Anatomic Subunit Cleft Lip Repair: New Repair Concept Based on Nostril Sill and Philtrum-White Roll Junction.

A novel method for unilateral cleft lip repair based on lip anatomic subunits was presented in 2005 by David M. Fisher. It has about 25 landmarks with 2 arbitrary markings for the nostril. It is an important subunit when it comes to nose reconstruction. This article sheds light on the variance in nostril sill disposition among cleft lip patients. A novel marking technique based on differences in sills is presented. Furthermore, the unique anatomical structure of the philtrum-white roll junction is highlighted with a suggested modification to the subunit approximation leading to its reconstitution.

BRAF V600E in a preclinical model of pleomorphic Xanthoastrocytoma: Analysis of the tumor microenvironment and immune cell infiltration dynamics in vivo.

Low-grade glioma (LGG) is the most common brain tumor affecting pediatric patients (pLGG) and BRAF mutations constitute the most frequent genetic alterations. Within the spectrum of pLGGs, approximately 70%-80% of pediatric patients diagnosed with transforming pleomorphic xanthoastrocytoma (PXA) harbor the BRAF V600E mutation. However, the impact of glioma BRAF V600E cell regulation of tumor-infiltrating immune cells and their contribution to tumor progression remains unclear. Moreover, the efficacy of BRAF inhibitors in treating pLGGs is limited compared with their impact on BRAF-mutated melanoma. Here we report a novel immunocompetent RCAS-BRAF V600E murine glioma model. Pathological assessment indicates this model seems to be consistent with diffuse gliomas and morphological features of PXA. Our investigations revealed distinct immune cell signatures associated with increased trafficking and activation within the tumor microenvironment (TME). Intriguingly, immune system activation within the TME also generated a pronounced inflammatory response associated with dysfunctional CD8+ T cells, increased presence of immunosuppressive myeloid cells and regulatory T cells. Further, our data suggests tumor-induced inflammatory processes, such as cytokine storm. These findings suggest a complex interplay between tumor progression and the robust inflammatory response within the TME in preclinical BRAF V600E LGGs, which may significantly influence animal survival.

Revisiting Elliot's Modification of Moberg's Flap and Our Improvisation.

Thumb tip injuries constitute one of the most common hand injuries. There are various reconstructive options for thumb tip injuries. We present our series of thumb tip injuries reconstructed using Elliot's modification of the Moberg flap, which provides like-for-like tissue. We also present our flap improvisation, which can be useful in the armamentarium of plastic surgeons. Background Moberg described the advancement flap for thumb defects in 1964, which was modified by O'Brien in which the proximal part of the flap is incised and advanced. Although it is a popular flap, it has the disadvantage of interphalangeal (IP) joint flexion deformity. Among the various modifications of the Moberg flap, Elliot's flap provided more tissue with minimal donor site morbidity and no usage of skin grafts or first web skin. Methods We retrospectively analyzed the patients who underwent reconstruction of thumb defects by Elliot's modified Moberg's flap. The size of the defect, etiology, and IP joint movement were analyzed. Two patients underwent our improvised flap where a daughter flap was elevated within Elliot's flap. Results Between January 2021 and September 2023, 12 patients underwent reconstruction by Elliot's flap. All flaps settled well. There was no IP joint deformity. Two patients had scar hypertrophy that was managed conservatively. Conclusion Elliot's modification of the Moberg flap is a very useful but underutilized flap for thumb tip injuries that provides like tissue with sensation and with little donor site morbidity. It can be used for thumb tip defects of up to 3 cm . It is possible to incorporate a second V-Y flap in patients for whom additional movement is required for tension-free closure.

Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma.

