Long-term swallow outcomes and factors affecting swallowing dysfunction and quality of life among oral cancer patients: a prospective observational study.

BACKGROUND: Oral cancer is one of the most common cancers among the Indian population. India bears the most burden of oral cancer globally. Impairment of swallowing function is often seen after treatment for oral cancer. The oral phase of swallowing is disrupted in patients undergoing resection for oral cancer. The primary purpose of this study was to evaluate the long-term swallowing outcomes of oral cancer patients using a patient-reported outcome questionnaire. METHODOLOGY: All consecutive oral cancer patients in the cT2-T4 category undergoing curative-intent surgery and reconstruction at our institute from March 2020 to March 2022 were included in the study. The Sydney Swallow questionnaire (SSQ) and functional oral intake scale (FOIS) assessed swallowing outcomes six months after definitive treatment. WHO BREF quality-of-life questionnaire was used to assess health-related quality of life. RESULTS: A total of seventy patients with oral cancer were included. The median age was 49 years. The majority of them were males (90%). Tumors with cT4 constituted 62%; the rest, 48%, were cT2 and cT3 categories. The bulk of them were buccoalveolar tumors (64.3%. Almost two-thirds of the patients received multimodal treatment. Trismus and xerostomia were at 46% and 88%, respectively. The mean SSQ score was 257.4 ± 99.1. Swallowing outcomes are affected by T stage (p = 0.01), extent of resection (p = 0.01), multimodality treatment (p < 0.01), trismus (p = 0.05), and xerostomia (p = 0.01). Almost 69% of them required special food preparation for swallowing (FOIS 4&5). Patients with buccoalveolar disease (p = 0.05) had significantly poor quality of life. CONCLUSION: An advanced stage with extensive resection and receiving multimodal treatment has adverse swallowing outcomes. Post-treatment trismus and xerostomia also significantly affected swallowing results.

Perioperative Management for Functional Ganglioneuroma in a 2-Year-Old Child with Multiple Congenital Defects and COVID-19: A Case Report.

Unlike neuroblastoma, ganglioneuroma is a rare entity in children younger than 7 years of age. Further, these tumors are mostly inactive endocrinologically with the symptoms of abdominal pain or palpable mass. Unfortunately, when functional, they mimic or occasionally coexist with pheochromocytoma. While perioperative management of pheochromocytoma has evolved, very little is known regarding the periopera- tive management of functioning ganglioneuroma. Hormone secretion due to surgical manipulation and anaesthesia leads to life-threatening complications. The risk further increases when associated with other congenital comorbidities. Furthermore, the corona pandemic, in other words, coronavirus disease 2019 infection, in the perioperative period is another new challenge. We report perioperative management and outcome of a functioning retroperitoneal ganglioneuroma in a 2-year-old child, having a ventricular septal defect, spina bifida occulta, and coronavirus disease 2019. The case also highlights decision-making challenges during the coronavirus disease 2019 pandemic.

Evaluation of the Outcomes of Proximal Femoral Nail Antirotation II in the Treatment of Trochanteric Fracture in Elderly Patients.

Background Intertrochanteric fractures are common injuries among the elderly population and those with osteoporosis. The study was conducted in order to evaluate the outcome of Proximal Femoral Nail Antirotation II (PFN-A2) in the treatment of these fractures in elderly patients. Methods Twenty-five elderly patients (range 60 to 73 years) with trochanteric fractures who were treated with PFN-A2 at Government Medical College Amritsar were included in this prospective observational study. These patients were followed up regularly until six months post-operatively. The functional and radiological evaluations were done at six, 12, 16, and 20 weeks. The functional outcome was evaluated using the Harris Hip Score (HHS). Results The mean age incidence for trochanteric fractures was 64 years. There were no cases of intra-operative and postoperative femoral fractures. The mean operating time was 85.6 minutes. Radiological union was seen in all of the 25 patients. The mean time for fracture union time in our study was 13.8 weeks. The average Harris Hip Score in our study was calculated at three months as 74.3 and at six months as 85.08. The p-value was highly significant (0.001) for this improved outcome. This study found PFN-A2 related secondary varus deformities in 8.0% of the patients (two patients). Only one patient (4%) developed surgical site infection (SSI). Conclusion PFN-A2 provides adequate functional results in terms of fixation and healing. This can be further enhanced by good pre-operative planning, correct technique of entry point, and meticulous placement of implant with a helical blade in both anteroposterior (AP), lateral view, and distal locking and non-acceptance of reduction in varus. A good reduction is required to achieve a good functional outcome. We conclude that the PFN-A2 has the benefit of closed reduction, short operative time, preservation of biology, less soft tissue damage, and early rehab.

