Minimal Necrosis Research Articles

Histopathological Assessment of Tricalcium Aluminate-free Mineral Trioxide Aggregate and Two Antibacterial Enhanced Mineral Trioxide Aggregates As Pulpotomy Agents in Rat Model.

To evaluate the effect of a newly developed MTA-based material and two antibacterial-enhanced MTAs as pulp capping materials in immature permanent dental elements underwent full pulpotomy. The present animal study included 20 Wistar albino rats that, after full pulpotomy, were randomly divided into 4 groups receiving different MTA formulations as pulp capping materials: conventional MTA, Tricalcium aluminate (TCA)- free MTA, and MTA enhanced with metronidazole or doxycycline. Histopathological assessments were carried out at 7- and 28-days post-treatment to evaluate dentinal bridge formation, inflammatory reactions, pulp tissue necrosis and internal resorption. Seven days post-treatment, all groups exhibited inflammation and pulp necrosis, that were minimal in Groups III and IV than Group I. Group II showed a statistically significant difference only in terms of pulp necrosis (p<0.001). At 28-days all Groups showed slight inflammation and pulp necrosis, mainly in Groups I. Dentinal bridge formation was appreciated in all samples belonging to Groups II, III and IV and in 7/10 specimens of Group I, resulting in a statistically significant difference (p≤0.001). TCA-free MTA and antibiotic-enhanced MTAs showed superior performances in dentinal bridge formation and exhibited minimal pulpal necrosis than conventional MTA. The inclusion of antibiotics might contribute to create a more sterile environment that would improve the outcomes, favoring deposition of a mineralized matrix. However, further studies are needed to support these preliminary results. (EEJ-2024-10-157).

Anti-proliferative 2,3-dihydro-1,3,4-thiadiazoles targeting VEGFR-2: Design, synthesis, in vitro, and in silico studies

In this study, we present the design, synthesis, and evaluation of six new thiadiazole derivatives designed as VEGFR-2 inhibitors. The most promising compound, 18b, demonstrated promising inhibitory activity against VEGFR-2, with an IC50 value of 0.165 µg/mL. The in vitro assessments on MCF-7 and HepG2 cell lines revealed the superior anti-proliferative effects of compound 18b, exhibiting IC50 values of 0.06 and 0.17 µM, respectively. Further investigations into the cell cycle distribution of compound 18b on MCF-7 cells exhibited a cell cycle arrest at the S phase (52.96 %) and significantly reducing the percentage of cells in the G0-G1 and G2/M phases. Additionally, compound 18b demonstrated a remarkable pro-apoptotic effect, with 45.29 % total apoptosis, characterized by both early and late apoptosis, and minimal necrosis. These findings were corroborated by RT-PCR analysis, revealing a significant downregulation of the anti-apoptotic gene Bcl2 and upregulation of the pro-apoptotic gene BAX in compound 18b-treated cells compared to control MCF-7 cells. Moreover, in silico studies involving molecular docking, Density Functional Theory (DFT) calculations, Molecular Dynamics (MD) simulations, MM-GBSA, Principle Component Analysis of Trajectories (PCAT), in addition to Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictions underscored the molecular interactions, energetics, and pharmacokinetic properties of compound 18b and the other derivatives further supporting its potential. Our integrated approach, combining in vitro experimens with in silico predictions provides valuable insights into the therapeutic potential of compound 18b as a robust VEGFR-2 inhibitor and lays the groundwork for future optimization.

