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Structurally diverse fused polycyclic pyrrolo[3,2-c]quinolinone/pyrrolizino[2,3-c]quinolinone hybrids were synthesized to get excellent yields via a tandem multi-component reaction sequence employing an environmentally benign solid state melt reaction involving [3+2]-cycloaddition process followed by two consecutive annulation steps. Baylis–Hillman products, used as dipolarophiles, were synthesized from various substituted aryl/heteroaryl aldehydes in the presence of DABCO and methyl acrylate, while the 1,3-dipole component was derived in situ from indoline-2,3-dione and acyclic/cyclic amino acid viz N-methylgylcine/l-proline. The structure of the unusual tandem products was unambiguously assigned by spectroscopic and XRD analysis. The products arose through the formation of three new rings, five new bonds, and three adjoining stereocenters with complete diastereomeric control.

* Context.--Molecular analysis of poorly differentiated/ undifferentiated sinonasal neoplasms has resulted in identification of a growing number of genetically defined tumors. SMARCA4-deficient sinonasal carcinoma is one such recently described entity that emerged from within sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and teratocarcinosarcoma (TCS). Objective.--To identify SMARCA4-deficient sinonasal carcinomas from a large institutional cohort of poorly differentiated/undifferentiated carcinomas and evaluate their clinicopathologic features. Design.--SMARCA4/BRG1 immunohistochemistry was performed on all tumors diagnosed as SNUC, poorly differentiated carcinoma, NEC, and TCS during a 12-year period. SMARCA2/BRM and INSM1 immunostaining was performed in SMARCA4-deficient cases. Results.--Twelve SMARCA4-deficient sinonasal carcinomas were identified among 299 cases. Morphologically, 5 cases were large cell NEC, 2 cases were small cell NEC, and 5 were TCS. SMARCA4 loss was diffuse and complete in 10 cases, while 2 cases showed focal retention. Most cases showed diffuse cytokeratin staining accompanied by weak, usually focal staining for chromogranin and synaptophysin. INSM-1 showed negativity in most cases. All cases showed retained SMARCA2 expression. IDH1/2 mutation was absent in all cases analyzed. Four of 7 patients died of disease, and aggressive multimodality treatment provided better outcome. Conclusions.--SMARCA4-deficient sinonasal carcinomas are morphologically akin to sinonasal poorly differentiated NECs and TCS, display cytokeratin positivity and only focal staining for neuroendocrine markers, and have aggressive biological behavior. Inclusion of SMARCA4 in the immunohistochemical panel for diagnostic workup of all sinonasal NEC and TCS phenotypes will facilitate their early recognition. Comprehensive germline and somatic mutational analyses of these tumors are necessary for further insights into their molecular pathogenesis. (Arch Pathol Lab Med. 2022;146:1122-1130; doi: 10.5858/arpa.2021-0001-OA), The sinonasal tract harbors a diverse spectrum of high-grade neoplasms, many of which have considerable overlapping morphologic features owing to their poorly differentiated or undifferentiated appearance. (1,2) Some of these [...]

Objective: To determine if systemic administration of low-molecular-weight heparin impacts venous compromise in loco-regional flap reconstruction for head and neck subsites. Methods: This prospective study was conducted on patients who had developed features of venous compromise of the flap. The case group received low-molecular-weight heparin (dalteparin). Results: Of the 73 patients who developed venous congestion, low-molecular-weight heparin was administered in 47 patients. In the low-molecular-weight heparin subset, 23 patients had either reversal or non-progression of venous compromise (48.9 per cent). Of the patients who had no response to low-molecular-weight heparin rescue, complete necrosis was seen in 4 and partial flap necrosis was observed in 19. The corresponding numbers in the control group were 13 and 12, respectively (odds ratio 23.9, p = 0.002). Additionally, the low-molecular-weight heparin arm had a lower incidence of partial or complete flap necrosis (p = 0.002). Conclusion: Low-molecular-weight heparin salvage, when instituted early, is likely to result in a significant reduction in flap-related morbidity. [ABSTRACT FROM AUTHOR]

