En bloc resection followed by gluteal advancement flap for sacral Ewing's sarcoma: A novel technique.

Ewing's sarcoma is a rare and highly aggressive bone tumor primarily affecting children and adolescents. It commonly presents in the pelvic and axial skeleton, with sacral involvement posing unique challenges due to its intricate anatomical location. This report details the case of an 18-year-old male with sacral Ewing's sarcoma, emphasizing the diagnostic, surgical, and reconstructive aspects of management. The patient presented with lower back pain, lower limb weakness, and urinary incontinence, which prompted an extensive diagnostic evaluation. Magnetic resonance imaging and computed tomography scans revealed a large lytic mass extending from the S2 vertebra to the coccyx invading the presacral space. Biopsy confirmed the diagnosis of Ewing's sarcoma, characterized by the EWS-FLI1 type 1 translocation. A multidisciplinary team comprising neurosurgeons, colorectal surgeons, and plastic surgeons was formulated. En bloc resection of the tumor, lumbopelvic fixation, and soft-tissue reconstruction using bilateral gluteus maximus advancement flaps were successfully performed. The procedure aimed to address both the oncological and functional aspects of the patient's condition. Chemotherapy and radiotherapy were administered as adjuvant therapies. At 2-year follow-up, the patient was ambulating independently with no residual tumor on imaging. This case highlights the complex nature of sacral Ewing's sarcoma and underscores the importance of a multidisciplinary approach. The described surgical technique, including the innovative use of gluteus maximus advancement flaps for soft-tissue reconstruction, contributes to reducing wound complications and promoting successful patient outcomes. The presented approach serves as a valuable addition to the armamentarium of treatment options for this challenging malignancy.

Neuroprotective potential of saroglitazar in 6-OHDA induced Parkinson's disease in rats.

Parkinson's disease (PD) is a neurodegenerative disorder that affects 2%-3% of the population worldwide. Clinical presentation of PD includes motor and non-motor symptoms. The interplay between pathogenic factors such as increased oxidative stress, neuroinflammation, mitochondrial dysfunction and apoptosis are responsible for neurodegeneration in PD. Intrastriatal administration of 6-hydroxy dopamine (6-OHDA) in rat brain provoked oxidative and nitrosative stress by decreasing endogenous antioxidants such as superoxide dismutase, catalase, glutathione, glutathione peroxidase and glutathione reductase. Consequently, interleukin-6, tumour necrosis-α, interferon-γ and cyclooxygenase-2 mediated neuroinflammation leads to mitochondrial dysfunction, involving inhibition of complex-II and IV activities, followed by apoptosis and degeneration of striatal dopaminergic neurons. Degeneration of dopaminergic neurons resulted in reduced dopamine turnover, consequently induced behavioural abnormalities in rats. Activation of peroxisome proliferator-activated receptors (PPARs) have protective role in PD by modulating response of antioxidant enzymes, neuroinflammation and apoptosis in various animal models of PD. Saroglitazar (SG) being dual PPAR-α/γ agonist activates both PPAR-α and PPAR-γ receptors and provide neuroprotection by reducing oxidative stress, neuroinflammation, mitochondrial dysfunction and apoptosis of dopaminergic cells in 6-OHDA induced PD in rats. Thereby, SG restored striatal histopathological damage and dopamine concentration in rat striatum, and behavioural alterations in rats. Thus, SG proved neuroprotective effects in rat model of PD. Potential benefits of SG in rat model of PD advocates to consider it for further preclinical and clinical evaluation.

Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities.

Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.

Geraniol protects hippocampal CA1 neurons and improves functional outcomes in global model of stroke in rats.

