Primary central nervous system angiitis: a case report.

Introduction: Primary central nervous system angiitis is a rare idiopathic vasculitis that is limited to the central nervous system. It has a wide range of clinical presentations that can mimic other vasculopathies. Case presentation: A 24-year-old female patient presents with various non-specific neurological complaints in a progressive course. After a challenging diagnostic work-up, she was diagnosed by tissue biopsy to have primary central nervous system angiitis. Discussion: Although primary central nervous system angiitis has been reported increasingly recently, its pathogenesis is still unknown, and its diagnosis is still very challenging. No universal criteria have been adopted, and there is no laboratory test or imaging modality with sufficient sensitivity and specificity to confirm the diagnosis and exclude other mimickers. Conclusion: To prevent misdiagnosis, clinicians treating patients with suspected primary central nervous system angiitis should be aware of its differentials.

From Trauma to Triumph: Navigating the Complexities of a Central Hip and Ipsilateral Knee Dislocation with Associated Fractures.

Introduction: Central hip dislocations are rare orthopedic injuries, and their concomitant occurrence with ipsilateral knee dislocations is an even rarer phenomenon. We present a unique case of central hip dislocation along with ipsilateral knee dislocation and additional fractures involving the lateral condyle of the left tibia and patella. This complex injury pattern resulted from a severe road traffic accident, necessitating operative management to address the multiple musculoskeletal injuries. Ultimately, femoral head avascular necrosis (AVN) developed, leading to the need for total hip replacement (THR). Case Report: A 28-year-old male was involved in a high-impact road traffic accident, leading to central hip dislocation, ipsilateral knee dislocation, and fractures of the lateral condyle of the left tibia and patella. The patient was promptly assessed, and operative intervention was initiated. Closed reduction and internal fixation with K-wires were performed for the fractures of the lateral condyle of the left tibia and patella. For the central hip dislocation, open reduction was achieved using a 9-hole RECON plate. Following the procedures, a long leg slab was applied for 6 weeks to facilitate optimal healing.Postoperatively, at the 6-week mark, K-wires were removed, and the patient commenced physiotherapy with partial weight-bearing permitted. However, during the rehabilitation phase, the patient reported instability in his left knee. Magnetic resonance imaging revealed an avulsion fracture of the posterior cruciate ligament (PCL) from its tibial attachment site and a complete anterior cruciate ligament (ACL) tear. It was observed that the femoral head had developed AVN. This complication necessitated further intervention, leading to the performance of a THR. Discussion: This case underscores the challenges and complexities associated with managing central hip dislocation and ipsilateral knee dislocation with multiple fractures. The post-operative instability of the knee, diagnosed as an avulsion fracture of the PCL and complete ACL tear, necessitated additional intervention. The patient subsequently underwent PCL reconstruction using a semitendinosus graft, highlighting the importance of a comprehensive approach to address the diverse musculoskeletal injuries resulting from high-impact trauma. Conclusion: The successful management of central hip dislocation and ipsilateral knee dislocation with associated fractures requires a multidisciplinary approach, incorporating timely surgical intervention, rigorous rehabilitation, and vigilant post-operative monitoring to address potential complications. This case emphasizes the need for ongoing clinical assessment and imaging studies to identify and manage secondary injuries that may manifest during the recovery phase. In addition, it highlights the development of femoral head AVN, ultimately leading to the necessity for THR.

A Laboratory-Scale Evaluation of Smart Pebble Sensors Embedded in Geomaterials.