Experimental Study of Hypolipidemic Effect of Manjal Noiku Kudineer

Hyperlipidemia, is a major stake for the development of serious diseases like atherosclerosis, Coronary Artery Diseases, Stroke. Siddha system of Medicine with the numerous combination of medicines has Manjal Noiku Kudineer(MNK), a Siddha poly herbal formulation indicated for Manjal Noi. This study deals with the Hypolipidemic activity of Manjal Noiku Kudineer on atherogenic diet induced hyperlipidemia in experimental Wistar Albino Rats Place of Study: The study was conducted at Arulmigu Kalasalingam College of Pharmacy, Virudhunagar. Methodology: The study protocol for MNK was reviewed and approved by Institutional Animal Ethics Committee (IAEC), Arulmigu Kalasalingam College of Pharmacy, Virudhunagar, with the IAEC number AKCP/IAEC/10/24-25. The experimental hyperlipidemic diet consists of well-pulverized 400 mg/kg cholesterol, 50 mg/kg cholic acid, and coconut oil. All groups other than the control group were fed the prepared atherogenic meal in lieu of the regular pellet diet. Group I served as normal control, Group II represented hyperlipidemic control rats given an atherogenic diet, Group III and IV represented test groups given MNK 200 mg/kg and MNK 400 mg/kg, respectively, and Group V represented standard-administered atorvastatin (10 mg/kg/day). All groups were compared, observations were noted and the observations were statistically evaluated. Results: The study shows the results of reduction in body weight, blood lipid profile, liver lipid profile of hyperlipidemic rats on treating with the study medicine, which possess hypolipidemic activity. Histopathologic images of rat liver also shown normal parenchyma and parenchyma with minimal necrosis and minimal inflammatory changes on treating with the study medicine MNK. Conclusion: The results stands as a support for MNK hypolipidemic activity, which in turn can be used as a antihyperlipidemic therapeutic agent from the Siddha System of Medicine.

Evaluation of Ablation Parameters to Predict Irreversible Lesion Size During Pulsed Field Ablation.

During pulsed field ablation (PFA), relationships between ablation parameters (contact force [CF], number of burst pulses, impedance decrease, and electrode temperature) and lesion size in beating hearts have not been well validated. A 7.5F-catheter with a 3.5-mm ablation electrode and CF sensor (ThermoCool SmartTouch SF-Dual-Energy, Biosense Webster, Inc, Irwindale, CA) was connected to a PFA system (TRUPULSE2, Biosense Webster, Inc). In 11 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and the skin patch at 219 sites in left ventricle and right ventricle using 12, 18, and 24 burst pulses with 4 different levels of CF: (1) low (n=57; CF, 4-15g; median, 10g); (2) moderate (n=60; CF, 16-30g; median, 22.5g); (3) high (n=68; CF, 32-65g; median, 40g); and (4) no electrode contact (n=34), 2 mm away from the endocardium. Swine were euthanized 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. All PFA lesions with electrode-myocardium contact were well demarcated with triphenyl tetrazolium chloride staining, demonstrating (1) pale central zone (contraction band necrosis with minimal coagulation necrosis), (2) dark brown zone (contraction band necrosis with hemorrhage), and (3) hyperstained red zone by triphenyl tetrazolium chloride (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). Lesion depth increased significantly with increasing CF and the number of PFA burst pulses. An exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlated lesion depth with high accuracy: R=0.809, P<0.0001, ±1.0-mm accuracy in 128 of 163 (79%) lesions, and ±1.5-mm accuracy in 153 of 163 (94%) lesions. Impedance decrease and electrode temperature were poor predictors of lesion size. There were no detectable lesions resulting from ablation without electrode contact. Acute PFA ventricular lesions demonstrate irreversible and reversible lesion boundaries. Electrode-tissue contact is required for effective lesion formation. Lesion depth increases significantly with increasing CF and PFA burst pulses. A new exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlates lesion depth with high accuracy.

Magnetic Resonance Imaging Features of Sporadic Optic Chiasmatic-Hypothalamic Gliomas and Correlation with Histopathology and BRAF Gene Alterations.

