINE (Ovid), Embase (Ovid), and International Pharmaceutical Abstracts (Ovid). Clinical trial protocols, reports, and a secondary analyses using AD were included. We excluded trial registrations and interventions other than drugs or vaccines to align with regulatory guidance. Data from the published literature on study characteristics, types of adaptations, statistical analysis, stopping boundaries, logistical challenges, operational considerations and ethical considerations were extracted and summarized herein. RESULTS: Out of 23,886 retrieved studies, 317 publications of adaptive trials, 267 (84.2%) trial reports, and 50 (15.8%) study protocols), were included. The most frequent disease was oncology (168/317, 53%). Most trials included only adult participants (265, 83.9%),16 trials (5.4%) were limited to only children and 28 (8.9%) were for both children and adults, 8 trials did not report the ages of the included populations. Some studies reported using more than one adaptation (there were 390 reported adaptations in 317 clinical trial reports). Most trials were early in drug development (phase I, II (276/317, 87%). Dose-finding designs were used in the highest proportion of the included trials (121/317, 38.2 %). Adaptive randomization (53/317, 16.7%), with drop-the-losers (or pick-the-winner) designs specifically reported in 29 trials (9.1%) and seamless phase 2-3 design was reported in 27 trials (8.5%). Continual reassessment methods (60/317, 18.9%) and group sequential design (47/317, 14.8%) were also reported. Approximately two-thirds of trials used frequentist statistical methods (203/309, 64%), while Bayesian methods were reported in 24% (75/309) of included trials. CONCLUSION: This review provides a comprehensive report of methodological features in adaptive clinical trials reported between 2010 and 2020. Adaptation details were not uniformly reported, creating limitations in interpretation and generalizability. Nevertheless, implementation of existing reporting guidelines on ADs and the development of novel educational strategies that address the scientific, operational challenges and ethical considerations can help in the clinical trial community to decide on when and how to implement ADs in clinical trials. STUDY PROTOCOL REGISTRATION: https://doi.org/10.1186/s13063-018-2934-7 .

Cannabinoids for symptom management in children with cancer: A systematic review and meta-analysis.

BACKGROUND: Despite the widespread use of medical cannabis, little is known regarding the safety, efficacy, and dosing of cannabis products in children with cancer. The objective of this study was to systematically appraise the existing published literature for the use of cannabis products in children with cancer. METHODS: This systematic review, registered with the International Prospective Register of Systematic Reviews (CRD42020187433), searched four databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library. Abstracts and full texts were screened in duplicate. Data on types of cannabis products, doses, formulations, frequencies, routes of administration, indications, and clinical and demographic details as well as reported efficacy outcomes were extracted. Data on cannabinoid-related adverse events were also summarized. RESULTS: Out of 34,611 identified citations, 19 unique studies with a total of 1927 participants with cancer were included: eight retrospective chart reviews, seven randomized controlled trials, two open-label studies, and two case reports. The included studies reported the use of various cannabis products for the management of symptoms. Cannabinoids were commonly used for the management of chemotherapy-induced nausea and vomiting (11 of 19 [58%]). In controlled studies, somnolence, dizziness, dry mouth, and withdrawal due to adverse events were more commonly associated with the use of cannabinoids. Across all included studies, no serious cannabis-related adverse events were reported. CONCLUSIONS: Although there is evidence to support the use of cannabis for symptom management, in children with cancer, there is a lack of rigorous evidence to inform the dosing, safety, and efficacy of cannabinoids. Because of the increasing interest in using cannabis, there is an urgent need for more research on medical cannabis in children with cancer.

Foot and Ankle Giant Cell Tumors Are Not so Aggressive After All: A Retrospective Study.

