Proliferative verrucous leukoplakia/multifocal leukoplakia in patients with and without oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF) and proliferative verrucous leukoplakia (PVL) are established as oral potentially malignant disorders. Dual pathology of the two conditions is not commonly encountered in clinical practice. This study aims to present a case series of multifocal leukoplakia in patients with and without OSF to outline the clinical behavior and challenges in the management of this high-risk group in clinical practice. MATERIAL AND METHODS: We retrospectively analyzed cases of six Indian patients (four with OSF) managed over a period of 5.5 to 13 years at the Government Dental College, Nagpur. Patient data consisting of age, gender, medical history, habits, clinical findings, and biopsy reports were recorded at the initial visit. During follow-up visits, the clinicopathological data were reassessed. When surgical intervention failed to arrest the disease or when surgery was contraindicated metronomic therapy with Folitrax 15 mg once a week and Celecoxib 100mg twice daily was initiated. RESULTS: All patients developed PVL after the initial pathology diagnosis of OSF or oral leukoplakia. Initial lesions were either homogenous or non-homogenous leukoplakia. All patients developed multiple recurrences, regional or systemic metastasis. Despite thorough interventions, the patients died of, or with the disease. CONCLUSIONS: The occurrence of two or more oral potentially malignant disorders poses challenges in patient management and possibly presents a higher risk of malignant transformation. More clinical trials are necessary to assess the benefits of metronomic therapy for patients diagnosed with aggressive PVL concurrently found with OSF.

Core content for venous and Lymphatic Medicine: 2022 revision.

The core content for a medical specialty outlines the scope of the discipline as well as the categories of knowledge considered essential to practice in the field. It provides a template for the development of curricula for medical school, graduate, and postgraduate education, as well as for creating certification standards. Venous and Lymphatic Medicine (VLM) is a specialty that has benefitted from contributions from specialists from several medical disciplines. Optimally, the societies, boards, and residency review committees representing these disciplines would uniformly recognize the scope of VLM to develop education and assessment standards to allow training and identification of qualified practitioners. In order to inform the standard setting bodies and other stakeholders of the current scope of VLM, a task force of VLM experts from cardiology, dermatology, emergency medicine, general surgery, interventional radiology, vascular medicine, and vascular surgery was formed to revise a 2014 consensus document defining the core content of the specialty of VLM.

A case of prosthetic hip infection and abscess caused by Trueperella bernardiae.

Trueperella bernardiae is a skin flora organism with few reported cases of pathology. Most cases have been described in urinary tract infections and skin and soft-tissue infections. We present the first known case of T. bernardiae as a causative agent of a prosthetic hip infection with subsequent hip abscess.

Drug Survival of IL-12/23, IL-17 and IL-23 Inhibitors for Psoriasis Treatment: A Retrospective Multi-Country, Multicentric Cohort Study.

