Management of non-functioning kidney due to pelvi-ureteric junction obstruction in pediatric age group: an observational study.

INTRODUCTION: A non-functional kidney (NFK) has been defined as one having paper-thin parenchyma, and split renal function (SRF) of < 10% on a nuclear scan. There are differences of opinion about nephrectomy or pyeloplasty in these patients. The present study was conducted to assess our management strategy of renal salvage for NFK. MATERIALS AND METHODS: It was a retrospective cohort study from January 2015 to July 2022, patients having SRF < 10% were included. These patients underwent ultrasound-guided percutaneous nephrostomy (PCN). A repeat nuclear scan was performed after 3 months. If SRF increased to > 10%, pyeloplasty was performed. RESULTS: Fifteen patients were managed. The mean age was 24.67 ± 23.61 months. Male to female ratio was 4:1. The initial mean SRF was 6.67 ± 2.85, which improved to 16.80 ± 4.69 after 3 months of placing the PCN (p < 0.001). The corresponding changes in the mean effective renal plasma flow (ERPF) were 60.13 ± 24.08 to 106.53 ± 24.61 (p < 0.001). There was no complaint after the placement of PCN. All patients underwent dismembered pyeloplasty. CONCLUSION: In NFK due to PUJO, expectant treatment in form of PCN followed by pyeloplasty appears to be the primary treatment modality, and nephrectomy may not be needed in any of them.

Surface Acoustic Wave Propagation of GaN/Sapphire Integrated with a Gold Guiding Layer.

Gallium nitride (GaN), widely known as a wide bandgap semiconductor material, has been mostly employed in high power devices, light emitting diodes (LED), and optoelectronic applications. However, it could be exploited differently due to its piezoelectric properties, such as its higher SAW velocity and strong electromechanical coupling. In this study, we investigated the affect of the presence of a guiding layer made from titanium/gold on the surface acoustic wave propagation of the GaN/sapphire substrate. By fixing the minimum thickness of the guiding layer at 200 nm, we could observe a slight frequency shift compared to the sample without a guiding layer, with the presence of different types of surface mode waves (Rayleigh and Sezawa). This thin guiding layer could be efficient in transforming the propagation modes, acting as a sensing layer for the binding of biomolecules to the gold layer, and influencing the output signal in terms of frequency or velocity. The proposed GaN/sapphire device integrated with a guiding layer could possibly be used as a biosensor and in wireless telecommunication applications.

Study the Possibility of Creating Mucosal Valve Mechanism at Ureteric Orifice without Obstructing the Urine Outflow but Preventing the Urine Backflow into the Ureters.

Objective: To study the possibility of creating mucosal valve mechanism at ureteric orifice without obstructing the urine outflow but preventing the urine backflow into the ureters. Materials and Methods: Ethical waiver was obtained from the institutional ethical committee. Prospective experimental study was conducted on the post-mortem specimen of intact bladder with urethra and bilateral ureters retrieved from the already slaughtered lamb available in the meat market. Feeding tube inserted via urethral opening into the bladder lumen and bladder inflated with saline demonstrated no reflux of urine via transverse cut opening of ureters. Bladder lumen opened, ureteric orifices incised backwards to eliminate the obliquity. After closing the bladder opening, saline inflation test demonstrated bilateral reflux of saline via cut openings of bilateral ureters. Bladder was re-opened. The upper limb of horizontal U started 10 mm lateral and 8 mm above the refluxing ureteric orifice. Distal most curvature of horizontal U was kept 5 mm medial to ureteric orifice continuing along the lower limb of horizontal U terminating 10 mm lateral and 8 mm below the refluxing ureteric orifice, mucosal flaps from superior and inferior incision mobilized and edges joined to cover the ureteric orifice creating a flap valve mechanism. Influx of saline via cut end of ureters demonstrated no obstruction. Bladder was closed. Saline inflation test and contrast study demonstrated abolition of reflux on flap side and persistence of reflux on another side. Results: Five such experiments were conducted. On the side where the valve was created, Vesicoureteral reflux was abolished in four but in one minimal reflux still persisted. Conclusion: Creating a mucosal flap valve around the ureteric orifice can prevent reflux in 80% of cases without obstruction and without the necessity of ureteric mobilization or creating submucosal tunnel.