Giant cell tumors are most commonly seen around the knee and rarely around the foot and ankle. Therefore there is a paucity of data regarding the options of surgery, outcomes and recurrence of Giant cell tumors involving the foot and ankle. We retrospectively studied patients with Giant cell tumors of the foot and ankle from January 2009 to December 2017. We identified 19 (N = 19) patients with a minimum of 1-year follow-up. Their data was retrieved from the electronic database and analyzed. The mean follow-up period was 36.2 (range 12-96) months. On an average, the patients underwent 1.6 surgeries. The surgeries performed were extended curettage and bone graft/cement in 8 (42.1%) patients, excision and bone graft in 8 (42.1%) patients and excision and mega prosthesis in 3 (15.79%) patients. The most common complication was wound infection seen in 3 (15.79%) patients. None of the patients who underwent index procedure in our center (biopsy and surgery) had local recurrence. There were 9 (47.36%) patients with primary procedure elsewhere - 7 of them had no recurrence after surgery in our center. One (5.26%) amputation was eventually performed due to complications and not as a primary surgery. At the final review, all 19 (100%) patients with >1 year follow up were in remission. Local recurrence and wound infection were exclusively found in patients who presented to us after invasive procedures done elsewhere. With good surgical clearance, the uncommon presentations of foot and ankle Giant cell tumors can be treated to attain complete remission.

Changing pattern of trauma during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic compelled the Indian government to enforce a complete nationwide lockdown on 24th March 2020. METHODS: This retrospective study was done to analyse the profile of trauma patients presenting to the emergency department (ED) from January to August 2020. Data from 69 days of lockdown and 83 days of pre-lockdown periods were used to calculate the 30-day incidence rates. RESULTS: During the 7-month study period, 5220 patients presented to our ED with trauma; 2296 in the prelockdown phase (83 days), 1205 during the lockdown phase (69 days), and 1719 during the postlockdown phase (92 days). There was a significant decrease (36.7%) in the 30-day incidence rate of trauma victims presenting to the ED during the lockdown phase (525) compared with the prelockdown phase (830). The 30-day incidence of road traffic accidents (RTA), fall from height, fall on level ground and other trauma decreased by 53.2%, 26%, 23.2% and 12.9%, respectively, while assault cases increased by 8.3% during the lockdown period as compared with the prelockdown period. During the lockdown period, the 30-day incidence of trauma victims with a positive blood alcohol content decreased by 39.6% with a significant drop in the strict lockdown month of April 2020. CONCLUSIONS: A significant reduction in the incidence rate of trauma victims, especially RTA and geriatric trauma was seen during the gruelling lockdown period of the COVID 19 pandemic.

A comprehensive evaluation of adaptive daily planning for cervical cancer HDR brachytherapy.

The purpose of this study was to evaluate adaptive daily planning for cervi-cal cancer patients who underwent high-dose-rate intracavitary brachytherapy (HDR-BT) using comprehensive interfractional organ motion measurements. This study included 22 cervical cancer patients who underwent 5 fractions of HDR-BT. Regions of interest (ROIs) including high-risk clinical tumor volume (HR-CTV) and organs at risk (OARs) were manually contoured on daily CT images. All patients were clinically treated with adaptive daily plans (ADP), which involved ROI delineation and dose optimization at each treatment fraction. Single treatment plans (SP) were retrospectively generated by applying the first treatment fraction's dwell times adjusted for decay and dwell positions of the applicator to subsequent treatment fractions. Various existing similarity metrics were calculated for the ROIs to quantify interfractional organ variations. A novel similarity (JRARM) score was established, which combined both volumetric overlap metrics (DSC, JSC, and RVD) and distance metrics (ASD, MSD, and RMSD). Linear regression was performed to determine a relationship between interfractional organ varia-tions of various similarity metrics and D2cc variations from both plans. Wilcoxon signed-rank tests were used to assess ADP and SP by comparing EQD2 D2cc (α/ß = 3) for OARs. For interfractional organ variations, the sigmoid demonstrated the greatest variations based on the JRARM, DSC, and RMSD metrics. Comparisons between paired ROIs showed differences in metrics at each treatment fraction. RVD, MSD, and RMSD were found to be significantly correlated to D2cc varia-tions for bladder and sigmoid. The comparison between plans found ADP provided lower EQD2 D2cc of OARs than SP. Specifically, the sigmoid demonstrated sta-tistically significant dose variations (p = 0.015). Substantial interfractional organ motion occurs during HDR-BT based on comprehensive measurements and may significantly affect D2cc of OARs. Adaptive daily planning provides improved dose sparing for OARs compared to single planning with the extent of sparing being different among OARs.

Alkaptonuria with Fracture Neck of Femur - A Case Report.