Geraniol (GE), an acyclic monoterpene, is a chief constituent of essential oils of herbs and fruits. It possesses diverse pharmacological actions like antioxidant, anti-inflammatory, anti-apoptotic, and anti-parkinson. However, its neuroprotective potential in stroke is yet to be explored at large. The present study evaluated the neuroprotective potential of GE against the global model of cerebral ischemia/reperfusion (I/R)-injury in rats. Bilateral common carotid artery (BCCA) occlusion for 30 min followed by 7 days of reperfusion caused varied biochemical/enzymatic alterations viz. increase in levels of lipid peroxidation (LPO), nitric oxide (NO), xanthine oxidase (XO), and decrease in the levels of cerebroprotectives like superoxide dismutase (SOD), catalase (CAT), total thiols, and glutathione (GSH). GE-pretreatment markedly reversed these changes and restored the levels of protective enzymatic and non-enzymatic antioxidants near to normal compared to I/R group. Besides, GE treatment showed marked improvement in anxiety-related behavior and neuronal deficits in animals subjected to I/R injury. Moreover, 2,3,5-triphenyl tetrazolium chloride (TTC)-stained rat brain coronal sections and histopathological studies revealed neuronal protection against I/R-injury, as evidenced by a reduction in infarct area (%) and an increase in hippocampal CA1 neuronal density in the GE-treated groups. The results of this study revealed that GE exhibited potential neuroprotective activity by reducing oxidative stress and infarction area, and protecting hippocampal CA1 neurons against I/R-injury in the global stroke model in rats.

Oral Squamous Cell Carcinoma Following Acute Methotrexate Toxicity in a Psoriasis Patient: A Causal Association or Mere Co-Incidence.

BACKGROUND: Methotrexate is an antimetabolite anticancer drug frequently used in the treatment of extensive chronic plaque psoriasis. Psoriasis patients on treatment with immunosuppressants have an increased risk of developing malignancies. OBJECTIVE: To present a rare case of Oral Squamous Cell Carcinoma (OSCC) in a psoriasis patient postacute methotrexate toxicity. CASE REPORT: A 47-year-old female, a known case of chronic plaque psoriasis for which she was on 15 mg/ week methotrexate therapy and accidentally consumed 15 mg for 7 consecutive days. She was successfully treated for methotrexate toxicity and 45 days later she presented with exophytic growth on the tongue. Histopathology confirmed the diagnosis of squamous cell carcinoma and the patient underwent surgical resection. CONCLUSION: There could be a causal association between psoriasis and OSCC in the setting of acute methotrexate toxicity, as in the present case.

Transcriptomic analysis of bakanae disease resistant and susceptible rice genotypes in response to infection by Fusarium fujikuroi.

BACKGROUND: Fusarium fujikuroi causing bakanae is one of the most significant pathogens of rice and much responsible for yield losses thereby emerging as a major risk to food security. METHODS: In the present study transcriptomic analysis was conducted between two contrasting resistant (C101A51) and susceptible (Rasi) genotypes of rice with the combinations of C101A51 control (CC) vs. C101A51 inoculated (CI); Rasi control (RC) vs. Rasi inoculated (RI) and C101A51 inoculated (CI) vs. Rasi inoculated (RI). RESULTS: In CC vs. CI commonly expressed genes were 12,764. Out of them 567 (4%) were significantly upregulated and 1399 (9%) genes were downregulated. For the RC vs. RI 14, 333 (79%) genes were commonly expressed. For CI vs. RI 13,662 (72%) genes were commonly expressed. Genes related to cysteine proteinase inhibitor 10, disease resistance protein TAO1-like, oleosin 16 kDa-like, pathogenesis-related protein (PR1), (PR4), BTB/POZ and MATH domain-containing protein 5-like, alpha-amylase isozyme were upregulated in resistant genotype C101A51. Whereas, genes related to GDSL esterase/lipase, serine glyoxylate aminotransferase, CASP-like protein 2C1, WAT1-related protein, Cytoplasmic linker associated proteins, xyloglucan endotransglucosylase/hydrolase protein and ß-D xylosidase 7 were upregulated in susceptible genotype Rasi. Gene ontology analysis showed functions related to defence response (GO:0006952), regulation of plant hypersensitive type response (GO:0010363), Potassium ion transmembrane activity (GO:0015079), chloroplast (GO:0009507), response to wounding (GO:0009611), xylan biosynthetic process (GO:0045492) were upregulated in resistant genotype C101A51 under inoculated conditions. CONCLUSION: Real time PCR based validation of the selected DEGs showed that the qRT-PCR was consistent with the RNA-Seq results. This is the first transcriptomic study against bakanae disease of rice in Indian genotypes. Further, functional studies on identified genes and their utilization through different methodology will be helpful for the development of bakanae disease management strategies.