The wandering ventriculoperitoneal shunt and the scope of its salvage.

PURPOSE: Distal shunt tube migration following ventriculoperitoneal (VP) shunt placement in children is mostly managed by an initial shunt diversion/removal and subsequent replacement. Lately, shunt salvage is being used as an alternative in certain conditions. We have focused on the situations where one can consider or disregard shunt salvage in such cases. METHOD: A retrospective study of children treated for distal shunt migration following VP shunt placement between January 2013 and December 2019. RESULT: Seventeen children were managed for over 7 years. These included cutaneous extrusions (n = 4), hollow viscus perforation (n = 6), inguinal hernias (n = 5), and umbilical extrusion (n = 2). The surgical treatment varied from a cutaneous wound closure (with a tube in situ), temporary external shunt diversion, and laparotomy with shunt reposition into the peritoneal cavity. Shunt salvage was possible in three cases, whereas in 2 cases even though shunt salvage was possible, it was not feasible due to a short residual shunt length. CONCLUSION: VP shunt salvage is possible in certain cases of distal shunt migration with a functional uninfected shunt. Small cutaneous extrusions can be covered by a local skin flap. Also, one should consider the residual intraperitoneal shunt length before its salvage in small children.

Angiotensin-converting Enzyme Inhibitors: Can it be a Potential Treatment of Infantile Hemangioma.

AIMS: The aim of the sudy was to evaluate potential role of oral captopril, an angiotensin-converting enzyme (ACE) inhibitor, and in treatment of infantile hemagioma (IH) and report our preliminary results. METHODS: This prospective study included 18 children with IH admitted in the department of pediatric surgery with no history of prior treatment of any type. Baseline blood pressure (BP), electrocardiogram, two-dimensional echocardiography, serum electrolytes, and renal function test (RFT) were noted. Oral captopril was started as first-line drug at a dose of 0.1 mg/kg orally 12 h with gradually increase of dosage up to 2.0 mg/kg 12 h over the period of 10 days with monitoring of BP, serum electrolytes, RFT, and occurrence of any side effect. If no side effects were noted and patients were stable, they were discharged and followed up until 6 months after stopping treatment. During follow-up, response to treatment was documented clinically and photographically. Development of any side effect was also noted. RESULTS: Excellent response to captopril was noticed in nine patients over 16-18 months. Four patients showed good response. Oral propranolol had to be administered alternatively in one patient showing fair response during the initial 4 months but no response afterward and in four patients showing no response at all. One patient developed an allergic reaction to propranolol and was started oral corticosteroid. These five patients had near complete resolution of lesion for the next 8-10 months. CONCLUSIONS: ACE inhibitors might have a role, though slow, in the involution of IHs. Therefore, these may have the potential to emerge as an alternative treatment for IH in future after confirmation with randomized studies with propranolol.

Oral Propranolol in the Treatment of Ulcerated Bleeding Scrotal Arteriovenous Malformation.

Arteriovenous malformations (AVMs) of the scrotum are very rare, with only 35 adult cases in the literature. An 8-year-old boy presented with an ulcerated bleeding AVM of the scrotum. The patient was resuscitated and managed conservatively initially. After the control of bleeding, oral propranolol was started. There was a decrease in the size of scrotal and penile swelling, healing of ulcer with total healing by 1 month, and no recurrence of bleeding episode. To the best of our knowledge, this was the first case of pediatric scrotal AVM treated by oral propranolol.

Acetyltransferase p300 inhibitor reverses hypertension-induced cardiac fibrosis.