Age induced interactions between heart rate variability and systolic blood pressure variability using approximate entropy and recurrence quantification analysis: a multiscale cross correlation analysis.

The purpose of this study is to study the effect of age on the correlation between heart rate variability (HRV) and blood pressure variability (BPV). To meet this end, multi-scale cross correlation (CC) analysis of HRV and systolic blood pressure variability (SBPV) was performed. The Approximate Entropy (ApEn) and Recurrence Quantification Analysis (RQA) derived indices, calculated from RR interval series (RRi) and systolic blood pressure (SBP) series at multiple temporal scales, are the basis of this CC analysis. For the computation of ApEn and RQA indices, the tolerance threshold (r) is chosen by either: (i) selecting any arbitrary value (0.2) within the recommended range (0.1-0.25) times standard deviation (SD) of time series, and (ii) taking the 'r' (ropt) corresponding to maximum ApEn (ApEnmax) as tolerance threshold. It is found that (i) at each time scale (τ), a lower SD is observed when indices are computed using ropt than [Formula: see text] (r0.2), for RRi as well as SBP series, (ii) descriptive indices of RRi are found significant (p < 0.05) at all scales (τ), however for SBP, these are found insignificant (p > 0.05) at most of the scales, (iii) CC values of descriptive statistics viz., mean and SD are not significant (p > 0.05) irrespective of τ, barring τ = 1, (iv) CC values of ApEn and RQA indices, found using ropt, are found significant (p < 0.05) and provide enhanced stratification at τ = 1, 2 and 3, whereas this significant correlation and strong classification is missing for indices calculated using r0.2, and (v) Lastly as τ increases, ApEn and RQA indices, computed with ropt, reverse their trend but manage to provide significant difference in elder and younger subjects. It is concluded that HRV and SBPV interactions gets altered with age. Descriptive indicators however are not enough to capture these changes. These complex interactions can only be deciphered using complexity-based methods such as approximate entropy and that too at the multiple scale level.

Exploring digital therapeutics: The next paradigm of modern health-care industry.

In this era of 21st century, the most valuable resource is data. Digital technology can generate terabytes of data which has a tremendous potential in the modern-day world. Pharmaceuticals play an essential role in improving and maintaining the health of patients. However, their cost in health-care budget is a major issue. Due to high prevalence and unfavorable consequences, managing chronic and lifestyle disorders has now become areas of major clinical concern globally. Harnessing this digital technology in our overburdened health-care industry can improve the treatment outcome and even replace the existing treatment. Health authorities such as U.S. Food and Drug Administration (USFDA) are also acknowledging their potential. FDA's Center for Devices and Radiological Health has established the "Digital Health Program" which seeks to promote public health and provide continued regulatory clarity by enhancing outreach to digital health customers and developing and implementing regulatory strategies and policies for digital health technologies. The main focus of this article is to give an overview of digital therapeutics (DT), its clinical applications, role of regulators, and challenges ahead along with potential areas for developers and to present an update on major developments and initiatives taken in this field. The most important advantages of DT are that it has direct access to patients, decreases cost of treatment, encourages healthy lifestyle modifications, and can substitute or complement conventional treatments. Many of these models are still in infancy stage, and further research and development is needed to demonstrate their enormous potential in near future. If used judiciously, they can modernize our health-care industry.

Dynamic contact networks of patients and MRSA spread in hospitals.