Introduction: Alkaptonuria is a rare autosomal recessive genetic disorder found in 2-5/million live births. It results in dark brown pigmentation of connective tissues including cartilage and joint capsule that can often lead to arthropathy of large joints. However, bone fractures are unusual. This article describes a fracture neck of the femur in a patient with undiagnosed alkaptonuria managed at a rural center. Case Report: A 60-year-old daily wage laborer with previously pain-free hips presented with sudden onset pain in the left hip while walking with no prior history of trauma. Radiographs showed a displaced fracture of the neck of the left femur. She underwent Left hip hemiarthroplasty. Intraoperatively, her soft-tissue including the joint capsule and the femoral head had dark brown pigmentation. Postoperatively, her urine was tested and the same turned black supporting the clinical diagnosis of alkaptonuria. At her 1-year follow-up, she had a painless, stable, and mobile hip. Conclusion: We report a rare and unique case of neck of femur fracture in a patient with alkaptonuria treated with hemiarthroplasty in a resource-limited hospital in rural India. It is essential to consider the possibility of this condition when we come across a patient with an atypical fracture presentation. This article also presents an overview of alkaptonuria with a discussion on etiopathogenesis, clinical presentation, diagnosis, and management.

Grade 3 Proximal Humerus Giant Cell Tumour: Is Resection and Reconstruction with Prosthesis a Valuable Option?

Grade 3 proximal humerus giant cell tumours are uncommon and the results of their surgical management with prosthetic replacement are not well established. We retrospectively studied patients with grade 3 giant cell tumours of proximal humerus treated with excision and prosthetic replacement from January 2009 and December 2018. We identified 13 patients who underwent tumour excision and prosthetic replacement. There were 7 (53.8%) men and 6 (46.2%) women. The mean age at diagnosis was 30.4 years (range 16-48 years). The mean follow-up period was 72.2 months (range 24-132). Margins were positive in 4 (30.8%) patients, ≤ 1 mm in 8 (61.5%) patients, and negative in 1 (7.7%) patient. Local recurrence was seen in 2 (15.4%) patients. 1 out of 2 (50%) patients with local recurrence had pathological fracture at presentation and margins were positive in both (100%) patients. There were 3 (23.1%) complications-1 patient with joint subluxation, 1 patient with fracture post trauma, and 1 patient with surgical site infection. The mean overall Musculoskeletal Tumour Society score was 24 out of 30 (range 21-29). Resection of grade 3 proximal humerus giant cell tumour and reconstruction with prosthesis results in low recurrence rate and good functional outcome and is a valuable treatment option for such tumours.

Pseudoparalysis Secondary to Vitamin C Deficiency: A Rare Presentation in a Toddler.

CASE: We present a 17-month-old girl with postencephalitic sequelae only on high-calorie cereal milk through a nasogastric tube. She presented with a 3-week history of swelling and decreased lower limb movements. Synovial fluid analysis ruled out septic arthritis. Plain radiograph and magnetic resonance imaging (MRI) were suggestive of scurvy. She was diagnosed to have pseudoparalysis secondary to scurvy. She was started on vitamin C supplements, after which she showed good clinical improvement. CONCLUSION: This case report is to re-emphasize the need for awareness of the possibility of scurvy in children with poor nutritional status due to feeding difficulties.

Kaposi's sarcoma associated herpes virus (KSHV) induced COX-2: a key factor in latency, inflammation, angiogenesis, cell survival and invasion.

Kaposi's sarcoma (KS), an enigmatic endothelial cell vascular neoplasm, is characterized by the proliferation of spindle shaped endothelial cells, inflammatory cytokines (ICs), growth factors (GFs) and angiogenic factors. KSHV is etiologically linked to KS and expresses its latent genes in KS lesion endothelial cells. Primary infection of human micro vascular endothelial cells (HMVEC-d) results in the establishment of latent infection and reprogramming of host genes, and cyclooxygenase-2 (COX-2) is one of the highly up-regulated genes. Our previous study suggested a role for COX-2 in the establishment and maintenance of KSHV latency. Here, we examined the role of COX-2 in the induction of ICs, GFs, angiogenesis and invasive events occurring during KSHV de novo infection of endothelial cells. A significant amount of COX-2 was detected in KS tissue sections. Telomerase-immortalized human umbilical vein endothelial cells supporting KSHV stable latency (TIVE-LTC) expressed elevated levels of functional COX-2 and microsomal PGE2 synthase (m-PGES), and secreted the predominant eicosanoid inflammatory metabolite PGE2. Infected HMVEC-d and TIVE-LTC cells secreted a variety of ICs, GFs, angiogenic factors and matrix metalloproteinases (MMPs), which were significantly abrogated by COX-2 inhibition either by chemical inhibitors or by siRNA. The ability of these factors to induce tube formation of uninfected endothelial cells was also inhibited. PGE2, secreted early during KSHV infection, profoundly increased the adhesion of uninfected endothelial cells to fibronectin by activating the small G protein Rac1. COX-2 inhibition considerably reduced KSHV latent ORF73 gene expression and survival of TIVE-LTC cells. Collectively, these studies underscore the pivotal role of KSHV induced COX-2/PGE2 in creating KS lesion like microenvironment during de novo infection. Since COX-2 plays multiple roles in KSHV latent gene expression, which themselves are powerful mediators of cytokine induction, anti-apoptosis, cell survival and viral genome maintainence, effective inhibition of COX-2 via well-characterized clinically approved COX-2 inhibitors could potentially be used in treatment to control latent KSHV infection and ameliorate KS.