Epigenetic dysregulation plays a crucial role in cardiovascular diseases. Previously, we reported that acetyltransferase p300 (ATp300) inhibitor L002 prevents hypertension-induced cardiac hypertrophy and fibrosis in a murine model. In this short communication, we show that treatment of hypertensive mice with ATp300-specific small molecule inhibitor L002 or C646 reverses hypertension-induced left ventricular hypertrophy, cardiac fibrosis and diastolic dysfunction, without reducing elevated blood pressures. Biochemically, treatment with L002 and C646 also reverse hypertension-induced histone acetylation and myofibroblast differentiation in murine ventricles. Our results confirm and extend the role of ATp300, a major epigenetic regulator, in the pathobiology of cardiac hypertrophy and fibrosis. Most importantly, we identify the efficacies of ATp300 inhibitors C646 and L002 in reversing hypertension-induced cardiac hypertrophy and fibrosis, and discover new anti-hypertrophic and anti-fibrotic candidates.

Plasminogen Activator Inhibitor-1 Is a Marker and a Mediator of Senescence.

PAI-1 (plasminogen activator inhibitor-1) is a member of the evolutionarily conserved serine protease inhibitor family and a potent and rapid-acting inhibitor of both of the mammalian plasminogen activators. Organismal homeostasis requires physiological levels of endogenous PAI-1, and increased PAI-1 production guides the onset and progression of numerous human diseases and contributes to the multimorbidity of aging. Both chronological and stress-induced accelerated aging are associated with cellular senescence and accompanied by marked increases in PAI-1 expression in tissues. Recent studies suggest that PAI-1 is not only a marker but also a key mediator of cellular senescence and organismal aging. Here, we review the significance of PAI-1 as a bonafide marker, as well as a critical mediator, of cellular senescence associated with aging and aging-related pathologies.

Outcome prediction of intracranial aneurysm treatment by flow diverters using machine learning.

OBJECTIVEFlow diverters (FDs) are designed to occlude intracranial aneurysms (IAs) while preserving flow to essential arteries. Incomplete occlusion exposes patients to risks of thromboembolic complications and rupture. A priori assessment of FD treatment outcome could enable treatment optimization leading to better outcomes. To that end, the authors applied image-based computational analysis to clinically FD-treated aneurysms to extract information regarding morphology, pre- and post-treatment hemodynamics, and FD-device characteristics and then used these parameters to train machine learning algorithms to predict 6-month clinical outcomes after FD treatment.METHODSData were retrospectively collected for 84 FD-treated sidewall aneurysms in 80 patients. Based on 6-month angiographic outcomes, IAs were classified as occluded (n = 63) or residual (incomplete occlusion, n = 21). For each case, the authors modeled FD deployment using a fast virtual stenting algorithm and hemodynamics using image-based computational fluid dynamics. Sixteen morphological, hemodynamic, and FD-based parameters were calculated for each aneurysm. Aneurysms were randomly assigned to a training or testing cohort in approximately a 3:1 ratio. The Student t-test and Mann-Whitney U-test were performed on data from the training cohort to identify significant parameters distinguishing the occluded from residual groups. Predictive models were trained using 4 types of supervised machine learning algorithms: logistic regression (LR), support vector machine (SVM; linear and Gaussian kernels), K-nearest neighbor, and neural network (NN). In the testing cohort, the authors compared outcome prediction by each model trained using all parameters versus only the significant parameters.RESULTSThe training cohort (n = 64) consisted of 48 occluded and 16 residual aneurysms and the testing cohort (n = 20) consisted of 15 occluded and 5 residual aneurysms. Significance tests yielded 2 morphological (ostium ratio and neck ratio) and 3 hemodynamic (pre-treatment inflow rate, post-treatment inflow rate, and post-treatment aneurysm averaged velocity) discriminants between the occluded (good-outcome) and the residual (bad-outcome) group. In both training and testing, all the models trained using all 16 parameters performed better than all the models trained using only the 5 significant parameters. Among the all-parameter models, NN (AUC = 0.967) performed the best during training, followed by LR and linear SVM (AUC = 0.941 and 0.914, respectively). During testing, NN and Gaussian-SVM models had the highest accuracy (90%) in predicting occlusion outcome.CONCLUSIONSNN and Gaussian-SVM models incorporating all 16 morphological, hemodynamic, and FD-related parameters predicted 6-month occlusion outcome of FD treatment with 90% accuracy. More robust models using the computational workflow and machine learning could be trained on larger patient databases toward clinical use in patient-specific treatment planning and optimization.