Methicillin-resistant Staphylococcus aureus (MRSA) is a difficult-to-treat infection. Increasing efforts have been taken to mitigate the epidemics and to avoid potential outbreaks in low endemic settings. Understanding the population dynamics of MRSA is essential to identify the causal mechanisms driving the epidemics and to generalise conclusions to different contexts. Previous studies neglected the temporal structure of contacts between patients and assumed homogeneous behaviour. We developed a high-resolution data-driven contact network model of interactions between 743,182 patients in 485 hospitals during 3,059 days to reproduce the exact contact sequences of the hospital population. Our model captures the exact spatial and temporal human contact behaviour and the dynamics of referrals within and between wards and hospitals at a large scale, revealing highly heterogeneous contact and mobility patterns of individual patients. A simulation exercise of epidemic spread shows that heterogeneous contacts cause the emergence of super-spreader patients, slower than exponential polynomial growth of the prevalence, and fast epidemic spread between wards and hospitals. In our simulated scenarios, screening upon hospital admittance is potentially more effective than reducing infection probability to reduce the final outbreak size. Our findings are useful to understand not only MRSA spread but also other hospital-acquired infections.

Suspected reactivation of extrapulmonary tuberculosis focus after non-medical abuse of anabolic androgenic steroids: a case report.

Background Youth population has a common tendency to use androgenic steroids. The reasons for such abuse vary from performance enhancement to muscle building in order to enhance physical appearance. Such rampant abuse, aided by fitness centers and gym trainers, has a huge risk of side effects such as hepatic dysfunctions and increased risk of infections. Case presentation We report a case of 21-year-old man who started with anabolic steroids, namely testosterone enanthate, nandrolone decanoate and boldenone undecylenate injections, for the purpose of muscle building and strength training at his fitness center. He presented to his family physician after 2 months with upper neck swelling on right side 5 × 4 cm for 15-20 days. He was started on Augmentin 625 mg tablet three times a day for 7 days. On seventh day, swelling persisted, and fine needle aspiration cytology (FNAC) was performed, which was suggestive of granulomatous lesion likely to be tuberculosis. The patient was started with anti-tubercular therapy (ATT) under category A, but swelling did not improve and repeated FNAC was advised. The ATT was withheld and Augmentin tablet was restarted for another 3 days. A revised diagnosis of acute suppurative lymphadenitis was made, and an incision and drainage of the abscess was performed. The patient was started on Amikacin 500 intramuscular injection for 5 days along with faropenem and cefuroxime axetil tablets for 14 days. He initially started recovering but returned with pustular discharge from the incision mark. It was decided to reinitiate the ATT-intensive phase medication for another 2 months. The patient finally recovered with complete healing of the wound. The frequent change of treating physician and misuse of antimicrobials made the diagnosis tougher, contributing to delay in the optimum therapy. Conclusion This case highlights the abuse of multiple steroids together in the form of stacking by a young adult, which leads to a rare serious adverse effect such as suspected tubercular reactivation.

A unified non-linear approach based on recurrence quantification analysis and approximate entropy: application to the classification of heart rate variability of age-stratified subjects.

This paper presents a unified approach based on the recurrence quantification analysis (RQA) and approximate entropy (ApEn) for the classification of heart rate variability (HRV). In this paper, the optimum tolerance threshold (ropt) corresponding to ApEnmax has been used for RQA calculation. The experimental data length (N) of RR interval series (RRi) is optimized by taking ropt as key parameter. ropt is found to be lying within the recommended range of 0.1 to 0.25 times the standard deviation of the RRi, when N ≥ 300. Consequently, RQA is applied to the age stratified RRi and indices such as percentage recurrence (%REC), percentage laminarity (%LAM), and percentage determinism (%DET) are calculated along with ApEnmax, [Formula: see text], [Formula: see text], and an index namely the radius differential (RD). Certain standard HRV statistical indices such as mean RR, standard deviation of RR (or NN) interval (SDNN), and the square root of the mean squared differences of successive RR intervals (RMSSD) (Eur Hear J 17:354-381, 1996) are also found for comparison. It is observed that (i) RD can discriminate between the elderly and young subjects with a value of 0.1151 ± 0.0236 (mean ± SD) and 0.0533 ± 0.0133 (mean ± SD) respectively for the elderly and young subjects and is found to be statistically significant with p < 0.05. (ii) Similar significant discrimination was obtained using [Formula: see text] with a value of 0.1827 ± 0.0382 (mean ± SD) and 0.2248 ± 0.0320 (mean ± SD) (iii) other significant indices were found to be %REC, %DET, %LAM, SDNN, and RMSSD; however, ApEnmax was found to be insignificant with p > 0.05. The above features of RRi time series were tested for classification using support vector machine (SVM) and multilayer perceptron neural network (MLPNN). Higher classification accuracy was achieved using SVM with a maximum value of 99.71%. Graphical abstract.