PURPOSE: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax. PATIENTS AND METHODS: In this study, we report the findings of four patients enrolled onto the NeoVax clinical trial (NCT0342209). RESULTS: Immune reactivity to NeoVax neoantigens was assessed in peripheral blood mononuclear cells pre- and post-NeoVax for patients 1 to 3 using IFNγ-ELISPOT assay. A statistically significant increase in IFNγ producing T cells at the post-NeoVax time point for several neoantigens was observed. Furthermore, a post-NeoVax tumor biopsy was obtained from patient 3 and, upon evaluation, revealed evidence of infiltrating, clonally expanded T cells. CONCLUSIONS: Collectively, our findings suggest that NeoVax stimulated the expansion of neoantigen-specific effector T cells and provide encouraging results to aid in the development of future neoantigen vaccine-based clinical trials in patients with GBM. Herein, we demonstrate the feasibility of incorporating multisector sampling in cancer vaccine design and provide information on the clinical applicability of clonality, distribution, and immunogenicity of the neoantigen landscape in patients with GBM.

Applications and Reliability of Dorsal Metacarpal Artery Perforator Flap.

Dorsal metacarpal artery perforator flap (DMAP), first described by Quaba and Davison, is a useful tool in the armamentarium of plastic surgeons. It provides like for like tissue for the reconstruction of dorsal finger defects. It is a simple and relatively easy flap to harvest with minimal donor site morbidity. In this case series, we present our experience, applications, and surgical technique of flap harvesting.

Assessing the Accuracy of Common Clinical Tests for Detecting Palmaris Longus: A Prospective Study in a Tertiary Center.

Background Palmaris longus (PL) is a short-bellied muscle with a long tendon that merges with the palmar aponeurosis. It is supplied by the median nerve and acts as a tensor of the palmar aponeurosis and flexes the wrist. This tendon is commonly used for tendon transfers and as a donor for tendon graft. There are numerous clinical tests to detect the presence of PL like Schaeffer's test, Thompson's test, Mishra's test I, Mishra's test II, Pushpakumar's "two-finger sign" method, and AIIMS test. The principle of all these tests is to make the tendon prominent by eliciting its flexor action and then its identification by inspection and palpation. Objectives The tests that are consistently easy to perform with good understandability would be easy to explain to the general population (patients). The aim of our study is to find out the accuracy and easy comprehensibility of various tests using compulsive postures for detecting PL tendon clinically. Materials and Methods This is a prospective study on 137 participants. All the patients were subjected to six clinical tests to detect the presence or absence of PL tendon. The results were recorded for both hands by a single observer. Results Of the 137 participants, 75 were males (54.74%) and 62 were females (45.26%). The mean age was 21 years. The AIIMS test showed the maximum number of tendons, that is, 113 (82.4%) in the right hand and 108 (78.8%) in the left hand. In view of the ability to comprehend the tests, 119 (86.9%) subjects understood Schaeffer's test very easily. Conclusion According to this study, the AIIMS test best demonstrates the PL tendon, and Schaeffer's test was the test most easily understood by the subjects.

Combined preauricular, retroauricular bilobed flap for earlobe reconstruction.

The earlobe is an important anatomical structure that has a significant role in aesthesis. An absent ear lobule may be congenital or acquired due to the result of trauma, infection or malignancy. Its surgical repair places a challenge due to the difficulty of obtaining a natural-appearing and durable outcome. Many procedures have been described for reconstruction including the Gavello and Zenteno Alanis techniques. We have described a new method which is single staged, easy to perform and aesthetically acceptable.

Feasibility of Laterocaudal Approach in Comparison with Subtarsal Approach in the Management of Orbital Rim Fractures in Indian Population: A Prospective Study.

A balance between surgical access and aesthetics, with lesser post-op sequelae, is inevitable in the management of facial fractures. Even though various approaches are widely practised, further modifications and revisions are encouraged for better outcomes. We performed a prospective cross-sectional study on 30 patients with Zygomatico-Maxillary Complex (ZMC) fracture with inferior orbital rim involvement. Surgical management was performed using subtarsal (Group A) or laterocaudal (Group B) approach, during which the time taken to expose fracture and the ease of access was documented. Scar evaluation was performed using SCAR Scale on the 15th day and after one-month and three-month follow-up, and the post-op complications including ectropion, infections, edema, etc., were documented. There was a significant reduction in the time taken (p < 0.001) in group B than in group A. The ease of access did not demonstrate any significant difference. The SCAR scale score was significantly reduced at 3rd-month follow-up in group B compared to the other group (p = 0.009). Laterocaudal approach demonstrated lesser time-taken and better access to the inferolateral rim, with superior aesthetics and fewer complications. This approach can be employed in clinical practice, especially with inferolateral rim involvement in ZMC fractures.

Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 virus-specific cytotoxic T-cell lymphocytes (vCTLs) could provide a promising modality in COVID-19 treatment. We aimed to screen, manufacture, and characterize SARS-CoV-2-vCTLs generated from convalescent COVID-19 donors using the CliniMACS Cytokine Capture System (CCS). METHODS: Donor screening was done by stimulation of convalescent COVID-19 donor peripheral blood mononuclear cells with viral peptides and identification of interferonγ (IFN-γ)+ CD4 and CD8 T cells using flow cytometry. Clinical-grade SARS-CoV-2-vCTLs were manufactured using the CliniMACS CCS. The enriched SARS-CoV-2-vCTLs were characterized by T-cell receptor sequencing, mass cytometry, and transcriptome analysis. RESULTS: Of the convalescent donor blood samples, 93% passed the screening criteria for clinical manufacture. Three validation runs resulted in enriched T cells that were 79% (standard error of the mean 21%) IFN-γ+ T cells. SARS-CoV-2-vCTLs displayed a highly diverse T-cell receptor repertoire with enhancement of both memory CD8 and CD4 T cells, especially in CD8 TEM, CD4 TCM, and CD4 TEMRA cell subsets. SARS-CoV-2-vCTLs were polyfunctional with increased gene expression in T-cell function, interleukin, pathogen defense, and tumor necrosis factor superfamily pathways. CONCLUSIONS: Highly functional SARS-CoV-2-vCTLs can be rapidly generated by direct cytokine enrichment (12 hours) from convalescent donors. CLINICAL TRIALS REGISTRATION: NCT04896606.

Distichiasis: An Unusual Complication of the Preseptal Transconjunctival Approach and Its Management.

ABSTRACT: Distichiasis is a rare condition where the accessory row of eyelashes exit from the posterior lid margin apparently from the opening of the meibomian glands, causing corneal irritation and ulceration. The authors report a rare clinical presentation of acquired distichiasis, as a complication of a preseptal transconjunctival approach. The patient presented with complaints of discomfort over the right eyelid after the management of zygomaticomaxillary complex fracture. On evaluation, the diagnosis of acquired distichiasis was made and was surgically managed by direct tarsal strip excision. During the follow up the complete resolution of symptoms without lid margin deformity was noted. Acquired distichiasis as a complication of the preseptal transconjunctival approach was rarely reported. Hence the understanding of the condition and its management is necessary to avoid the sequela.

The Syntheses and Medicinal Attributes of Phenanthrenes as Anticancer Agents: A Quinquennial Update.

Cancer is a silent killer and remains to pose major health problems globally. Amongst the several biological targets, DNA is one of the most striking targets in cancer chemotherapy. Owing to its planar structure, phenanthrene and its derivatives exhibit potential cytotoxicity by intercalating between the DNA base pairs and by inhibiting the enzymes that are involved in the synthesis of DNA. However, due to the off-target effects and resistance, the development of novel chemotherapeutic agents would be meritorious. In this regard, we present a detailed review on the development of phenanthrene-based derivatives reported in the last quinquennial. This review mainly focuses on the synthetic aspects and strategies to procure the fused phenanthrene derivatives such as (i) phenanthroindolizidines, phenanthroquinolizidine, phenanthroimidazoles, podophyllotoxin-based phenanthrenes, and dihydrophenanthrodioxine derivatives, (ii) phenanthrene conjugates with other pharmacologically significant pharmacophores, and (iii) phenanthrene-metal complexes. This review also edifies their potential in vitro cytotoxicity evaluation against various carcinoma cell lines in submicromolar to nanomolar ranges. Additionally, computational studies and structure-activity relationships (SARs) have also been presented to highlight the essential features of the designed congeners. Thus, this review would aid in the development of novel derivatives in future as potential cytotoxic agents in the field of medicinal chemistry.

Vernonia cinerea regenerates tubular epithelial cells in cisplatin induced nephrotoxicity in cancer bearing mice without affecting antitumor activity.