Epigenetics in Reactive and Reparative Cardiac Fibrogenesis: The Promise of Epigenetic Therapy.

Epigenetic changes play a pivotal role in the development of a wide spectrum of human diseases including cardiovascular diseases, cancer, diabetes, and intellectual disabilities. Cardiac fibrogenesis is a common pathophysiological process seen during chronic and stress-induced accelerated cardiac aging. While adequate production of extracellular matrix (ECM) proteins is necessary for post-injury wound healing, excessive synthesis and accumulation of extracellular matrix protein in the stressed or injured hearts causes decreased or loss of lusitropy that leads to cardiac failure. This self-perpetuating deposition of collagen and other matrix proteins eventually alter cellular homeostasis; impair tissue elasticity and leads to multi-organ failure, as seen during pathogenesis of cardiovascular diseases, chronic kidney diseases, cirrhosis, idiopathic pulmonary fibrosis, and scleroderma. In the last 25 years, multiple studies have investigated the molecular basis of organ fibrosis and highlighted its multi-factorial genetic, epigenetic, and environmental regulation. In this minireview, we focus on five major epigenetic regulators and discuss their central role in cardiac fibrogenesis. Additionally, we compare and contrast the epigenetic regulation of hypertension-induced reactive fibrogenesis and myocardial infarction-induced reparative or replacement cardiac fibrogenesis. As microRNAs-one of the major epigenetic regulators-circulate in plasma, we also advocate their potential diagnostic role in cardiac fibrosis. Lastly, we discuss the evolution of novel epigenetic-regulating drugs and predict their clinical role in the suppression of pathological cardiac remodeling, cardiac aging, and heart failure. J. Cell. Physiol. 232: 1941-1956, 2017. © 2016 Wiley Periodicals, Inc.

MiR-125b Is Critical for Fibroblast-to-Myofibroblast Transition and Cardiac Fibrosis.

BACKGROUND: Cardiac fibrosis is the pathological consequence of stress-induced fibroblast proliferation and fibroblast-to-myofibroblast transition. MicroRNAs have been shown to play a central role in the pathogenesis of cardiac fibrosis. We identified a novel miRNA-driven mechanism that promotes cardiac fibrosis via regulation of multiple fibrogenic pathways. METHODS AND RESULTS: Using a combination of in vitro and in vivo studies, we identified that miR-125b is a novel regulator of cardiac fibrosis, proliferation, and activation of cardiac fibroblasts. We demonstrate that miR-125b is induced in both fibrotic human heart and murine models of cardiac fibrosis. In addition, our results indicate that miR-125b is necessary and sufficient for the induction of fibroblast-to-myofibroblast transition by functionally targeting apelin, a critical repressor of fibrogenesis. Furthermore, we observed that miR-125b inhibits p53 to induce fibroblast proliferation. Most importantly, in vivo silencing of miR-125b by systemic delivery of locked nucleic acid rescued angiotensin II-induced perivascular and interstitial fibrosis. Finally, the RNA-sequencing analysis established that miR-125b altered the gene expression profiles of the key fibrosis-related genes and is a core component of fibrogenesis in the heart. CONCLUSIONS: In conclusion, miR-125b is critical for induction of cardiac fibrosis and acts as a potent repressor of multiple anti-fibrotic mechanisms. Inhibition of miR-125b may represent a novel therapeutic approach for the treatment of human cardiac fibrosis and other fibrotic diseases.

Methanol oxidation on stoichiometric and oxygen-rich RuO2(110).