This paper introduces a novel approach to measure deformations in geomaterials using the recently developed 'Smart Pebble' sensors. Smart Pebbles were included in triaxial test specimens of unbound aggregates stabilized with geogrids. The sensors are equipped with an aggregate particle/position tracking algorithm that can manage uncertainty arising due to signal noise and random walk effects. Two Smart Pebbles were placed in each test specimen, one at specimen's mid-height, where a geogrid was installed in the mechanically stabilized specimen, and one towards the top of the specimen. Even with simple raw data processing, the trends on linear vertical acceleration indicated the ability of Smart Pebbles to assess the geomaterial configuration and applied stress states. Employing a Kalman filter-based algorithm, the Smart Pebble position coordinates were tracked during testing. The specimen's resilient deformations were simultaneously recorded. bender element shear wave transducer pairs were also installed on the specimens to further validate the Smart Pebble small-strain responses. The results indicate a close agreement between the BE sensors and Smart Pebbles estimates towards local stiffness enhancement quantification in the geogrid specimen. The study findings confirm the viability of using the Smart Pebbles in describing the resilient behavior of an aggregate material under repeated loading.

Functional Outcomes and Gait Analysis of Total Hip Arthroplasty Through Lateral Hardinge Approach and Gluteus Medius-Sparing Approach: A Prospective Study.

Background and objective Hip degenerative joint disease is a common and debilitating musculoskeletal disorder. Total hip arthroplasty (THA) is a reconstructive hip procedure to relieve this condition through various surgical approaches. This study aimed to compare the functional outcomes between patients undergoing THA using the lateral Hardinge approach and the lateral gluteus medius-sparing approach. Material and methods This prospective study was carried out at a tertiary care institution. Thirty patients with arthritic hip joints were managed with total hip replacement (THR). The patients were allocated into two treatment groups; in group A, 14 patients received a THR by the lateral Hardinge approach, whereas in group B, 16 patients were managed by the lateral gluteus medius-sparing approach. Functional outcomes were assessed by the Harris Hip Score (HHS), and gait analysis was performed. Results The mean age of group A was 39.79 ±14.01 years and that of group B was 37.00 ±14.81 years. The mean length of incision was significantly lower in group B (p=0.001), whereas the mean duration of surgery (p=0.018) and mean contralateral pelvic tilt were found to be significantly lower in group A (p=0.009). No significant difference was found in abductor muscle strength, limb length discrepancy, HHS, pelvic obliquity, and pelvic rotation. Conclusion While functional outcomes were similar in both groups, the group that underwent THA with the gluteus medius-sparing approach had better gait based on lower pelvic tilt.

Tibial Tuberosity Avulsion Fracture with Epiphyseal Injury in a Soccer Player: Treatment Options and Challenges.

Introduction: Acute avulsion of the tibial tubercle is an uncommon fracture, with reported incidence rates of 0.4-2.7% of all epiphyseal injuries and <1% of all physeal injuries. Typically, these fractures present with marked displacement of the entire proximal apophysis, with or without intra-articular extension, and variable associated soft-tissue injury. The Ogden classification has historically directed both non-operative and operative treatment of this injury. The overarching objective of several fracture fixation techniques has been outlined as being to restore the joint surface and the extensor mechanism. Case Report: This case report describes the management of a 14-year-old male who sustained a rare avulsion fracture of the left tibial tuberosity with epiphyseal injury during a soccer game. The fracture was classified as Ogden Type III-B, indicating an intra-articular extension. The patient underwent open reduction and internal fixation with three cannulated screws and tension band wiring. Conclusion: The fracture united with no residual deformity and return of full range of motion. Tension band wiring provides stable reduction; hence, prompt diagnosis and appropriate surgical intervention in similar cases is important to optimize outcomes.

Polidocanol sclerotherapy for the treatment of aneurysmal bone cyst, with or without pathological fractures: A prospective, comparative study.