BACKGROUND: Traditional Siddha Medicine advises using metal-based formulations to treat cancers. In the case of any toxicities during the therapy, Siddha physicians use Vernonia cinerea (VC) whole plant kashayam (crude aqueous extract-CAE) to reverse the toxic effects. AIM: To evaluate the nephroprotective activity of CAE and its fractions in cisplatin-induced nephrotoxicity and to assess whether they compromise the anticancer efficacy of cisplatin. MATERIALS AND METHODS: Cisplatin-induced renal damage was induced in Ehrlich Ascites Carcinoma (EAC) bearing mice during mild phase of tumor growth. CAE and its butanol (BF) and aqueous (AF) fractions were administered orally from the 5th day for five days. Nephroprotective potential (serum urea, creatinine, renal histology) and effect of VC on cisplatin anticancer efficacy (tumor volume, viable tumor cells, percentage increase in life span (% ILS)) were calculated. RESULT: CAE and its fractions significantly reversed the cisplatin-induced renal damage. CAE and BF treated animals showed regeneration of 50%-75% of proximal tubular cells. Compared to EAC control mice, the % ILS of the cisplatin-treated group was 244% and it was further extended to 379% after CAE administration. The % ILS in the CAE treated group was 1.6 times higher than the cisplatin alone treated group. GC-MS study showed the presence of astaxanthin and betulin. CONCLUSION: CAE of VC reverses cisplatin-induced kidney damage as well as regenerates proximal tubular epithelial cells, without compromising the anticancer effect of cisplatin. When CAE was further fractionated, the nephroprotective activity was retained, but the beneficial anticancer effect of cisplatin was compromised.

Traditional Versus Virtual Surgery Planning of the Fronto-Orbital Unit in Anterior Cranial Vault Remodeling Surgery.

BACKGROUND: Craniosynostosis correction surgery is a complex procedure, which involves complete dismantling and reassembly of the cranial vault components. The traditional planning method for these surgeries results in increased intra-operative time owing to its highly subjective nature. The advent of virtual surgical planning (VSP) platform has lead to a greater pre-operative insight and precision outcome in calvarial remodeling surgeries. The purpose of this paper is to evaluate intra-operative time and blood loss difference as a measure of surgical efficiency between VSP based template guided Anterior Cranial Vault Reconstruction (ACVR) with Fronto-Orbital Unit Advancement (FOUA) and the traditional surgeries. METHODS: Data were collected from patients who underwent ACVR with FOUA in our unit. Patients were divided into 2 groups, Template Fronto-Orbital Unit (TFOU) group and Non-template Fronto-Orbital Unit (NFOU) group. In TFOU group, Virtual planning along with fabrication of Template guide was carried out. Patients undergoing ACVR using traditional techniques were categorized as NFOU group. A comparative prospective analysis was carried out in terms of Intra-operative time duration and blood loss. Student 't' test was used to compare the means of the 2 groups. RESULTS: A total of 10 patients were included in the present study. There were 5 control (NFOU) and 5 TFOU cases. There was a significant decrease in the operating time in TFOU group compared to the NFOU group. TFOU group also showed reduced intra-operative bleed compared to the NFOU group. CONCLUSION: Virtual surgical planning (VSP) and 3D modeling with prefabricated template guide augurs reliable outcomes and portends the possibility of lesser intra-operative time. It is a valuable tool, which offers enormous benefits in terms of precise pre-surgical planning with predictive results.

Discovery of Natural Product Derived Labdane Appended Triazoles as Potent Pancreatic Lipase Inhibitors.

Obesity contributes to the genesis of many metabolic disorders including dyslipidemia, coronary heart disease (CHD), nonalcoholic fatty liver, type 2 diabetes, etc. Pancreatic lipase plays a vital role in food fat digestion and absorption. Therefore, to control obesity, inhibition of pancreatic lipase is the active therapy. Thus, novel natural product derived labdane appended triazoles with pancreatic lipase inhibition potential were designed and synthesized. Among these hybrids, 6b and 6f exhibited excellent inhibitory activity (IC50 0.75 ± 0.02 µM and 0.77 ± 0.01 µM), slightly better than that of the positive control Orlistat (IC50 0.8 ± 0.03 µM). Compounds 6c, 6e, and 6g-j inhibited the PL comparable to that of positive control. Interestingly none of the compounds showed cytotoxicity (Hep G2) in the concentration range from 0.5 to 100 µM. Overall results reveal the potential of labdane appended triazoles as antiobesity agents.