Pseudomonas aeruginosa isolate PM1 effectively controls virus infection and promotes growth in plants.

A bacterial isolate PM1 obtained from the rhizosphere of healthy plants was identified as Pseudomonas aeruginosa by biochemical characteristics and 16S rRNA gene sequence (GenBank ID OL321133.1). It induced resistance in Nicotiana tabacum cv. Xanthi-nc and Cyamopsis tetragonoloba, against Tobacco mosaic virus (TMV) and Sunn-hemp rosette virus (SRV), respectively. Foliar treatment with isolate PM1 curbed TMV accumulation in susceptible N. tabacum cv. White Burley. PM1 was more effective as a foliar than a root/soil drench treatment, evident through a comparative decrease in ELISA values, and reduced viral RNA accumulation. Foliar and soil drench treatment with PM1 resulted in a disease index of 48 and 86 per cent, and a control rate of 48.9 and 8.5 per cent, respectively. PM1 exhibited phosphate solubilization, produced siderophores, auxins, HCN, and ammonia, all important plant growth-promoting traits. Foliar treatment with PM1 enhanced growth in tobacco, while its volatiles significantly promoted seedling growth in C. tetragonoloba. Of the several metabolites produced by the isolate, many are known contributors to induction of systemic resistance, antibiosis, and growth promotion in plants. Soluble metabolites of PM1 were less effective in inducing antiviral resistance in N. tabacum cv. Xanthi-nc in comparison with its broth culture. PM1 and its metabolites were antagonistic to Gram-positive Bacillus spizizenii and Staphylococcus aureus, and fungi Fusarium oxysporum, Aspergillus niger, and Rhizopus stolonifer. Its volatiles were inhibitory to F. oxysporum and R. stolonifer. Thus, PM1 exhibited considerable potential for further evaluation in plant virus control and production of diverse metabolites of use in agriculture and medicine.

Emerging trends in immunotoxin targeting cancer stem cells.

Cancer stem cells (CSCs) are self-renewing multipotent cells that play a vital role in the development of cancer drug resistance conditions. Various therapies like conventional, targeted, and radiotherapies have been broadly used in targeting and killing these CSCs. Among these, targeted therapy selectively targets CSCs and leads to overcoming disease recurrence conditions in cancer patients. Immunotoxins (ITs) are protein-based therapeutics with selective targeting capabilities. These chimeric molecules are composed of two functional moieties, i.e., a targeting moiety for cell surface binding and a toxin moiety that induces the programmed cell death upon internalization. Several ITs have been constructed recently, and their preclinical and clinical efficacies have been evaluated. In this review, we comprehensively discussed the recent preclinical and clinical advances as well as significant challenges in ITs targeting CSCs, which might reduce the burden of drug resistance conditions in cancer patients from bench to bedside.

Abdominal wall closure in adult patients with untreated exstrophy of bladder.