We used temperature-programmed reaction spectroscopy (TPRS) to investigate the adsorption and oxidation of methanol on stoichiometric and O-rich RuO2(110) surfaces. We find that the complete oxidation of CH3OH is strongly preferred on stoichiometric RuO2(110) during TPRS for initial CH3OH coverages below ∼0.33 ML (monolayer), and that partial oxidation to mainly CH2O becomes increasingly favored with increasing CH3OH coverage from 0.33 to 1.0 ML. We present evidence that an adsorbed CH2O2 species serves as the key intermediate to complete oxidation and that CH2O2 formation is intrinsically facile but becomes limited by the availability of bridging O-atoms on stoichiometric RuO2(110) at initial CH3OH coverages above 0.33 ML. We show that methanol molecules adsorbed in excess of 0.33 ML dehydrogenate to mainly CH2O and desorb during TPRS, with adsorbed CH3O groups mediating the evolution of both CH2O and CH3OH. We find that O-rich RuO2(110) surfaces are also highly active toward methanol oxidation and that selectivity toward the complete oxidation of methanol increases markedly with increasing coverage of on-top O-atoms (Oot) on RuO2(110). Our results demonstrate that CH3OH species adsorbed within Oot-rich domains react efficiently during TPRS, in parallel with reaction of CH3OH adsorbed initially on cus-Ru sites. The data suggests that the facile hydrogenation of Oot atoms and the resulting desorption of H2O at low-temperature (<∼400 K) provides an efficient pathway for restoring reactive O-atoms and thereby promoting complete oxidation of methanol on the O-rich RuO2(110) surface.

Adsorption of alkanes on stoichiometric and oxygen-rich RuO2(110).

We investigated the molecular adsorption of methane, ethane, propane and n-butane on stoichiometric and oxygen-rich RuO2(110) surfaces using temperature-programmed desorption (TPD) and dispersion-corrected density functional theory (DFT-D3) calculations. We find that each alkane adsorbs strongly on the coordinatively-unsaturated Ru (Rucus) atoms of s-RuO2(110), with desorption from this state producing a well-defined TPD peak at low alkane coverage. As the coverage increases, we find that alkanes first form a compressed layer on the Rucus atoms and subsequently adsorb on the bridging O atoms of the surface until the monolayer saturates. DFT-D3 calculations predict that methane preferentially adsorbs on top of a Rucus atom and that the C2 to C4 alkanes preferentially adopt bidentate configurations in which each molecule aligns parallel to the Rucus atom row and datively bonds to neighboring Rucus atoms. DFT-D3 predicts binding energies that agree quantitatively with our experimental estimates for alkane σ-complexes on RuO2(110). We find that oxygen atoms adsorbed on top of Rucus atoms (Oot atoms) stabilize the adsorbed alkane complexes that bind in a given configuration, while also blocking the sites needed for σ-complex formation. This site blocking causes the coverage of the most stable, bidentate alkane complexes to decrease sharply with increasing Oot coverage. Concurrently, we find that a new peak develops in the C2 to C4 alkane TPD spectra with increasing Oot coverage, and that the desorption yield in this TPD feature passes through a maximum at Oot coverages between ∼50% and 60%. We present evidence that the new TPD peak arises from C2 to C4 alkanes that adsorb in upright, monodentate configurations on stranded Rucus sites located within the Oot layer.

Comparison of Different Endodontic Access Cavity Designs on the Fracture Resistance of Tooth in WaveOne Gold and TruNatomy Instrumentation.

Background: An important aspect of the preparation of the access cavity and biomechanical preparation of the root canal is to safeguard as much of the tooth's framework as possible without affecting access and visibility. Objectives: To compare the impact of the conservative design of access preparation and traditional design of access preparation in association with TruNatomy endodontic instrumentation and WaveOne Gold endodontic instrumentation on resistance to fracture by the design of a cavity for endodontic access using finite element analysis. Materials and Methods: Micro-CT radiographic images of 16 human first permanent molars of the mandible were included in the study to create representative finite element analysis computational models. Results: A significant reduction in load for failure after endodontic preparation was observed in TDAP subcategories as compared to specimens with CDAP. However, the reduction in load for failure was comparable in both endodontic instrument systems within the CDAP and TDAP. Conclusion: A significant reduction in load for failure after endodontic preparation was observed in the traditional design of access preparation subcategories as compared to specimens with the conventional design of access preparation.