Large Eccrine Acrospiroma of the Hand.

Eccrine acrospiroma are benign skin tumours of sweat duct origin. They usually present as small solid or cystic lesions which are confused clinically with other solid or cystic lesions. These are generally benign lesions with few reports of malignant transformation. Here, we report a case of a middle aged female presenting with a swelling of the dorsum of left first web space which was histopathologically diagnosed as an eccrine acrospiroma, which was managed with surgical excision and covered with a regional flap. This case is presented due to the large size of the lesion in the hand.

Superficial Acral Fibromyxoma: A Rare Entity - A Case Report.

Superficial acral fibromyxoma (SAF) is a rare lesion initially described by Fetsch as a tumour with histological and immunohistochemical features located at acral sites. It is a benign slow-growing soft tissue lesion occurring in males. Patients generally look for late medical help as it is generally painless. The lesion consists of spindled and stellate-shaped cells in the myxocollagenous stroma with immunohistochemical positivity for CD34, CD99 and vimentin. Treatment is surgical excision with regular follow-up. Here we present a case of a superficial acral fibromyxoma of the left index finger which radiologically showed features of vascular anomaly on MRI. The lesion was surgically excised and histopathology revealed features suggestive of superficial fibromyxoma with positive immunohistochemistry for CD34 and negative for S-100.

Sebaceous Gland Carcinoma of the Lower Eyelid Reconstructed with a Composite Flap: A Case Report.

Sebaceous gland carcinomas are skin adnexal tumours occurring in the periocular region of elderly females. It is an uncommon malignancy usually involving the upper eyelid and has an indolent course. Mainstay of treatment is surgical excision. Here we present a case of a sebaceous gland carcinoma of the lower eyelid for which wide local excision was done and the lower eyelid reconstructed using a composite flap of nasal chondromucosal graft with a nasolabial flap.

Macrodystrophia Lipomatosa of the Toe: A Rare Case Report.

Macrodystrophia lipomatosa is a rare congenital hamartoma presenting as a localized or generalized gigantism of a limb or digit manifesting from infancy to late adulthood. It is a progressive enlargement of the soft tissue components, especially fibrofatty tissue. The patient presents to us because of cosmetic reasons or mechanical issues secondary to degenerative joint disease, or features of neurovascular compression due to large osteophytes. Here, we present a case of this anomaly of the left second toe with complaints of difficulty in walking and wearing shoes, for which toe reduction surgery with partial amputation was done.

Malignant Proliferative Trichilemmal Tumour of The Nape of The Neck - A Case Report.

Proliferating trichilemmal tumours are benign but locally aggressive tumours arising from the hair follicle. They are biologically benign lesions, but may be locally aggressive. They are generally solitary lesion and commonly occurring in the scalp of elderly women. Malignant transformation has been known to occur but very rarely. Here we report a rare case of a recurrent malignant trichilemmal tumour of the scalp in a middle aged male which was surgically excised.

Synaptic Plasticity and Neurological Disorders in Neurotropic Viral Infections.

Based on the type of cells or tissues they tend to harbor or attack, many of the viruses are characterized. But, in case of neurotropic viruses, it is not possible to classify them based on their tropism because many of them are not primarily neurotropic. While rabies and poliovirus are considered as strictly neurotropic, other neurotropic viruses involve nervous tissue only secondarily. Since the AIDS pandemic, the interest in neurotropic viral infections has become essential for all clinical neurologists. Although these neurotropic viruses are able to be harbored in or infect the nervous system, not all the neurotropic viruses have been reported to cause disrupted synaptic plasticity and impaired cognitive functions. In this review, we have discussed the neurotropic viruses, which play a major role in altered synaptic plasticity and neurological disorders.