INTRODUCTION: Bladder exstrophy is an anomaly, which if not treated early in the age, poses a surgical challenge in providing an adequate abdominal wall closure. We report our experience in patients with untreated exstrophy of the bladder, who underwent cystectomy, ileal conduit, and abdominal reconstruction using the anterior rectus sheath turndown flap and paired inguinal skin flaps. MATERIALS AND METHODS: Ten previously unoperated adult patients with exstrophy with epispadias, who underwent surgery at our institute from January 2010 till January 2021, were included in this study to evaluate the adequacy of abdominal wall closure with our technique of retrograde turndown anterior rectus sheath flap with paired inguinal flap, and to document immediate and delayed complications, especially incisional hernia. RESULTS: The mean follow-up period of the study was 16.5 months. We found that our technique provided adequate local tissue for a sturdy two-layered closure of the lower abdominal wall defect. Out of the ten patients, only one required an additional flap for abdominal wound closure. There were no stoma-related complications or incisional hernia. CONCLUSION: Abdominal wall reconstruction, for skin and fascial defects, in such complex cases can be performed by local skin and fascia using a relatively simple, safe, easy, and affordable technique as we have described. Our technique avoids the use of synthetic mesh, thereby reducing the chances of infection in such chronic open wounds.

Post-traumatic tuberculosis of Zygoma - An uncommon presentation.

Tubercular osteomyelitis of mid-facial bones is extremely rare because of its immense vascular supply. Due to rare incidence, myriad presentation, and lack of specific symptoms, this condition presents a challenge in diagnosis and calls for acute clinical awareness. This article presents a case report of a 31-year-old martial artist with complaints of trauma to his right malar region since one month and a gradually increasing swelling below his right eye for 3 weeks without any discharge. A diagnosis of primary Tuberculosis of right zygomatic bone was made with the help of multiple diagnostic tools. The patient was treated with four drug anti-tubercular therapy and responded with complete recovery from disease.

CSF Otorhinorrhea Due to Inner Ear Malformation-A Case Report.

Inner ear malformations are an important cause of sensorineural hearing loss ranging from severe to profound and they also contribute to Cerebrospinal fluid leakage and recurrent meningitis. The most severe is the complete labyrinthine aplasia (Michel Deformity), then there is cochlear aplasia, cochlear hypoplasia, incomplete partition of the cochlea, enlarged vestibular acqueduct and cochlear aperture abnormality.

A comparison of induced antiviral resistance by the phytoprotein CAP-34 and isolate P1f of the rhizobacterium Pseudomonas putida.

CAP-34 is a previously reported phytoprotein isolated from Clerodendrum aculeatum (syn. Volkameria aculeata), inducing systemic antiviral resistance against plant virus infection in susceptible plants. This paper compares the resistance inducing efficacy of CAP-34 and a rhizobacterial isolate P1f on tomato (systemic) and tobacco Xanthi-nc (hypersensitive), against tobacco mosaic virus (TMV). The PGPR isolate was identified as an isolate of Pseudomonas putida through molecular and biochemical characterization, and it exhibited PGPR traits such as production of auxin and siderophore. GC-MS examination of the volatiles produced by P1f included several that are implicated in antimicrobial activity, growth promotion and induced systemic resistance. Foliar treatment of tobacco plants with P1f and CAP-34 led to an induced antiviral state in hypersensitive tobacco that persisted for 5 and 3 days, post-treatment, respectively, with a percent reduction in lesion number greater than 90. A higher accumulation of hydrogen peroxide and production of peroxidase enzyme was recorded in P1f-treated leaves, in comparison to those with CAP-34 treatment. The disease incidence in tomato plants treated with CAP-34 and P1f was 30 and 60 percent, respectively, 28dpi. A significant increase was noted in growth parameters such as number of branches and flowers in CAP-34 treated plants, while a significant enhancement in plant height and dry shoot and root weight was observed in P1f-treated set, compared to the control set. ELISA values for the presence of TMV were significantly lower in the infected tomato plants in the treated sets, as compared to the control set, with CAP-34 treatment exhibiting better results as against the P1f-treated set. In the resistant plants from either set, no viral RNA or viral coat protein was detected through RT-PCR and serology. These results suggest that CAP-34 affords more pronounced protection against virus infection compared to the rhizobacterial isolate P1f.

Tendoachilles reconstruction and overlying skin cover with a peroneus brevis flap.