Unique size and shape-dependent uptake behaviors of non-spherical nanoparticles by endothelial cells due to a shearing flow.

The size and shape of nanoparticle (NP) drug carriers can potentially be manipulated to increase the drug delivery efficacy because of their effects on particle margination and interactions with various cells in vivo. It is found in this work that the presence of a physiologically relevant shearing flow rate results in very different size and shape-dependent uptake behavior of negatively charged, non-spherical polyethylene glycol (PEG) hydrogel NPs by endothelial cells (ECs) cultured in a microchannel compared to uptake of either identical NPs in static culture or spherical particles in a shear flow. In particular, larger rod- and disk-shaped PEG NPs show more uptake than smaller ones, opposite to the size effect observed for spherical particles in a flow. Moreover, the trend observed in this dynamic uptake experiment also differs from that reported for uptake of similar PEG NPs by ECs in a static culture, where the smaller disks were found to be uptaken the most. These differences suggest that the increasing rotational and tumbling motions of larger-size non-spherical NPs in the flow play a dominant role in NP margination and cell interaction, compared to Brownian motion, gravity, and cell membrane deformation energy. These findings suggest that the coupling between NP geometry and shear flow is an important factor that needs to be accounted for in the design of the size and shape of nanocarriers.

Effect of shape, size, and aspect ratio on nanoparticle penetration and distribution inside solid tissues using 3D spheroid models.

Efficient penetration and uniform distribution of nanoparticles (NPs) inside solid tissues and tumors is paramount to their therapeutic and diagnostic success. While many studies have reported the effect of NP size and charge on intratissue distribution, role of shape, and aspect ratio on NP transport inside solid tissues remain unclear. Here experimental and theoretical studies are reported on how nanoscale geometry of Jet and Flash Imprint Lithography-fabricated, polyethylene-glycol-based anionic nanohydrogels affect their penetration and distribution inside 3D spheroids, a model representing the intervascular region of solid, tumor-like tissues. Unexpectedly, low aspect ratio cylindrical NPs (H/D ≈0.3; disk-like particles, 100 nm height, and 325 nm diameter) show maximal intratissue delivery (>50% increase in total cargo delivered) and more uniform penetration compared to nanorods or smaller NPs of the same shape. This is in contrast to spherical NPs where smaller NP size resulted in deeper, more uniform penetration. Our results provide fundamental new knowledge on NP transport inside solid tissues and further establish shape and aspect ratio as important design parameters in developing more efficient, better penetrating, nanocarriers for drug, or contrast-agent delivery.

Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms.