Introduction: Polidocanol sclerotherapy in the treatment of aneurysmal bone cysts (ABCs) with or without pathological fractures has been a topic of debate. While some studies recommend intralesional curettage as the preferred treatment, others suggest intralesional sclerosants as an effective alternative. Material and methods: This study evaluates the use of polidocanol-based percutaneous sclerosant therapy in 28 patients with ABCs, of which 8 patients had pathological fracture. The patients received injections every four weeks based on clinical and radiological evaluation of the cyst, and the study assessed the results and complications of the treatment. Results: In group A (without pathological fractures), 14 out of 17 (82.4 %) lesions healed without any significant residual lesion. Three out of 17 (17.6 %) patients required further surgical intervention and were treated by curettage and bone grafting, definitively. Minor local inflammatory reaction was observed in 3 patients, which resolved without intervention within 3-4 days. In group B, all the 8 patients (100 %) with pathological fracture in their lesions healed as Grade 1 healing, without any significant residual lesion. One patient developed an episode of anesthesia related complication (delayed recovery) which resolved within an hour, without any residual effect. At final follow up, no recurrence was seen in any patient. Conclusion: The study concludes that polidocanol sclerotherapy is an effective treatment option for patients with ABCs, with or without pathological fractures, and has the potential to become the new treatment of choice for pathological fractures due to its low invasiveness, low morbidity, and affordability. However, further research is needed to confirm the efficacy of polidocanol sclerotherapy in larger patient populations and to compare its effectiveness with other treatment options.

Orthopaedic problems in the blind.

Background: Blindness is a common problem in every society and country. The problem ranges from complete blindness to partially sighted in the affected population. India has close to 12 million visually impaired people. Orthopaedic problems are not uncommon in blind. Orthopaedic Surgeons though had been aware of the postural and gait abnormalities in blind but very few published studies have systematically focused on the effect of blindness on the development of posture and gait. Methods: Case Control study done for the orthopaedic evaluation of the blind and partially sighted individuals. The study population included 242 students of Ahmadi School for the Blind, Aligarh Muslim University, Aligarh (India), as the cases and another matched set of 250 non-blind children. All the children were assessed for the orthopaedic problems like degree of ligamentous laxity, spinal alignment, foot morphology and alignment of hips, knees and ankles. Standing posture and gait were also examined and recorded. Ligamentous laxity was assessed according to the method adopted by Beighton et al.10 Chi-square test was applied using IBM SPSS 23.0. Results: 139 children (57.4 %) were found to have laxity of the ligaments. 72 children (29.7 %) had spine deformities, out of which kyphosis was present in 34 (47.2 %), scoliosis in 23 (31.9 %), lordosis in 13 (18.0 %), and meningomyelocele in 2 (2.9 %) children. 119 children (49.1 %) had foot deformities. 37 children (15.2 %) had knee deformity. 22 children (9.0 %) showed evidence of cerebral palsy. 216 children (89.2 %) had varying degrees of postural abnormalities. The data was statistically significant when compared with the control group (P < 0.05). Conclusion: Blindness causes a wide range of complicated sensory and motor problems that frequently forces people into isolation. Blind rehabilitation requires an interdisciplinary approach. Orthopaedic problems are quite common in blind individuals and should be dealt separately.

Nonunion of an Isolated Medial Condyle of a Femur Hoffa Fracture in a 21-Year-Old Male: A Case Report.

Isolated Hoffa fractures of the femur are often missed on initial radiographic evaluations. Routine CT scans for intraarticular fractures in suburban populations are not routinely done. Nonunion of medial condyle Hoffa fracture of the distal femur is a rare finding and presents late with pain in weight-bearing and painful flexion. This is a case report of a 21-year-old male who sustained trauma as a result of a motorcycle-car collision and was managed elsewhere conservatively on an above-knee slab. He presented after five months to our side with a limited range of movement at the knee and pain during ambulation. After radiological work diagnosis of isolated non-union of medal condyle Hoffa fracture of the distal femur was made, the patient was managed by freshening of fracture followed by rigid fixation with cancellous screws and reconstruction plate. At postoperative six weeks, the patient had a painless full range of motion at the knee joint.

Bilateral Distal Humeral Physeal Separation-From Birth Trauma to Family Trauma.