Sporadic optic chiasmatic-hypothalamic gliomas (OCHGs), though histologically low-grade tumors, manifest as aggressive neoplasms radiologically, leading to difficulty in diagnosis. Molecular alterations of the BRAF gene are detectable in a majority of sporadic OCHGs. The purpose of our study was to elucidate the characteristic imaging features of sporadic OCHGs and to investigate whether imaging phenotypes could potentially correlate with specific BRAF gene alterations associated with these tumors. We retrospectively reviewed baseline magnetic resonance (MR) images and medical records of 26 patients with histopathologically proven sporadic OCHGs. MR imaging (MRI) features were systematically evaluated. Statistical analysis was performed to determine whether there was a significant association between imaging findings and BRAF molecular alterations. Twenty-two cases (84.6%) presented with solid-cystic masses, while four (15.4%) presented with purely solid lesions. In all 26 cases, the solid component revealed central necrosis; there was minimal necrosis in 11 cases (42.3%), moderate in 8 (30.7%), and marked in 7 (26.9%). The presence of multiple cysts (>4) and minimal necrosis showed a significant association with BRAFV600E mutation (P < 0.005). Marked necrosis in the solid component significantly correlated with BRAF wild genotype (P < 0.001). The presence of a single peripheral cyst significantly correlated with BRAF fusion (P = 0.04). Sporadic OCHGs have a distinctive appearance on imaging. The solid-cystic composition coupled with varying degrees of central necrosis are clues to the radiological diagnosis of this entity and can facilitate early recognition in clinical practice. Imaging could potentially serve as a non-invasive predictor of the BRAF alteration status, thereby serving as a prognostic marker and guiding personalized management.

High Intensity Focused Ultrasound (20MHz) and Cryotherapy as Therapeutic Options for Granuloma Annulare and Other Inflammatory Skin Conditions.

In dermatology, inflammatory skin conditions impose a substantial burden worldwide, with existing therapies showing limited efficacy and side effects. This report aims to compare a novel immunological activation induced by hyperthermic 20MHz high intensity focused ultrasound (HIFU) with conventional cryotherapy. The bioeffects from the two methods are initially investigated by numerical models, and subsequently compared to clinical observations after treatment of a patient with the inflammatory disease granuloma annulare (GA). Clinical responses to moderate energy HIFU and cryotherapy were analysed using numerical models. HIFU-induced pressure and heat transfer were calculated, and a three-layer finite element model simulated temperature distribution and necrotic volume in the skin. Model output was compared to 22 lesions treated with HIFU and 10 with cryotherapy in a patient with GA. Cryotherapy produced a necrotic volume of 138.5mm3 at - 92.7°C. HIFU at 0.3-0.6J/exposure and focal depths of 0.8 or 1.3mm generated necrotic volumes up to only 15.99mm3 at temperatures of 68.3-81.2°C. HIFU achieved full or partial resolution in all treated areas, confirming its hyperthermic immunological activation effect, while cryotherapy also resolved lesions but led to scarring and dyspigmentation. Hyperthermic immunological activation of 20MHz HIFU shows promise for treating inflammatory skin conditions as exemplified by GA. Numerical models demonstrate minimal skin necrosis compared to cryotherapy. Suggested optimal HIFU parameters are 1.3mm focal depth, 0.4-0.5J/exposure, 1mm spacing, and 1mm margin. Further studies on GA and other inflammatory diseases are recommended.

Comparative outcome of single versus two double-pigtail stents for endoscopic drainage of pancreatic fluid collections with minimal necrosis: a retrospective analysis.