Size, surface charge, and material compositions are known to influence cell uptake of nanoparticles. However, the effect of particle geometry, i.e., the interplay between nanoscale shape and size, is less understood. Here we show that when shape is decoupled from volume, charge, and material composition, under typical in vitro conditions, mammalian epithelial and immune cells preferentially internalize disc-shaped, negatively charged hydrophilic nanoparticles of high aspect ratios compared with nanorods and lower aspect-ratio nanodiscs. Endothelial cells also prefer nanodiscs, however those of intermediate aspect ratio. Interestingly, unlike nanospheres, larger-sized hydrogel nanodiscs and nanorods are internalized more efficiently than their smallest counterparts. Kinetics, efficiency, and mechanisms of uptake are all shape-dependent and cell type-specific. Although macropinocytosis is used by both epithelial and endothelial cells, epithelial cells uniquely internalize these nanoparticles using the caveolae-mediated pathway. Human umbilical vein endothelial cells, on the other hand, use clathrin-mediated uptake for all shapes and show significantly higher uptake efficiency compared with epithelial cells. Using results from both upright and inverted cultures, we propose that nanoparticle internalization is a complex manifestation of three shape- and size-dependent parameters: particle surface-to-cell membrane contact area, i.e., particle-cell adhesion, strain energy for membrane deformation, and sedimentation or local particle concentration at the cell membrane. These studies provide a fundamental understanding on how nanoparticle uptake in different mammalian cells is influenced by the nanoscale geometry and is critical for designing improved nanocarriers and predicting nanomaterial toxicity.

Long-term treatment with intravenous bisphosphonates in metastatic breast cancer: a retrospective study.

Bisphosphonates are important therapies used to reduce the risk of skeletal-related events in patients with bone metastases from breast cancer (BC). This retrospective cohort study evaluated the incidence of osteonecrosis of the jaw (ONJ) and renal impairment in women (n = 221) with bone metastases from BC treated with intravenous bisphosphonates from January 1999 to June 2008. In the long-term cohort, 159 patients received pamidronate (n = 9), zoledronic acid (n = 110), or both (n = 40) for ≥24 months. The comparator group consisted of patients treated with intravenous bisphosphonates for 12-23 months (n = 62). After 39 months' median follow-up, six of 159 patients developed ONJ (3.8%; median 38.5 treatment cycles and 44 months' exposure) in the long-term cohort. Of patients who developed ONJ, 50% resumed intravenous bisphosphonates after a 12-month treatment holiday. Renal impairment developed in 19 patients in the long-term cohort (11.9%; median 26 treatment cycles and 26 months' exposure). Of these 19 patients, 11 (57.9%) recovered baseline renal function and seven (36.7%) showed partial recovery. After modification of the intravenous bisphosphonate regimen, 17 of 19 patients (89.4%) resumed therapy. Of the 62 patients in the comparator cohort, one patient developed ONJ (1.6%) and six developed renal impairment (9.7%). Similar incidence rates of ONJ and renal impairment were observed for the long-term and comparator cohorts. Times to ONJ or renal impairment also were similar across intravenous bisphosphonate type. Long-term (≥24 months) intravenous bisphosphonate use in metastatic BC is well tolerated, with low incidences of ONJ and renal impairment.

Scalable imprinting of shape-specific polymeric nanocarriers using a release layer of switchable water solubility.

There is increasing interest in fabricating shape-specific polymeric nano- and microparticles for efficient delivery of drugs and imaging agents. The size and shape of these particles could significantly influence their transport properties and play an important role in in vivo biodistribution, targeting, and cellular uptake. Nanoimprint lithography methods, such as jet-and-flash imprint lithography (J-FIL), provide versatile top-down processes to fabricate shape-specific, biocompatible nanoscale hydrogels that can deliver therapeutic and diagnostic molecules in response to disease-specific cues. However, the key challenges in top-down fabrication of such nanocarriers are scalable imprinting with biological and biocompatible materials, ease of particle-surface modification using both aqueous and organic chemistry as well as simple yet biocompatible harvesting. Here we report that a biopolymer-based sacrificial release layer in combination with improved nanocarrier-material formulation can address these challenges. The sacrificial layer improves scalability and ease of imprint-surface modification due to its switchable solubility through simple ion exchange between monovalent and divalent cations. This process enables large-scale bionanoimprinting and efficient, one-step harvesting of hydrogel nanoparticles in both water- and organic-based imprint solutions.

Biological considerations and clinical applications of new HER2-targeted agents.