An alternative method for reconstructing anterior segmental mandibulectomy defects with a plate and pectoral major muscle flap.

Background: Reconstruction of anterior segmental mandibulectomy still remains a challenge. Osteocutaneous free flap remains the ideal choice of reconstruction because it restores cosmesis and function. The use of other locoregional flaps compromises cosmesis and function. Here, we have introduced a unique technique of reconstruction with lingual cortex mandibular plate as an alternate choice for free flap. Method: Six patients aged 12-62 years underwent oncological resection for oral cancer which involved the anterior segment of the mandible. Following resection, they underwent lingual cortex mandibular plating with pectoralis major myocutaneous flap reconstruction. Adjuvant radiotherapy was delivered to all patients. Results: The mean bony defect was 9.2 cm. There were no significant perioperative events related to the surgery. None required tracheostomy and all were safely extubated with no post-surgical complications. The cosmetic and functional outcomes were acceptable. Following the completion of radiotherapy with a median follow-up of 11 months, Plate exposure occurred in one patient. Conclusion: The technique is cheap, quick and simple, and can be effectively applied in resource-constrained and demanding situations. It is possible to consider this as an alternative treatment strategy for osteocutaneous free flap in anterior segmental defects.

MRI- and PET-Based Assessment of Radiological and Clinical Factors Associated With Cervical Cancer Response to External Beam Radiation Therapy.

Introduction In the era of MRI-guided external beam radiation therapy (EBRT), complete radiological response (CR) is often seen in cervical cancer (CC) with 4-6 weeks of chemotherapy and EBRT. The clinical and radiological factors associated with this observation were investigated in this study. Materials and methods One hundred and twenty-four CC patients treated with concurrent chemotherapy, EBRT, and brachytherapy (BT) from January 2008 to July 2015 were retrospectively screened. Initial primary gross tumor volume (GTVINITIAL) was estimated after contouring on a planning CT scan registered with pre-EBRT PET and MRI. The maximum standardized uptake value (SUV) of GTVINITIAL from each PET scan report was collected. Spearman's rank correlation coefficient (rho) values were calculated to assess the relationships among age, tumor size, and SUV. Tumor radiological response during EBRT prior to BT was calculated by contouring the final primary gross tumor volume (GTVFINAL) using MRI obtained prior to BT. CR rates during EBRT were estimated from GTVINITIAL and GTVFINAL and compared by the level of various factors using Fisher's exact test (two-sided).  Results Forty-eight patients met the inclusion criteria of the study with a median age of 50 years. The median GTVINITIAL was 82 cc. The median SUV was 14.9. A significant correlation was seen between SUV and GTVINITIAL with a larger tumor size associated with a higher SUV. CR rates were numerically higher for patients who were aged <50 years, or with >37.5 Gy radiation dose at or before the second MRI, or with GTVINITIAL <100 cc, or with no nodes involved or with stages IB or IIA. Conclusions Our study identified higher CC primary tumor CR rates during EBRT in younger patients (<50) with smaller tumors (100 cc) without nodal involvements as well as a positive correlation between PET FDG (18F-fluorodeoxyglucose)-SUV and CC primary tumor size.

Profile and outcome of COVID-19 patients treated at a secondary hospital in Central India during the second wave of the pandemic.