Introduction: Chondro-epiphyseal separation of the distal humerus is a rare injury, which can occur as a consequence of excessive traction on the upper extremity accompanying a dystocic birth or one complicated by cephalopelvic disproportion. Such fracture patterns can also result from a combination of rotatory and shear forces, also typically seen following child abuse. It can be easily mistaken for a posterior elbow dislocation, creating a delay in diagnosis. Since unossified cartilage cannot be seen radiographically, these injuries are better appreciated by ultrasound or magnetic resonance imaging. Case Report: We present a case of an 8-day-old neonate who presented with pseudoparesis of the left arm following birth. Posterior displacement of the elbow joint was identified on the radiograph. On ultrasound, a trans-physical supracondylar distal humerus fracture was identified. This was presumed as trauma secondary to a difficult delivery. At the 11th week of follow-up, the patient presented with a fracture of the right proximal tibia, followed by a fracture shaft left femur at 5 months of follow-up. Chest X-ray at this time revealed uniting rib fractures with callus formation. After ruling out any congenital collagen disorder (osteogenesis imperfecta), the patient was diagnosed with a case of battered baby syndrome. The case was reported to child protection services and parents were questioned and counseled for the same. Conclusion: This case report highlights the importance of a high degree of suspicion of child abuse in any child with a rare fracture pattern, uncommon serial fracture occurrence, and unconventional clinic-radiological presentation.

Outcomes of BDSF technique for osteosynthesis of femoral neck fractures.

INTRODUCTION: Femoral neck fractures present a significant challenge for orthopedic surgeons, especially in young patients who want to preserve their natural femoral head. Conventional methods for fixing these fractures often lead to poor outcomes and high complication rates. The Biplane Double-supported Screw Fixation (BDSF) technique is a novel approach that involves placing screws in two planes simultaneously, creating a two-point support for the screws in the neck and head of the femur. METHODS: This study aimed to evaluate the effectiveness of the BDSF technique in treating femoral neck fractures in patients aged 20-60 years. A total of 28 patients with fresh femoral neck fractures (less than three weeks old) were treated with closed reduction and internal fixation using the BDSF method. The patients' functional outcomes were evaluated using the Harris hip score, and the radiographic outcomes of union, femoral neck shortening, screw back-out, and femoral head avascular necrosis (AVN) were also evaluated. RESULTS: The results showed that the BDSF technique is a safe and effective method for treating femoral neck fractures in young adults. Out of the 25 patients who were followed up for a mean time of 18 months (range 6-24 months), 20 (80%) achieved fracture union in a mean time of 5.2 months. Non-union occurred in five patients (20%), and AVN of the femoral head was observed in three patients (12%). Two patients experienced varus collapse, but their fractures united successfully. CONCLUSION: The BDSF technique offers several advantages over conventional methods, including increased stability and improved fixation strength. It can be considered as an alternative to conventional methods for managing femoral neck fractures in young adults, with a low incidence of non-union and avascular necrosis and no cases of fixation failure or varus collapse.

First Report on Microplastics Quantification in Poultry Chicken and Potential Human Health Risks in Pakistan.

Microplastics (MPs) are an emerging environmental health concern due to their widespread occurrence in food sources such as fish, meat, chicken, honey, sugar, salt, tea and drinking water, thereby posing possible risks to human health. This study aimed to observe the existence of MPs in the crop and gizzard of the farm chicken, a significant food source in Pakistan. Twenty-four chicken samples were taken from eight poultry farms across Punjab, Pakistan. A total of 1227 MP particles were found from 24 samples (crop and gizzards) originating from the 8 poultry farms. In all, 429 MP particles were found in 24 chicken crops, with a mean of 17.8 ± 12.1 MPs/crop. In contrast, 798 MP particles were found in 24 chicken gizzards, with a mean of 33.25 ± 17.8 MPs/gizzard. Comparatively larger particles, ranging between 300-500 µm, were more abundant (63%) than other considered sizes (300-150 µm [21%] and 150-50 µm [16%]). Additionally, fragments were the dominant type of shape in both sample types (crop [64%] and gizzard [53%]). The predominant colours of particles extracted from gizzards and crops were yellow (32%) and red (32%), respectively. Chemical characterisation of these particles detected four types of polymers: polyvinyl chloride (PVC) at 51.2%, followed by low-density polyethylene (LDPE) at 30.7%, polystyrene (PS) at 13.6% and polypropylene homopolymer (PPH) at 4.5%. In conclusion, we provide evidence for MPs in the gizzards and crops of farmed chickens which may originate from contaminated poultry feed. Only a few studies have been reported globally to assess MPs ingestion in chickens. The current study is the first report from Pakistan. It could be a valuable addition to support MPs literature to establish a relationship between MPs contamination and intake through the food chain.