Over the past two decades, since the discovery of the human EGF receptor 2 (HER2) oncogene, the oncoprotein has become one of the best known and intensively studied tumor targets in oncology. In fact, laboratory findings were the basis for clinical proof-of-principle studies, whose results not only confirmed the relationship between gene amplification and an aggressive tumor phenotype but also demonstrated that the poor prognosis associated with receptor overexpression could be improved. Indeed, the success in treating patients with HER2-positive breast cancer extends to those with early as well as advanced disease. Nonetheless, not all tumors respond to treatment targeting the receptor; disease progression also occurs after initially responding to anti-HER2 therapy. This article focuses on the biology of HER2 and three novel agents currently in clinical trials that target HER2 beyond disease progression.

Transesophageal echocardiographic diagnosis of aortic arch-left innominate vein fistula.

We present a patient with aortic arch-left innominate vein (LIV) fistula diagnosed by transesophageal echocardiography. Also, an interrupted linear echo was noted within the dilated LIV with flow signals moving across the area of interruption, suggestive of left innominate vein pseudo-aneurysm or dissection. The patient subsequently underwent successful surgical repair of the fistula.

Live three-dimensional transthoracic echocardiographic assessment of transcatheter closure of atrial septal defect and patent foramen ovale.

We report the usefulness of live three-dimensional transthoracic echocardiography in the accurate assessment of the morphology and efficacy of Amplatzer transcatheter devices used for closure of atrial septal defect and patent foramen ovale.

Images in geriatric cardiology. Usefulness of live three-dimensional transthoracic echocardiography in aortic valve stenosis evaluation.

Aortic valve stenosis (AS) severity can be estimated by various modalities. Due to some of the limitations of the currently available methods, the usefulness of live three-dimensional transthoracic echocardiography (3D TTE) in the assessment of AS was explored. Live 3D TTE was able to visualize the aortic valve orifice in all 11 patients studied. Live 3D TTE correctly estimated the severity of AS in all 10 patients in whom AS severity could be evaluated at surgery. These included eight patients with severe AS and two with moderate AS. Two of these 10 patients with AS had associated hypertrophic cardiomyopathy and underwent myectomy at the time of aortic valve replacement. Aortic valve orifice area measurements by live 3D TTE correlated well with intraoperative three-dimensional transesophageal echocardiographic reconstruction measurements (r=0.85) but not as well with two-dimensional transesophageal echocardiography measurements (r=0.64). Live 3D TTE measurements of the aortic valve orifice area also did not correlate well with two-dimensional transthoracic echocardiography measurements (r=0.46) but the number of patients studied with two-dimensional transthoracic echocardiography was smaller (only seven) and four of these did not undergo two-dimensional transthoracic echocardiography at the authors' institution. Altogether, four patients with severe AS by live 3D TTE, and subsequently confirmed at surgery, were misdiagnosed as having moderate AS by two-dimensional transthoracic echocardiography. Because it is completely noninvasive and views the aortic valve in three dimensions, 3D TTE could be a useful complement to the existing modalities in the evaluation of AS severity.

Transpharyngeal ultrasound detection of carotid body paraganglioma.

We report a patient in whom a right carotid body paraganglioma was delineated using a transpharyngeal approach during a transesophageal echocardiographic (TEE) study. Color Doppler-guided pulsed-Doppler interrogation of the right internal carotid artery in the tumor region, revealed high maximum systolic and maximum diastolic velocities of 1.5 m/s and 1.0 m/s, respectively, suggestive of tumor compression.

Live three-dimensional echocardiography of the human fetus.

The purpose of this study was to investigate the feasibility of using a new three-dimensional ultrasound system to perform fetal echocardiographic examination in real time. The device consisted of a Philips Sonos 7500 (Andover, MA) ultrasound system and a 4 MHz, 4X matrix transducer. The study was approved by the Institutional Review Board and was performed with the informed consent of the mother. The study population consisted of 12 singleton fetuses with gestational ages of 16-37 weeks. Of these, ten fetuses had normal cardiac anatomy, one had complete atrioventricular septal defect, and the other a thickened tricuspid valve. The system allowed comprehensive visualization of fetal cardiac anatomy and color Doppler flow unattainable by two-dimensional approaches. This preliminary investigation suggests that live three-dimensional fetal echocardiography could be a significant tool for prenatal diagnosis and assessment of congenital heart disease in the human fetus.