Correlation Between Radiological and Functional Outcomes Following Operative and Nonoperative Management of Acetabular Fractures: A Prospective Observational Study.

INTRODUCTION: The management of acetabular fractures is a complicated orthopedic procedure that has been advancing with time. Newer radiological tools like CT scans help surgeons to identify and manage these fractures more attentively. The study was conducted to evaluate the clinical and radiographic outcomes in patients with acetabular fractures managed either conservatively or by open reduction and internal fixation. MATERIALS AND METHOD: The study was done on 35 patients aged 18-60 years, with acetabular fractures treated either surgically or conservatively. Clinical scorings and radiological scoring were only taken and noted at three- and six-month intervals using Matta's radiographic scoring and modified Merle d'Aubigne and Postel clinical hip scoring. Clinico-radiological variables and complications were compared between the two groups. The data obtained was subjected to statistical analyses using IBM Statistical Package of Social Sciences (SPSS) 2.0 version software (Chicago, IL, USA) at a level of significance being p<0.05. RESULTS:  Out of a total of 35 patients, 19 were treated surgically and 16 conservatively. In patients belonging to the surgical treatment group, a maximum of 57.9% were aged 40-50 years, whereas the maximum patients (50%) of the conservative treatment group were aged <40 years, with male predominance in both groups. The type of fracture was recorded according to Judet and Letournel in both groups. Merle d'Aubigne's scoring and Matta's hip score were recorded at three and six months in both groups. A positive correlation was seen between radiological and functional outcomes at three and six months, which means that the higher the radiological scoring, the better the functional outcome of the patient managed either conservatively or surgically in the entire cohort. CONCLUSION:  Our study revealed that surgically managed patients had better functional and radiological outcomes than the patients who were conservatively managed at six months of follow-up. However, this is associated with more complications depending on fracture complexity and initial presentation of hip dislocation. The higher the radiological scoring, the better the functional outcome of the patient managed either conservatively or surgically in the entire cohort.

Efficacy of Inclisiran in Patients Having Familial Hypercholesterolemia: Heterozygous Compared to Homozygous Trait, a Systematic Review and Meta-analysis.

OBJECTIVE: To find out whether inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups. METHODS: We conducted the systematic review and meta-analysis of ORION clinical trials. PubMed, Embase, and Clinicaltrials.gov databases were searched for the relevant studies. Atheroscalerotic parameters considered for our objective were low-density lipoprotein cholesterol, total cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B, and nonhigh-density lipoprotein cholesterol. Primary outcomes were the percentage difference in atheroscalerotic parameters at follow-up relative to baseline values. Our study examined these primary outcomes to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by the Cochrane risk of bias tool. Meta-analysis was performed when at least 2 studies reported on the same variable. RESULTS: Four ORION clinical trials provided the data related to the mean difference in the atheroscalerotic parameters at follow-up relative to baseline, of HeFH and HoFH patient populations, after administration of 300 mg inclisiran subcutaneously. We pooled together these mean differences for each group and applied a statistical test to analyze if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in low-density lipoprotein cholesterol (HeFH: -48.62%; HoFH: -9.12%; P < 0.05), total cholesterol (HeFH: -30.31%; HoFH: -11.50%; P < 0.05), apolipoprotein (HeFH: -39.97%; HoFH: -14.68%; P < 0.05), and nonhigh-density lipoprotein (HeFH: -44.51%; HoFH: -12.22%; P < 0.05) between HeFH and HoFH groups. However, the difference in pooled mean difference in PCSK9 values (HeFH: -68.41%; HoFH: -56.25%; P = 0.2) between HeFH and HoFH groups was statistically insignificant. Studies were of high quality. CONCLUSIONS: There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.

Phase 3 RCT comparing docetaxel-platinum with docetaxel-platinum-5FU as neoadjuvant chemotherapy in borderline resectable oral cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.

Predicting Corrosion Damage in the Human Body Using Artificial Intelligence: In Vitro Progress and Future Applications.