Interactions between diabetic and hypertensive drugs: a pharmacogenetics approach.

Diabetes is known to increase susceptibility to hypertension due to increase in inflammation, oxidative stress, and endothelial dysfunction, leading to vascular stiffness. The polytherapy might lead to several drug-drug interactions (DDIs), which cause certain life-threatening complications such as diabetic nephropathy and hypoglycaemia. So, in this review we focused on drug-drug interactions and impact of genetic factors on drug responses for better disease management. Drug-drug interactions (DDIs) may act either synergistically or antagonistically. For instance, a combination of metformin with angiotensin II receptor antagonist or angiotensin-converting enzyme inhibitors (ACEIs) synergistically improves glucose absorption, whereas the same hypertensive drug combination with sulphonylurea might cause severe hypoglycaemia sometimes. Thiazolidinediones (TDZs) can cause fluid retention and heart failure when taken alone, but a combination of angiotensin II receptor antagonist with TZDs prevents these side effects. Interindividual genetic variation affects the DDI response. We found two prominent genes, GLUT4 and PPAR-γ, which are common targets for most of the drug. So, all of these findings established a connection between drug-drug interaction and genetics, which might be used for effective disease management.

Local Versus Systemic Tranexamic Acid in Total Hip Arthroplasty in Young Adults.

Background Total hip arthroplasty (THA) is the most successful orthopedic elective surgical procedure for end-stage hip arthritis. THA is linked with significant blood loss, ranging from 1,188 to 1,651 mL, and a transfusion rate of 16-37%, which frequently results in postoperative blood transfusions. Postoperative blood transfusions can be avoided by using autologous blood transfusion, intraoperative blood saving, local anesthetic, hypotensive anesthesia, and antifibrinolytic medications such as tranexamic acid (TXA) administration. Methodology A double-blinded, placebo-controlled, randomized, controlled study was conducted with three prospective groups to investigate the efficacy of topical and systemic routes of a single intraoperative dose (1.5 g) of TXA. Patients were recruited from our center between October 2021 to March 2022 who were undergoing primary total hip replacement. Estimated blood loss was calculated and compared in groups, and a p-value of <0.05 was taken as significant. Results A total of 60 patients were recruited in our study. Estimated blood loss was similar in both treatment groups, 816.8 ± 219.9 mL in the systemic TXA group and 775.5 ± 107.2 mL in the topical TXA group. The placebo group had 1,066.3 ± 150.4 mL estimated blood loss, which was significantly higher compared to the treatment groups. Conclusions Administration of TXA (1.5 g) significantly lowers blood loss without increasing problems, which can eliminate concerns about intravenous TXA use. TXA reduces blood loss by 270 mL on average.

Taste Preference-Related Genetic Polymorphisms Modify Alcohol Consumption Behavior of the Hungarian General and Roma Populations.