Endoscopic ultrasound (EUS)-guided cystogastrostomy is the treatment of choice for managing symptomatic pancreatic fluid collections (PFC). However, studies on the number of stents for optimal drainage of PFCs are limited. Hence, the present study was conducted to compare the outcome of single versus two double-pigtail stents for endoscopic drainage of PFCs. This is a single-center, retrospective analysis of patients undergoing endoscopic drainage of PFCs with minimal necrosis (pseudocyst or walled-off necrosis with <30% solid content) at a tertiary center in South India from October 2020 to October 2022. Post-procedure, patients were followed up for clinical improvement, and stents were removed after documentation of cyst size reduction on imaging. Sixty-three patients (82.5% males, median age: 34 years) fulfilling the selection criteria were included. For single stent placement (n = 47), stents of size 8.5 Fr or 10 Fr were used, while for placement of two stents (n = 16), 7 Fr stents were used. The technical success rate was 100%. Intraprocedural and early postprocedural adverse events (all mild to moderate) were comparable between the groups (17.0% with single stent vs. 25.0% with two stents, p = NS). Clinical success was achieved in 93.6% of patients, with no difference between both groups. Three patients in the single stent group required additional procedures. All patients underwent successful stent removal after a median follow-up of 14 weeks. A single pigtail stent of 8.5 Fr or 10 Fr size for EUSguided cystogastrostomy provides efficacy and safety similar to that of two stents.

Semisynthesis of 5-O-ester derivatives of renieramycin T and their cytotoxicity against non-small-cell lung cancer cell lines

The semisynthesis of 5-O-ester derivatives of renieramycin T was accomplished through the photoredox reaction of renieramycin M (1), a bistetrahydroisoquinolinequinone alkaloid isolated from the Thai blue sponge Xestospongia sp. This process led to the conversion of compound 1 to renieramycin T (2), which was subsequently subjected to Steglich esterification with appropriate acylating agents containing linear alkyl, N-tert-butoxycarbonyl-L-amino, and heterocyclic aromatic substituent. Notably, the one-pot transformation, combining the photoredox reaction and esterification led to the formation of 7-O-ester derivatives of renieramycin S due to hydrolysis. Subsequently, the in vitro cytotoxicity of the 17 semisynthesized derivatives against human non-small-cell lung cancer (NSCLC) cells in parallel with normal cell lines was evaluated. Among the tested compounds, 5-O-(3-propanoyl) ester of renieramycin T (3b) exhibited potent cytotoxic activity with half-maximal inhibitory concentration (IC50) values at 33.44 and 33.88 nM against H292 and H460 cell lines, respectively. These values were within the same range as compound 1 (IC50 = 34.43 and 35.63 nM) and displayed twofold higher cytotoxicity compared to compound 2 (IC50 = 72.85 and 83.95 nM). The steric characteristics and aromatic orientation of the 5-O-ester substituents played significant roles in their cytotoxicity. Notably, derivative 3b induced apoptosis with minimal necrosis, in contrast to the parental compound 1. Hence, the relationship between the structure and cytotoxicity of renieramycin–ecteinascidin hybrid alkaloids was investigated. This study emphasizes the potential of the series of 5-O-ester derivatives of renieramycin T as promising leads for the further development of potential anti-NSCLC agents.

Free Thoracodorsal Artery Perforator Flap for Head and Neck Reconstruction: An Indian Experience.

Background We describe our experience with use of free thoracodorsal artery perforator (TDAP) flap for head and neck (H&N) cancer reconstruction, with respect to the patient and disease profile, suitable defect characteristics, the reconstructive technique, and complications. Methods Consecutive patients ( N = 26) undergoing free TDAP flap for H&N onco-reconstruction, in a single center, were included from January 2015 to December 2018 and the data were analyzed. Results Perforator(s) were reliably predicted preoperatively, using handheld Doppler. Lateral position was comfortable for the harvest. Twenty flaps were harvested on a single perforator, more commonly musculocutaneous ( n = 16). The thoracodorsal nerve and latissimus dorsi muscle could be preserved, completely in almost all cases. The skin paddle was horizontally ( n = 5) or vertically ( n = 21) oriented, both giving a satisfactory scar. The flap was used as a single island or two islands by de-epithelializing intervening skin. Pedicle length was sufficient in all cases. Four cases were explored for suspected venous insufficiency. Two had thrombosis, of which one was salvaged, while the other necrosed. One flap had minimal partial necrosis, which was managed with secondary suturing. The 5-year follow-up showed good oral competence, mouth opening, and cosmetic satisfaction among patients. Conclusion TDAP flap provides all the advantages of a perforator-based free flap and of back as a donor site with close color match to the face, relatively hairless, and thickness in between the thigh and the forearm. It can be a useful tool to provide an ideal functional and aesthetic outcome, with a hidden donor site and minimal donor site morbidity in selected cases.

Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): One-Year Safety and Efficacy Outcomes from a Multicenter Phase I Trial

The combination of immunotherapy and single-fraction stereotactic radiosurgery (SRS) for treatment of metastatic brain disease has yielded symptomatic radiation necrosis rates as high as 20% (PMID: 29327059). Consequently, the Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) multicenter phase I trial (registered at clinicaltrials.gov, NCT04047602) was created to address whether reduced-dose SRS can improve morbidity without compromising efficacy. In this report we present our one-year findings. Eligibility for RADREMI enrollment required brain metastases patients with: a) Histologically-confirmed primary malignancy, b) Receipt of immunotherapy within 30 days of SRS, c) 1-10 MRI-visible brain metastases, d) Estimated median survival of at least 6 months (via disease-specific graded prognostic assessment), and e) No history of whole brain radiation therapy. Reduced-dose SRS utilized 18 Gy for lesions 0-2 cm, 14 Gy for lesions 2.1-3 cm, and 12 Gy for lesions 3.1-4 cm. Symptomatic radiation necrosis was defined as imaging findings consistent with radiation necrosis combined with clinical symptoms requiring steroid administration and/or operative intervention. Local control was defined by Response Assessment in Neuro-Oncology (RANO) criteria. From December 18, 2019 to June 30, 2022, 54 lesions in 17 patients were treated on RADREMI with at least one-year of follow-up. One-year local control occurred in 52 of 54 lesions and in 15 of 17 patients, yielding control rates of 96% per lesion and 88% per patient. Radiographic radiation necrosis occurred in 2 of 54 lesions (4%). No symptomatic radiation necrosis occurred. Our findings of concurrent immunotherapy + reduced-dose SRS at one-year post-treatment revealed excellent local control (96%) with no symptomatic radiation necrosis, and minimal radiographic radiation necrosis. These results attest to the durability of the safety and efficacy of reduced-dose SRS with immunotherapy for metastatic brain disease.

A Weakly Supervised Deep Learning Framework for Whole Slide Classification to Facilitate Digital Pathology in Animal Study.

The pathology of animal studies is crucial for toxicity evaluations and regulatory assessments, but the manual examination of slides by pathologists remains time-consuming and requires extensive training. One inherent challenge in this process is the interobserver variability, which can compromise the consistency and accuracy of a study. Artificial intelligence (AI) has demonstrated its ability to automate similar examinations in clinical applications with enhanced efficiency, consistency, and accuracy. However, training AI models typically relies on costly pixel-level annotation of injured regions and is often not available for animal pathology. To address this, we developed the PathologAI system, a "weakly" supervised approach for WSI classification in rat images without explicit lesion annotation at the pixel level. Using rat liver imaging data from the Open TG-GATEs system, PathologAI was applied to predict necrosis of n = 816 WSIs (377 controls). TG-GATEs studied 170 compounds at three dose levels (low, middle, and high) for four time points (3, 7, 14, and 28 days). PathologAI first preprocessed WSIs at the tile level to generate a high-level representation with a Generative Adversarial Network architecture. The prediction of liver necrosis relied on an ensemble model of 5 CNN classifiers trained on 335 WSIs. The ensemble model achieved notable classification accuracy on the holdout test set: 87% among 87 control slides free of findings, 83% among 120 controls with spontaneous necrosis, 67% among 147 treated animals with spontaneous minimal or slight necrosis, and 59% among 127 treated animals with minimal or slight necrosis caused by the treatment. Importantly, PathologAI was able to discriminate WSIs with spontaneous necrosis from those with treatment related necrosis and discriminated mild lesion level findings (slight vs minimal) and between treatment dose levels. PathologAI could provide an inexpensive and rapid screening tool to assist the digital pathology analysis in preclinical applications and general toxicological studies.