The present study is to identify polycyclic aromatic bioactive phytocompounds from Eclipta alba against breast cancer target protein through in silico approach. Among 52 phytocompounds ecliptalbine, wedelolactone, ursolic acid and beta amyrin they have exhibited strong binding affinity against all three screened breast cancer target proteins such as matrix metallo protein (PDB ID 1RM8), estrogen receptor (PDB ID 3ERT) and progesterone receptor (PDB ID 4OAR). In drug likeliness 11 phytocompounds showed zero violations against all five drug likeliness rule, whereas all three anticancer drugs showed three minimal violations against the drug likeliness rule. Docking score of all screened compounds lies in the range of −4.3 Kcal/mol to −9.4 Kcal/mol in that ecliptalbine and ursolic acid show maximal binding affinity with all screened target proteins of breast cancer. Phytocompound ecliptalbine, wedelolactone and ursolic acid has shown excellent simulation trajectories with two screened target proteins in MDS analysis. Further compound ecliptalbine shown good phracokinetic and DFT scores which affirm that reason behind the good binding affinity with breast cancer target proteins. MMGBSA analysis also affirms the excellent binding affinity of ecliptalbine with breast cancer target proteins (–51.42 and −72.74 Kcal/mol) than the standard drug score. Finally ethanolic leaf extract of Eclipta alba showed excellent In vitro antioxidant (DPPH-IC50 83.40 µg/ml and ABTS–IC50 48.80 µg/ml) and cytotoxic potential (IC50 97.20 µg/ml) against triple-negative breast cancer cells (MDA-MB-231). Further these drug candidates can be validated through in vitro and preclinical studies to discover novel drug for breast cancer therapeutics. [ABSTRACT FROM AUTHOR]

Background: There exists a lacuna in the structured reporting of swallowing dysfunction and quality of life (QoL) outcome following major glossectomy. Methods: Prospective cohort study to assess the swallowing dysfunction and QoL following STG (subtotal glossectomy) or NTG (near total glossectomy) over a 6‐month period using FEES and PAS scale, MDADI, and FACT‐HN. Results: Twenty‐four patients were available for analysis. The pre‐ and post‐adjuvant evaluation revealed a statistically significant improvement in the composite MDADI and FACT‐HN scores. Subscale analysis of FACT‐HN scores revealed maximum deficit in the head and neck cancer‐specific score domain followed by functional domain and social well‐being domain, with serial improvement noted in the post‐adjuvant setting. Conclusion: This study showed serial improvement in terms of swallowing dysfunction although social and functional well‐being domains related to QoL continued to reveal major deficits. Better outcomes were seen with preservation of bilateral base of tongue and mandible. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to identify factors predicting outcomes following pectoralis major myocutaneous flap reconstruction in complex oromandibular defects. Methods: A prospective cohort study was conducted at a tertiary care oncology center in South Asia from January 2020 to May 2022 to include consecutive cases of complex oromandibular defects reconstructed with pectoralis major myocutaneous flap. During pectoralis major myocutaneous flap harvest surgical modifications were incorporated to preserve the choke vessel from the fourth intercostal perforator and lateral pedicle supply apart from the main pedicle from acromiothoracic artery. Results: In our series of 196 patients, overall flap compromise was noted in 17.6% with the most common pattern of failure being partial fullthickness necrosis (n = 23) and complete flap loss was identified in only 3 cases. The factors that showed statistically significant correlation with flap outcome in the univariate model were female sex (42.9% vs. 14.9%) associated with a higher incidence of flap compromise, while bipaddle pectoralis major myocutaneous flap (2.2% vs. 17.3%) and larger surface area of skin paddle (>49 cm²) (20.2%, 16%, and 0% in <49 cm², 50-96 cm², and >96 cm², respectively) were factors favoring a better outcome. Factors that emerged as independent prognostic variables in the multivariate model were female sex (odds ratio: 9.801, P = .001) and high body mass index (odds ratio: 1.19, P = .03) signifying a higher incidence of flap compromise. Conclusion: Pectoralis major myocutaneous flap is still the "workhorse" of head and neck reconstruction. Nevertheless, the female sex and high body mass index may serve as deterrents to the success of this flap. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the effect of quadriceps isometric exercises along with hip abductors isometric exercises as integrated exercise with quadriceps exercises in reducing pain, disability in medial knee osteoarthritis. The Total of 54 patients (both male and female) were recruited in this study but on the basis of inclusion and exclusion criteria, only 32 were included in this study. Womac index was opted as outcome measures to collect the data of pain, disability and functional limitation. Participants were randomly assigned to integrated exercise group; (n = 16) (mean age 52) who performed exercises [Quadriceps isometric along with hip abductor isometric exercises] and quadriceps isometric exercises group (n = 16) (mean age 49) performed for 3 weeks. 32patients were analyzed and the effect of integrated exercises [Quadriceps isometric along with hip abductor isometric exercises] showed a statistically significant difference in pain, disability and functional limitation (p < 0.000). Total duration to collect the pre and post data of pain, disability and functional limitation was 3 weeks. 3 weeks of exercise protocol was effective in both groups in terms of reducing pain and disability but integrated exercises were found to be more effective than quadriceps exercise in improving the pain, disability and functional limitation over the time at the level of significance. [ABSTRACT FROM AUTHOR]