Harmful alcohol consumption has been considered a major public health issue globally, with the amounts of alcohol drunk being highest in the WHO European Region including Hungary. Alcohol consumption behaviors are complex human traits influenced by environmental factors and numerous genes. Beyond alcohol metabolization and neurotransmitter gene polymorphisms, taste preference-related genetic variants may also mediate alcohol consumption behaviors. Applying the Alcohol Use Disorders Identification Test (AUDIT) we aimed to elucidate the underlying genetic determinants of alcohol consumption patterns considering taste preference gene polymorphisms (TAS1R3 rs307355, TAS2R38 rs713598, TAS2R19 rs10772420 and CA6 rs2274333) in the Hungarian general (HG) and Roma (HR) populations. Alcohol consumption assessment was available for 410 HG and 387 HR individuals with 405 HG and 364 HR DNA samples being obtained for genotyping. No significant associations were found between TAS1R3 rs307355, TAS2R19 rs10772420, and CA6 rs2274333 polymorphisms and alcohol consumption phenotypes. Significant associations were identified between TAS2R38 rs713598 and the number of standard drinks consumed in the HG sample (genotype GG negatively correlated with the number of standard drinks; coef: -0.136, p = 0.028) and the prevalence of having six or more drinks among Roma (a negative correlation was identified in the recessive model; genotype GG, coef: -0.170, p = 0.049), although, none of these findings passed the Bonferroni-corrected probability criterion (p > 0.05). Nevertheless, our findings may suggest that alcohol consumption is partially driven by genetically determined taste preferences in our study populations. Further studies are required to strengthen the findings and to understand the drivers of alcohol consumption behavior in more depth.

Genetic polymorphisms of IL6 gene -174G > C and -597G > A are associated with the risk of COVID-19 severity.

Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (-597G > A and -174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (-174G > C) and rs1800797 (-597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (-174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (-597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having 'C' allele of IL6 (-174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (-174G > C) and rs1800797 (-597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that 'C' allele of rs1800795 (-174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.

The Impact of Taste Preference-Related Gene Polymorphisms on Alcohol Consumption Behavior: A Systematic Review.

Unhealthy alcohol consumption is recognized as a leading contributory factor to mortality and disability. In addition to other factors, taste sensation also mediates alcohol intake. The orosensation provoked by alcoholic drinks may vary across individuals and may be responsible for differences in preference for alcoholic beverages. Thus, individual genetic variability of taste preference may have an impact on alcohol consumption practices. The present review aimed to explore the associations between different taste preference polymorphisms and alcohol consumption behavior. Based on the PRISMA statement, the three databases PubMed, Web of Science and ProQuest Central were searched to identify articles and the Q-Genie tool was used to assess the quality of the included studies. Among the 17 studies included in this review, 5 and 12 were of good and moderate quality, respectively. Most of the studies analyzed TAS2R38 (taste 2 receptor member 38) rs713598, rs1726866, rs10246939 polymorphisms. Due to the inconclusive findings on these variants and the very limited number of studies on other polymorphisms, additional extensive research is recommended to replicate the existing findings, to generate new knowledge to enhance our understanding of the complexity of alcohol consumption behavior and to aid the development of personalized recommendations on unhealthy alcohol use.

Maggot debridement therapy and complementary wound care: a case series from Nigeria.