Anticancer effects of herbal medicine Emelia-M, Mshikazi and Delosma H against human leukaemia cells.

Leukaemia is one of the three major types of blood cancers that lead to the overproduction of abnormal white blood cells. Emelia M (EMB), Mshikazi and Delosma H are herbal medicines that are being used by traditional healers in KwaZulu-Natal, South Africa to treat leukaemia and other diseases. To gain insight into the safety (non-toxic effect), anti-cancer activity, mechanisms of action and phytochemical profiles of traditional herbal medicines (Emelia M (EMB), Mshikazi and Delosma H) in South Africa. The viability of human peripheral blood mononuclear cells (PBMCs), monocytic (THP-1) and T-lymphocyte (Jurkat) cell lines exposed to varying concentrations of aqueous extracts of the three herbal medicines were assessed using adenosine triphosphate (ATP) assay. All three extracts showed a dose-dependent effect on the viability of PBMCs. Cell viability decreased with increasing concentrations of extracts when compared with the untreated cells at 24 and 48 hours. The inhibitory activities (IC50) of the extract were found in the order of Mshikazi > EMB, > Delosma H. All the extracts induced apoptosis with minimal necrosis. Many bioactive compounds that have been previously reported to have anticancer effects were identified in the extracts. Mshikazi extract significantly inhibited the growth of THP-1 and Jurkat cells and induced cell death through apoptosis than the other two extracts.

Papillary Endothelial Hyperplasia

A man in his 30s had a unilateral mass of the epididymis. There was no prior history of local trauma, and ultrasonographic imaging did not reveal the presence of any other testicular abnormality. A 1.4-cm unilocular cystic lesion was excised. Histopathologic examination showed the presence of blood vessels with organizing thrombi adjacent to the epididymis (Figure 1A, B ). On microscopic examination, several foci of proliferative clusters of cells with epithelioid to vaguely spindled morphology were identified (Figure 1C, D). What is the lineage of the epithelioid cells, and is this lesion benign or malignant?a.Vascular lineage, malignant (angiosarcoma)b.Carcinoma, malignantc.Vascular lineage, benign (papillary endothelial hyperplasia)d.Melanoma, malignant Answer: c. Vascular lineage, benign (papillary endothelial hyperplasia) The images show the presence of an intravascular lesion with organizing thrombus that is broken down into collagenized clumps admixed with hemorrhagic material (Figure 2A, B ). These collagenized clusters are lined by vascular endothelial cells, and immunohistochemistry for ERG and CD31 confirms vascular lineage (Figure 2C, D). These findings are consistent with papillary endothelial hyperplasia.1Akdur N.C. Donmez M. Gozel S. Ustun H. Hucumenoglu S. Intravascular papillary endothelial hyperplasia: histomorphological and immunohistochemical features.Diagn Pathol. 2013; 8: 167Crossref PubMed Scopus (51) Google Scholar Papillary endothelial hyperplasia is thought to represent breakdown of intravascular thrombi with accompanying ingrowth of vascular endothelial cells along the edges of thrombotic material. In late stages, as in this case, these lesions may impart an appearance of a papillary lesion with an anastomotic network of vascular endothelial cells that is frequently misinterpreted as an angiosarcoma. However, in contrast to angiosarcoma, these lesions are almost always exclusively intravascular and lack infiltrative growth. Infrequently, papillary endothelial hyperplasia may be recognized in an extravascular location secondary to rupture or as part of organization of an extravascular hematoma. These lesions exhibit minimal nuclear pleomorphism, mitotic activity, or necrosis. Finally, papillary endothelial hyperplasia has an excellent prognosis and does not recur when completely excised.