Background: The second wave of the coronavirus disease 2019 (COVID-19) pandemic resulted in a significant rise in the number of infections and deaths as compared to the first wave. The published literature till now is limited to tertiary hospitals. We did this study to describe the demographic characteristics and outcomes of patients admitted to a secondary care hospital in central India during the second wave of the pandemic. Methods: This was a single-center, retrospective observational study conducted in a secondary hospital in central India. The data of patients with COVID-19 infection admitted between March 25 to May 25, 2021, were retrieved and analyzed. Results: A total of 184 patients were included in the study. The mean age was 54.8 ± 14.5 years. Comorbidities included hypertension (40.2%), diabetes mellitus (29.9%), hypothyroidism (4.3%), and asthma (2.7%). The most common presenting complaints were cough (78.8%), breathlessness (61.4%), and fever (60.9%). The mean duration of symptoms was 5.4 ± 2.6 days. According to High-Resolution Computerised Tomography (HRCT) chest severity score, 29/181 (16%) patients had mild disease, 135/181 (74.5%) patients had moderate disease, and 17/181 (9.5%) patients had severe disease. The majority of the patients received remdesivir (90.2%) and 123 patients (66.8%) received corticosteroids. Half the patients (52.2%; n = 96) required intensive care unit admission, 79.3% (145 patients) required oxygen support, and 8.1% (15 patients) required non-invasive ventilator support. Conclusion: Our study from a secondary hospital setup showed that the second wave was very severe with a high requirement of oxygen support and intensive care monitoring.

NFAT and CREB regulate Kaposi's sarcoma-associated herpesvirus-induced cyclooxygenase 2 (COX-2).

COX-2 has been implicated in Kaposi's sarcoma-associated herpesvirus (KSHV) latency and pathogenesis (A. George Paul, N. Sharma-Walia, N. Kerur, C. White, and B. Chandran, Cancer Res. 70:3697-3708, 2010; P. P. Naranatt, H. H. Krishnan, S. R. Svojanovsky, C. Bloomer, S. Mathur, and B. Chandran, Cancer Res. 64:72-84, 2004; N. Sharma-Walia, A. G. Paul, V. Bottero, S. Sadagopan, M. V. Veettil, N. Kerur, and B. Chandran, PLoS Pathog. 6:e1000777, 2010; N. Sharma-Walia, H. Raghu, S. Sadagopan, R. Sivakumar, M. V. Veettil, P. P. Naranatt, M. M. Smith, and B. Chandran, J. Virol. 80:6534-6552, 2006). However, the precise regulatory mechanisms involved in COX-2 induction during KSHV infection have never been explored. Here, we identified cis-acting elements involved in the transcriptional regulation of COX-2 upon KSHV de novo infection. Promoter analysis using human COX-2 promoter deletion and mutation reporter constructs revealed that nuclear factor of activated T cells (NFAT) and the cyclic AMP (cAMP) response element (CRE) modulate KSHV-mediated transcriptional regulation of COX-2. Along with multiple KSHV-induced signaling pathways, infection-induced prostaglandin E(2) (PGE(2)) also augmented COX-2 transcription. Infection of endothelial cells markedly induced COX-2 expression via a cyclosporine A-sensitive, calcineurin/NFAT-dependent pathway. KSHV infection increased intracellular cAMP levels and activated protein kinase A (PKA), which phosphorylated the CRE-binding protein (CREB) at serine 133, which probably led to interaction with CRE in the COX-2 promoter, thereby enhancing COX-2 transcription. PKA selective inhibitor H-89 pretreatment strongly inhibited CREB serine 133, indicating the involvement of a cAMP-PKA-CREB-CRE loop in COX-2 transcriptional regulation. In contrast to phosphatidylinositol 3-kinase and protein kinase C, inhibition of FAK and Src effectively reduced KSHV infection-induced COX-2 transcription and protein levels. Collectively, our study indicates that mediation of COX-2 transcription upon KSHV infection is a paradigm of a complex regulatory milieu involving the interplay of multiple signal cascades and transcription factors. Intervention at each step of COX-2/PGE(2) induction can be used as a potential therapeutic target to treat KSHV-associated neoplasm and control inflammatory sequels of KSHV infection.

Effectiveness of health education on awareness of child sex abuse among school children.