OBJECTIVE: Maggot debridement therapy (MDT) is an emerging procedure involving the application of sterile maggots of the Dipteran species (commonly Lucilia sericata) to effect debridement, disinfection and promote healing in wounds not responding to antimicrobial therapy. Data on MDT in sub-Saharan Africa (including Nigeria) are scarce. This study aimed to use medicinal grade maggots as a complementary method to debride hard-to-heal necrotic ulcers and thereby promote wound healing. METHOD: In this descriptive study, we reported on the first group of patients who had MDT at Aminu Kano Teaching Hospital (AKTH), a tertiary hospital in northern Nigeria. The first instar larvae of Lucilia sericata were applied using the confinement (free-range) maggot therapy dressing method under aseptic conditions. RESULTS: Diabetic foot ulcer (DFU) grade III-IV constituted more than half of the wounds (53.3%), followed by necrotising fasciitis (30%), and post-traumatic wound infection (10%). Others (6.7%, included pyomyositis, surgical site infection and post traumatic wound infection). The median surface area of the wounds was 56cm2. Of the 30 patients, half (50%) had two MDT cycles with a median time of four days. Of the wounds, 22 (73%) were completely debrided using maggots alone while eight (27%) achieved complete debridement together with surgical debridement. Wound culture pre-MDT yielded bacterial growth for all the patients and Staphylococcus aureus was the predominant isolate in 17 wounds (56.7%) while Pseudomonas aeruginosa and Streptococcus pyogenes were predominant in five wounds (16.7%) each. Only four (13.3%) wound cultures yielded bacterial growth after MDT, all Staphylococcus aureus. CONCLUSION: A good prognosis was achieved post-MDT for various wounds. MDT effectively debrides and significantly disinfects wounds involving different anatomical sites, thus enhancing wound healing and recovery. MDT is recommended in such wounds.

Understanding Role of DNA Repair and Cytochrome p-450 Gene Polymorphisms in Cervical Cancer Patient Treated With Concomitant Chemoradiation.

Background: Evidences suggest that single nucleotide polymorphisms (SNPs) can be considered as potential biomarkers for disease progression and therapeutic response in cervical cancer. The present study investigated the association of CYP1A1 T>C (rs4646903), CYP1A1 A>G (rs1048943), CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), XRCC1 G>A (rs25487), XRCC2 G>A (rs3218536) and XRCC3 C>T (rs861539) polymorphisms with treatment outcome of cisplatin based chemoradiation (CRT). Methods: Total 227 cervical cancer cases, treated with the same chemoradiotherapy regimen were selected for the study. Genotyping analysis was performed by PCR-restriction fragment length polymorphisms (PCR-RFLP). Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Association of all clinical data (responses, recurrence and survival of patients) and single nucleotide polymorphisms (SNPs) was analysed by using SPSS (version 21.0). Results: Patients with TA/AA genotype of CYP2E1 T>A polymorphism showed significantly poor response while those with GC/CC genotype of RAD51 G>C showed better response (p = 0.008, p = 0.014 respectively). Death was significantly higher in patients with GG genotypes of RAD51 G>C and XRCC1 G>A (p = 0.006, p = 0.002 respectively). Women with GC+CC genotype of RAD51 G>C and AG+GG of XRCC1 showed better survival and also reduced risk of death (HR = 0.489, p = 0.008; HR = 0.484, p = 0.003 respectively). Conclusion: Results suggested that CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), and XRCC1 G>A (rs25487) polymorphisms may be used as predictive markers for clinical outcomes in cervical cancer patients undergoing cisplatin based concomitant chemoradiotherapy.

Genetic Variants and Drug Efficacy in Tuberculosis: A Step toward Personalized Therapy.

Tuberculosis (TB) continues to be a major infectious disease affecting individuals worldwide. Current TB treatment strategy recommends the standard short-course chemotherapy regimen containing first-line drug, i.e., isoniazid, rifampicin, pyrazinamide, and ethambutol to treat patients suffering from drug-susceptible TB. Although Mycobacterium tuberculosis , the causing agent, is susceptible to drugs, some patients do not respond to the treatment or treatment may result in serious adverse reactions. Many studies revealed that anti-TB drug-related toxicity is associated with genetic variations, and these variations may also influence attaining maximum drug concentration. Thus, inter-individual diversities play a characteristic role by influencing the genes involved in drug metabolism pathways. The development of pharmacogenomics could bring a revolution in the field of treatment, and the understanding of germline variants may give rise to optimized targeted treatments and refine the response to standard therapy. In this review, we briefly introduced the field of pharmacogenomics with the evolution in genetics and discussed the pharmacogenetic impact of genetic variations on genes involved in the activities, such as anti-TB drug transportation, metabolism, and gene regulation.