Bladder Postoperative Spindle Cell Nodule: Malignant Mimicry in the Postoperative Setting

Bladder Postoperative Spindle Cell Nodule: Malignant Mimicry in the Postoperative Setting

18 F FDG PET-CT Scan Findings in a Rare Case of Pulmonary Hyalinising Granuloma

Pulmonary hyalinising granuloma (PHG) is a benign lung disease. It is a rare disease of unknown aetiology. Less than 150 cases are reported. Its aetiology has not been established but the underlying cause is thought to be the deposition of an immune complex in lung parenchyma or autoimmune process. It usually presents as solitary or multiple lung nodules. PHG has a good prognosis. Solitary lesions are treated by resection and multiple lesions are treated with immunosuppressive drugs with variable responses. Here, we report a case of a 68-year-old female who presented with two episodes of haemoptysis. On investigation, chest computed tomography (CT) reveals multiple lung nodules on both sides, 18 F fluorodeoxyglucose (FDG) positron emission tomography and CT scan reveal mildly FDG avid and non-FDG avid subpleural and parenchymal nodular lesions of varying sizes with calcification noted scattered diffusely in both lung fields. Pathology findings are suggestive of fibrocollagenous tissue with tiny foci of epithelial cells arranged as papillae, cuboid cells with minimal atypia, mitosis, and necrosis not seen and no lymphoid tissue seen, suggestive of PHG.

Engineering second-generation TCR-T cells by site-specific integration of TRAF-binding motifs into the CD247 locus

BackgroundThe incorporation of co-stimulatory signaling domains into second-generation chimeric antigen receptors (CARs) significantly enhances the proliferation and persistence of CAR-T cells in vivo, leading to successful clinical outcomes.MethodsTo achieve such...

Rheumatoid nodules: a narrative review of histopathological progression and diagnostic consideration.

Rheumatoid nodules (RNs) are the most common extra-articular manifestation of rheumatoid arthritis and are also seen in patients with other autoimmune and inflammatory diseases. The development of RNs includes histopathological stages of acute unspecified inflammation, granulomatous inflammation with no or minimal necrosis, necrobiotic granulomas typically with central fibrinoid necrosis surrounded by palisading epithelioid macrophages and other cells, and likely an advanced stage of "ghost" lesions containing cystic or calcifying/calcified areas. In this article, we review RN pathogenesis, histopathological features in different stages, diagnostically related clinical manifestations, as well as diagnosis and differential diagnosis of RNs with an in-depth discussion about challenges in distinguishing RNs from their mimics. While the pathogenesis of RN formation remains elusive, it is hypothesized that some RNs with dystrophic calcification may be in transition and may be in coexistence or collision with another lesion in patients with RA or other soft tissue diseases and comorbidities. The diagnosis of typical or mature RNs in usual locations can be readily made by clinical findings often with classic RN histopathology, but in many cases, particularly with atypical or immature RNs and/or unusual locations, the clinical and histopathological diagnosis can be challenging requiring extensive examination of the lesional tissue with histological and immunohistochemical markers to identify unusual RNs in the clinical context or other lesions that may be coexisting with classic RNs. Proper diagnosis of RNs is critical for appropriate treatment of patients with RA or other autoimmune and inflammatory diseases.

Selective Androgen Receptor Modulators: An Emerging Liver Toxin.

Selective androgen receptor modulators (SARMs) are a class of nonsteroidal drugs that are favored over anabolic androgenic steroids (AASs) for their tissue-selectivity and improved side-effect profile. These drugs have been evaluated for treatment of various diseases including muscle-wasting disorders, osteoporosis, and breast cancer. Despite lacking approval for therapeutic use, SARMs are widely used recreationally as performance enhancing drugs by bodybuilders and athletes. In recent years, cases of drug-induced liver injury (DILI) secondary to SARMs have begun to emerge, but little is known regarding their hepatotoxicity. In this review, we provide current knowledge regarding DILI from SARMs. A literature search was conducted regarding SARMs and liver injury to evaluate relevant cases and information. SARMs have been associated with a cholestatic syndrome congruent with that of DILI from AASs, and it consists of a bland cholestasis in which there is minimal bile duct injury, inflammation, or necrosis. Patients present with an insidious onset of jaundice with marked hyperbilirubinemia and mild hepatic enzyme elevations. No clear treatment exists, although patients typically show improvement with cessation of the offending SARM. Given the novelty of these drugs, further study is necessary to understand diagnosis, management, and complications of SARM-related DILI.