We report a post-traumatic case of tendoachilles injury with an overlying skin defect. Following debridement, tendon reconstruction was done by using vascularised peroneus brevis musculotendinous unit and proximal part of the same muscle provided the skin cover. Postoperative recovery was uneventful. At 2 years follow-up, he had a near-normal gait. The main advantage of this flap is not being only a local flap but also providing a vascularised tendon.

Pulmonary sclerosing pneumocytoma masquerading adenocarcinoma with co-existing BRAF V600E and PTEN mutation.

We report a case of a massive primary sclerosing pneumocytoma (PSP) involving the right lower lobe adhering esophagus with small synchronous PSP on the superior segment of the left lower lobe with concurrent mutation for B-RAF proto-oncogene, serine/threonine kinase (BRAF V600E), and phosphatase and tensin homolog (PTEN) gene in a young female. She underwent right lower lobectomy and mediastinal lymph node dissection under single lung ventilation with tumor-free margins on diagnosis-based findings of preoperative computed tomography-guided biopsy and positron emission tomography. Histopathology was suggestive of PSP-papillary variant with concurrent mutation of BRAF V600E and PTEN genes. Post-operative follow-up at four weeks was uneventful. She has to undergo wedge resection for the contralateral disease after six weeks following recovery from the first surgery.

Proteomics of Sentinel Lymph Nodes in Early Breast Cancer for Identification of Thymidylate Synthase as a Potential Biomarker to Flag Metastasis: A Preliminary Study.

INTRODUCTION: Breast cancer is the second most common cancer in women across the world. Some of the patients who present in the early stage of disease are affected by metastasis to the axillary group of lymph nodes. The first among this group that is affected is called as sentinel lymph node, and its diagnosis is crucial for the staging of cancer thereby dictating the type of surgical therapy. Therefore, the sentinel lymph node status provides the most relevant information to the surgeon and patient prognosis. The expanded utilization of breast conservation surgery has declined the morbidity associated with mastectomy and axillary lymph node surgery. Recent interest is, therefore, centered on techniques that allow accurate assessment of the sentinel lymph node metastasis. A current procedure such as sentinel lymph node biopsy (SLNB) that is used to assess axillary lymph node metastasis is neither specific nor sensitive, and besides, it is time-consuming. OBJECTIVE: To compare the protein profiles between metastatic and non-metastatic lymph nodes to identify a biomarker that can flag lymph node metastasis. MATERIALS AND METHODS: Women with early breast cancer were screened using mammography imaging and recruited to the study. Surgical resection was done to remove the breast tissue, and sentinel lymph node was identified using fluorescein and methylene blue tracer. Lymph node was sliced, and one set was sent for histopathology, which was considered the gold standard to assess the metastatic status of the lymph node. One set of slices was taken for proteomic experiments. Proteins were labelled with fluorescent cyanine tags and were subjected to difference gel electrophoresis experiment. Differentially expressed spots that had at least a twofold relative ratio and consistent pattern across three sets of biological replicate experiments were marked. Gel spots were trypsin digested and identified on mass spectrometry machine. Validation study was done by Western blot experiment on the same set of samples. RESULTS: Thymidylate synthase has a twofold higher expression in the metastatic sentinel lymph nodes as compared to non-metastatic lymph nodes in early breast cancer patients. CONCLUSION: Differential in gel expression proteomics is an ideal platform for the identification of potential protein biomarker candidates that can differentiate metastatic from non-metastatic lymph nodes in early breast cancer. The identification of thymidylate synthase offers a scope to develop an on-table diagnostic kit to assess the status of sentinel lymph nodes during mastectomy procedure to guide surgical management of axillary lymph nodes in early breast cancer.

Marjolin Ulcer: An Observational Epidemiological Study From a Tertiary Care Centre in India.