Artificial intelligence (AI) is used in the clinic to improve patient care. While the successes illustrate AI's impact, few studies have led to improved clinical outcomes. In this review, we focus on how AI models implemented in nonorthopedic fields of corrosion science may apply to the study of orthopedic alloys. We first define and introduce fundamental AI concepts and models, as well as physiologically relevant corrosion damage modes. We then systematically review the corrosion/AI literature. Finally, we identify several AI models that may be implemented to study fretting, crevice, and pitting corrosion of titanium and cobalt chrome alloys.

Incurable advanced salivary gland tumours: a retrospective analysis and peek into the perplexing clinical and molecular intricacies from a tertiary care centre in India.

Background: Salivary gland tumours are rare cancers with variable course and prognosis. There is a paucity of data, especially for the advanced stages. Materials and methods: This is a retrospective analysis carried out in our institute. All patients seeking treatment for incurable advanced salivary gland tumours from October 2018 to September 2022 were included. Relevant clinical data were collected and appropriate statistical analysis was applied. Results: 30 patients were included in the analysis. The parotid gland was the most common site of origin (73%). Adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC) were equally (37%) the most common pathological subtypes. The majority of patients were males (73%) and lungs (57%) were the most common site of metastases. On molecular analysis, SDC had high rates of androgen receptor (AR) (90%) and human epidermal growth factor receptor 2 (HER2) (55%) positivity. Mucoepidermoid carcinoma (MEC) had AR and HER2 positivity rates of 17% and 20%, respectively, while for ACC it was even lower. A variety of treatment regimens including hormonal therapy, anti-HER2 targeted therapy and chemotherapy were used in first-line treatment. With an overall response rate (ORR) of 10/21 (48%), only 9/21 (43%) went on to receive second-line treatment with an ORR of 4/9 (44%). The progression-free survival (PFS) with first-line treatment (PFS1) was a median of 5 months. The median PFS1 was worst for MEC. The median overall survival (OS) was 10 months. Median OS for ACC, SDC and MEC were 11, 10 and 7 months, respectively. At 24 months, ACC had much higher survival (50%) than others (10%) indicating a proportion of ACC with an indolent course. Conclusion: Our analysis highlights the variable disease biology of advanced salivary gland tumours and throws light on the various possible treatment targets and strategies. Molecular profiling and advancement in targeted therapies are expected to increase survival in this group of rare cancers.

Low-Dose Immunotherapy in Head and Neck Cancer: A Randomized Study.

PURPOSE: The regimens approved for the treatment of advanced head and neck squamous cell carcinoma are accessible to only 1%-3% of patients in low- and middle-income countries because of their cost. In our previous study, metronomic chemotherapy improved survival in this setting. Retrospective data suggest that a low dose of nivolumab may be efficacious. Hence, we aimed to assess whether the addition of low-dose nivolumab to triple metronomic chemotherapy (TMC) improved overall survival (OS). METHODS: This was a randomized phase III superiority study. Adult patients with recurrent or newly diagnosed advanced head and neck squamous cell carcinoma being treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0-1 were eligible. Patients were randomly assigned 1:1 to TMC consisting of oral methotrexate 9 mg/m2 once a week, celecoxib 200 mg twice daily, and erlotinib 150 mg once daily, or TMC with intravenous nivolumab (TMC-I) 20 mg flat dose once every 3 weeks. The primary end point was 1-year OS. RESULTS: One hundred fifty-one patients were randomly assigned, 75 in TMC and 76 in the TMC-I arm. The addition of low-dose nivolumab led to an improvement in the 1-year OS from 16.3% (95% CI, 8.0 to 27.4) to 43.4% (95% CI, 30.8 to 55.3; hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P = .0036). The median OS in TMC and TMC-I arms was 6.7 months (95% CI, 5.8 to 8.1) and 10.1 months (95% CI, 7.4 to 12.6), respectively (P = .0052). The rate of grade 3 and above adverse events was 50% and 46.1% in TMC and TMC-I arms, respectively (P = .744). CONCLUSION: To our knowledge, this is the first-ever randomized study to demonstrate that the addition of low-dose nivolumab to metronomic chemotherapy improved OS and is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.