Postmastectomy Immediate Implant-Based Breast Reconstruction with Scarless Latissimus Dorsi Flap-a Simple and Versatile Technique.

In low- and middle-income countries, breast reconstruction is not widely practiced due to a lack of specialized equipment, skilled personnel, and high costs. The scarless latissimus dorsi flap is a useful technique which can harvest a major portion of the latissimus dorsi muscle using the same mastectomy incision without requiring repositioning of the patient, to cover the lower pole of prosthesis for reconstruction. The aim of this study was to assess and evaluate the cosmetic results and complications of scarless LD flap used as a lower pole cover in post-mastectomy breast reconstruction with implants. This is a pilot study of 18 breast cancer patients who underwent implant-based scarless LD flap breast reconstructions during a period of 4years from 2017 to 2021. A questionnaire based on relevant subscales of BREAST-Q scores was completed by all the patients and used for evaluation. A total of 18 patients who underwent 20 surgeries were evaluated for the study. The median age was 44.5years. The mean operative time was observed to be 164.50min. The mean length of hospital stay was 3.1days. From the Breast Q subscales, the mean cosmetic score was 31 out of 36 (range 27-36) (higher score reflecting better cosmetic outcome), and the mean physical well-being score was 17.25 out of 54 (range 12-29) (lower score reflecting better outcome). Overall complications were observed to be 20% which included minimal flap necrosis in 2 patients which was managed conservatively, and seromas in 2 patients which needed ultrasound-guided aspirations twice. There were no major complications. The scarless LD flap provides an adequate lower pole muscle coverage for implants in breast reconstruction. It has less morbidity and good cosmetic outcomes. It is time and cost-effective, requires no patient repositioning, and uses standard breast instruments.

Outcome of Limberg Flap Reconstruction in the Management of Pilonidal Sinus Disease: A Retrospective Study

Introduction: Pilonidal Sinus Disease (PSD) is a tract or cavity commonly seen in the sacrococcygeal region, usually containing a tuft of hair. It is mostly observed in drivers who have excessive hair in the natal cleft region. Although several surgical procedures have been described for the management of PSD, none have been universally accepted as the gold standard. Limberg flap reconstruction, following wide excision, offers a tension-free repair using a well-vascularised flap. This technique flattens the natal cleft, avoiding a midline scar and reducing the chance of recurrence. Aim: The aim of this study was to determine the outcomes of Limberg flap reconstruction in sacrococcygeal PSD. Materials and Methods: A retrospective descriptive study was conducted in the Department of General Surgery at M S Ramaiah Medical College, Bangalore, Karnataka, India. The study duration was six years, from January 2011 to January 2017. The study included a total of 40 patients aged between 15-70 years, with Tezel type III sacrococcygeal Pilonidal Disease (PND), who underwent the Limberg flap procedure. Data was collected and analysed from January to June 2021. Outcome measures such as duration of hospital stay, time required to return to work, and procedure-related complications associated with procedure were analysed and entered into an Excel sheet. Results: The mean age of the study participants was 18.02±6.87 years. Out of the 40 patients, 4 (10%) developed complications. Superficial wound infection was observed in 1 (2.5%) patient, which healed within two weeks. Minimal flap necrosis was observed in 2 (5%) patients, who underwent debridement and dressings on an outpatient basis. The wounds healed within three to four weeks. Recurrence was reported in 1 (2.5%) patient. The mean time to return to work was 18.7±4.88 days. Conclusion: Limberg flap reconstruction for sacrococcygeal PSD is a simple technique with a lower complication rate, faster return to normal activity, and a low recurrence rate.