INTRODUCTION: Marjolin ulcer is a rare skin malignancy. Marjolin ulcer arises in zones of long-standing scars, inflammation, or chronic wounds. MATERIAL AND METHODS: The present study was conducted to assess the demographic profile and identify the predictors of recurrence in 55 patients with Marjolin ulcer admitted over 10 years. Patients underwent either wide local excision with 2-cm peripheral margin or amputation if clinically indicated due to joint involvement. Lymph nodes were dissected if found positive. Patients received adjuvant radiotherapy if tumor clearance was less than 4 mm or the draining lymph nodes were positive. RESULTS: Of the total 55 cases (mean age, 48.75 years; range, 24-74 years), 34 were men and 21 were women (male/female, 1.6:1). The most common cause of injury was flame burn (n = 32, 58%) followed by trauma (n = 10, 18%). The lower limb was frequently affected (n = 38, 69.1%). Twenty-six patients with resection margins less than 4 mm had received adjuvant radiotherapy. Among the 55 patients, 6 (11%) had undergone lymph node dissection. Local recurrence was noted within 18 months in 9 (16.35%) patients, of which 5 patients had a tumor-free margin of less than 4 mm. We found 2 predictors for local recurrence. First, moderately differentiated squamous cell carcinoma (P = 0.04) and, second, patients with lymph node involvement (P = 0.001). CONCLUSION: Marjolin ulcer is a high-risk skin tumor. Patients with positive lymph node or with moderately differentiated squamous cell carcinoma have high chances of recurrence. Frequent and intense follow-up is required for at least 2 years.

Distally based peroneus brevis muscle flap: A single centre experience.

PURPOSE: Defects around the distal one third of the leg and ankle are difficult to manage by conservative measures or simple split thickness skin graft. Distally based peroneus brevis muscle flap is a well described flap for such defects. METHODS: This is a retrospective analysis conducted on 25 patients with soft tissue and bony defects of distal third of lower leg and ankle, which were treated using distally based peroneus brevis muscle flap from January 2013 to January 2018. Information regarding patient demographics, etiology, size and location of defects and complications were collected. All patients were followed up for at least 3 months after surgery. RESULTS: There were 21 males and 4 females with the mean age of 39 (5-76) years. The most common cause of injuries was road traffic accident, followed by complicated open injury. The average size of defects was 20 (4-50) cm2. The mean operating time was 75 (60-90) min for flap harvest and inset. We had no patient with complete loss of the flap. Five patients (20%) had marginal necrosis of the flap and two patients have graft loss due to underlying hematoma and required secondary split thickness skin grafting. CONCLUSION: The distally based peroneus brevis muscle flap is a safe option with reliable anatomy for small to moderate sized defects following low velocity injury around the ankle. The commonest complication encountered is skin graft loss which can be reduced by primary delayed grafting.

Graciloplasty for Anal Incontinence-Is Electrical Stimulation Necessary?

INTRODUCTION: Anal incontinence brings lot of social embarrassment, mental distress, dignity loss, anxiety, low confidence, and eventually a low self-esteem with a restricted social life to the affected person. Surgical repair is the mainstay of treatment for anal incontinence. However, some patients need additional procedures such as gluteoplasty, graciloplasty (adynamic and dynamic), artificial bowel sphincter, and sacral nerve stimulation, which help to reinforce or augment the anal sphincter. METHODS: A retrospective analysis of 17 patients who underwent adynamic graciloplasty for reconstruction of anal sphincter from January 2008 to December 2017 was done. Demographic profile, fecal incontinence scores (Wexner score and KAMM score), and anal manometric findings were recorded pregraciloplasty and postgraciloplasty. RESULTS: Of the total 17 patients, 9 were males and 8 were females. Satisfactory continence was achieved in 13 patients out of 17 (76.47%). Continence was defined as satisfactory for patients having a postoperative Wexner score of 2 or less and KAMM score of 4 or less. It was considered to be poor if the Wexner score was greater than 6 and KAMM score was greater than 8 in the follow-up period or if the stoma was not reversed. CONCLUSIONS: Unstimulated or adynamic graciloplasty is a relatively safe procedure, has a short learning curve, is affordable, and avoids the additional implant-related complications. We feel that the unstimulated graciloplasty still has a significant role in the management of anal incontinence.