Introduction: Child sexual abuse (CSA) is a serious and hidden problem in India. Despite being such a huge problem a culture of silence surrounds the subject of CSA. Empowering children to protect themselves and disclose the abuse is the only way to overcome the hidden problem of CSA. Hence the present study was designed to evaluate the effectiveness of health education. Methodology: Health education through interactive power point discussion and video was imparted to 200 girls of class 6th to 12th in Government higher secondary school, Coimbatore. Baseline data was collected using self-administered questionnaire. A week after the base line assessment, health education was delivered in five sessions with forty students per session. Interactive session lasting for 60 minutes using power point and videos were used to educate children. Follow-up data was collected after two months using the same questionnaire. Results: Initially only 23% of girls were aware about child sex abuse, and then, after intervention witnessed significant improvement to 71.5%. Similarly only 19% of girls were aware of various types of child sex abuse prior to intervention, however significant number of girls became aware post intervention. There was significant improvement in proportion of children (94.5%) who agreed that they will report bad touch to someone they trust until that person believes them. Pre-intervention only 31% of children knew as to what to do if sexually abused, this percentage rose significantly after the intervention. There was a significant improvement in knowledge from 49% to 78% post intervention regarding laws to protect children from sexual offences. Almost 90% of children reported that they knew about the child help line number. Conclusion: In this study has proven that health education imparted to girls has improved their knowledge and empowered them to report the events and protect themselves from such incidents.

Composite Grip Strength as a Marker of Outcome in Patients Surgically Treated for Degenerative Cervical Myelopathy.

STUDY DESIGN: Retrospective case series. PURPOSE: This study aimed to examine the efficacy of composite grip strength as a marker of surgical outcome in patients with moderate to severe degenerative cervical myelopathy. OVERVIEW OF LITERATURE: Degenerative cervical myelopathy causes loss of dexterity, muscle strength, and sensations in the hand. The impact of surgical management on improvement in composite grip strength has received scant attention. METHODS: This retrospective study was performed on degenerative cervical myelopathy patients with a complete composite grip strength assessment between January 2013 to January 2019. The Biometrics E-link hand kit was used for the assessment. The following parameters were measured: maximum grip strength, sustained grip strength, three-jaw pinch, maximum key pinch, and sustained key pinch. The pre- and postoperative functional status was assessed using the Nurick grade and the modified Japanese Orthopaedic Association (mJOA) score. RESULTS: A total of 40 patients were included in the study. The mean patient age was 51.9 years. The mean preoperative Nurick grade was 3.5 and the mJOA score was 10.9. The anterior approach was used in 25 patients, and the posterior approach was used in 15 patients. Four patients developed complications. Degenerative cervical myelopathy resulted in decreased handgrip and pinch strength as compared to normative Indian data. There was a significant improvement in the postoperative composite grip strength for all five parameters. There was no differential improvement between the anterior and posterior surgical groups. The improvement in the composite grip strength correlated with the improvement in functional scores. CONCLUSIONS: Composite grip strength analysis is an objective method for assessing the impact of degenerative cervical myelopathy on grip strength and monitoring the postoperative improvement. Decompressive surgery resulted in global improvement in all the parameters of composite grip strength.

Abnormal micronuclear telomeres lead to an unusual cell cycle checkpoint and defects in Tetrahymena oral morphogenesis.

Telomere mutants have been well studied with respect to telomerase and the role of telomere binding proteins, but they have not been used to explore how a downstream morphogenic event is related to the mutated telomeric DNA. We report that alterations at the telomeres can have profound consequences on organellar morphogenesis. Specifically, a telomerase RNA mutation termed ter1-43AA results in the loss of germ line micronuclear telomeres in the binucleate protozoan Tetrahymena thermophila. These cells also display a micronuclear mitotic arrest, characterized by an extreme delay in anaphase with an elongated, condensed chromatin and a mitotic spindle apparatus. This anaphase defect suggests telomere fusions and consequently a spindle rather than a DNA damage checkpoint. Most surprisingly, these mutants exhibit unique, dramatic defects in the formation of the cell's oral apparatus. We suggest that micronuclear telomere loss leads to a "dynamic pause" in the program of cortical development, which may reveal an unusual cell cycle checkpoint.

Time required for haemostasis under pressure from dental extraction socket.

INTRODUCTION: It is generally expected that the time required for a clot to form in an extraction socket must be similar to that of the average physiological bleeding time (2-9 minutes). However, in dental practice does hemostasis require the full clot to form or does it occur earlier? Conventionally there is no accepted average time range for socket hemostasis with estimates ranging from 20 minutes to 40 minutes. This study is an attempt to quantify the average time period required for hemostasis to occur in an extraction socket. METHODOLOGY: 1205 consecutive patients attending the dental clinic and requiring dental extractions were evaluated for the average duration of hemostasis after extraction. Exclusion criteria were children (<15 years), pregnant mothers and patients who had a systemic bleeding disorder or were on anticoagulants. The socket was inspected first after five minutes after an extraction and later at 10 minutes and 15 minutes if bleeding continued. RESULTS: Bleeding from an extraction socket settled in less than five minutes in about 83% of individuals and in 10 minutes in 96.5% of cases. Hence it is expected that in an otherwise normal healthy individual socket compression by biting over gauze for around 10 minutes will produce adequate haemostasis. Prolonged bleeding beyond 10 minutes was rare and was controlled with suturing and pressure applied with a gauze pack in healthy individuals. CONCLUSION: Checking for hemostasis after placing a pressure pack for 5-10 minutes over an extraction socket is a useful act of risk management before discharge of the patient from the clinic to rule out any hemorrhagic tendency.

Affibody-Mediated Sequestration of Amyloid ß Demonstrates Preventive Efficacy in a Transgenic Alzheimer's Disease Mouse Model.

Different strategies for treatment and prevention of Alzheimer's disease (AD) are currently under investigation, including passive immunization with anti-amyloid ß (anti-Aß) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential of a novel type of Aß-targeting agent based on an affibody molecule with fundamentally different properties to mAbs. We generated a therapeutic candidate, denoted ZSYM73-albumin-binding domain (ABD; 16.8 kDa), by genetic linkage of the dimeric ZSYM73 affibody for sequestering of monomeric Aß-peptides and an ABD for extension of its in vivo half-life. Amyloid precursor protein (APP)/PS1 transgenic AD mice were administered with ZSYM73-ABD, followed by behavioral examination and immunohistochemistry. Results demonstrated rescued cognitive functions and significantly lower amyloid burden in the treated animals compared to controls. No toxicological symptoms or immunology-related side-effects were observed. To our knowledge, this is the first reported in vivo investigation of a systemically delivered scaffold protein against monomeric Aß, demonstrating a therapeutic potential for prevention of AD.

Osteoradionecrosis of Jaw: An Institutional Experience.

AIMS AND OBJECTIVES: Osteoradionecrosis (ORN) of the jaw is a significant yet rare complication of radiotherapy (RT) associated with the management of head-and-neck malignancies. Recent decrease in the incidence of ORN following RT to the head and neck is being mainly attributed to refinement in RT techniques and improvement in our understanding of this morbid disease. The aim of this study is to assess the patients with ORN following head-and-neck RT to determine the various contributing risk factors involved in the development of ORN. SUBJECTS AND METHODS: A retrospective data review from 2003 onward was conducted on the cases of ORN which presented to the Department of Dental and Oral Surgery, Christian Medical College, Vellore. Details of the patients with regard to the site of primary malignancy, type of treatment provided - RT alone or in combination of surgery and chemotherapy, dose of RT, presenting complaint, duration between the RT and presentation of ORN, and method of management considered were evaluated. RESULTS: A total of 25 patients were evaluated. The average age of the 25 patients in our study was 58 years. Oropharynx (about 50%) was the leading site of primary malignancy. More than half of the patients in the study (52%) had undergone radical RT for the primary malignancy and all the patients were given >60 Gy dose of RT. About 48% of the patients in the study reported with pus discharge as their chief complaint. The average intervening time period from completion of RT to the presentation of ORN was 48 months. The mandibular alveolus was the most common site for ORN. Twelve of the 25 cases in the study were managed conservatively with only 3 patients requiring major resection. CONCLUSION: Due to its rare presentation, ORN still remains a challenge for the clinician in its management. Our study revealed that radical RT and concurrent chemo-RT for the oropharyngeal and base of the tongue malignancies have a higher risk of developing ORN. Patients subjected to the dose of RT above 60 Gy for head-and-neck malignancies have an increased risk of future ORN; henceforth, newer modality treatment like intensity-modulated RT regimen is recommended for such sites. Most of the patients in the study were satisfactorily managed of the symptoms with conservative modality treatment; hence, it is recommended to consider for surgical methods only in severe end-stage form of ORN.