BACKGROUND: Drug survival analysis of biologic agents in psoriasis is of extreme importance, as it allows not only the evaluation of objective clinical outcomes (such as effectiveness and safety) but also of factors that are associated with patients' adherence to treatment. The aim of this study was to evaluate and compare the drug survival of the most recent biologic agents approved for the treatment of moderate-to-severe psoriasis-ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and risankizumab-and to identify clinical predictors that can influence the drug survival of these drugs. METHODS: This retrospective multicentric cohort study from 16 dermatology centers in Portugal, Spain, Italy, Switzerland, Czech Republic, Canada, and the United States included patients that started IL-12/23, IL-17 (IL-17A and IL-17R) and IL-23 inhibitors for the treatment of psoriasis between January 1, 2012 and December 31, 2019. Survival analysis was performed using a Kaplan-Meier estimator, to obtain descriptive survival curves, and proportional hazard Cox regression models. RESULTS: A total of 3312 treatment courses (total patients: 3145) were included in the study; 1118 (33.8%) with an IL-12/23 inhibitor (ustekinumab), 1678 (50.7%) with an IL-17 inhibitor [911 (27.5%) on secukinumab, 651 (19.7%) on ixekizumab, 116 (3.5%) on brodalumab], and 516 (15.5%) with an IL-23 inhibitor [398 (12.0%) on guselkumab, 118 (3.5%) on risankizumab]. At 18 months, the cumulative probability of survival was 96.4% for risankizumab, 91.1% for guselkumab, 86.3% for brodalumab, 86.1% for ustekinumab, 82.0% for ixekizumab, and 79.9% for secukinumab. Using ustekinumab as reference, drug survival of guselkumab was higher (HR 0.609; 95% CI 0.418-0.887) and that of secukinumab was lower (HR 1.490; 95% CI 1.257-1.766). In the final multivariable model, secukinumab, female sex, higher BMI, and prior exposure to biologic agents significantly increased the risk of drug discontinuation, whereas risankizumab was protective. CONCLUSION: In this multinational cohort with 8439 patient-years of follow-up, the cumulative probability of drug survival for all drugs was >79% at 18 months. Prescribed biologic, female sex, higher BMI, and previous exposure to biologic agents were predictors of drug discontinuation. Drug survival of guselkumab and risankizumab was higher than that of ustekinumab, and secukinumab was lower.

A case-control study of epidemiological factors associated with leptospirosis in South Gujarat region.

BACKGROUND: The current study was planned to identify the epidemiological factors associated with leptospirosis in South Gujarat region using neighborhood controls. METHODS: A total of 100 cases of leptospirosis occurred in South Gujarat region during the year 2012 were selected using simple random sampling. Three neighbors of the selected cases formed the controls (n = 300). A pretested structured questionnaire was used for data collection and data were analyzed using Epi Info 2007. RESULTS: There was significant association of illiteracy (odds ratio [OR] =1.82, 95% confidence interval [CI] =1.14-2.89), working in waterlogged fields during the reference season (OR = 4.6, 95% CI = 1.6-17.9), swimming/bathing in canals, open air defecation practices, storage of cow dung in or surrounding house, residence in the house made up of cow dung walls, households with access of food to rodents, injuries over hands/foot during the endemic season (OR = 3, 95% CI = 1.8-4.8), and history of skin disease during the endemic season (OR = 4.2, 95% CI = 2-8.5), with leptospirosis. Only 10% of individuals had gumboots for protection. A total of 83 (83%) cases and 240 (80%) controls had taken oral doxycycline chemoprophylaxis (P > 0.05). Cases had taken chemoprophylaxis for a median 4 weeks (range: 1-8) while controls had taken the same for median 8 weeks (range = 1-8) (P < 0.002). CONCLUSIONS: Although the commonly established factors appear to be associated with leptospirosis, the role of host factors seems to play a more important role in determining susceptibility to leptospirosis in exposed individuals.

A rabbit model of cerebral microembolic signals for translational research: preclinical validation for aspirin and clopidogrel.

UNLABELLED: Essentials Microembolic signal (MES) is an independent predictor of stroke risk in patients. A rabbit model of cerebral microembolic signals was established. Therapeutic efficacy was demonstrated for aspirin and clopidogrel on microembolic signals. Potential translational value of this preclinical model of MES was demonstrated. SUMMARY: Objectives Cerebral microembolic signals (MESs) detected by transcranial Doppler (TCD) ultrasound constitute an independent predictor of stroke risk and prognosis. The aim of this study was to develop a novel preclinical model of MESs to facilitate translational research. Methods A clinical TCD ultrasound machine was used to detect MESs in the cerebral circulation of New Zealand White rabbits. Technical feasibility was assessed for the measurement of MESs in the middle cerebral artery (MCA) by TCD. FeCl3 -induced carotid arterial thrombosis was optimized for the generation of endogenous microemboli. Ascending doses of two antithrombotic agents (aspirin and clopidogrel) were evaluated individually and in combination for their effects on both arterial thrombosis and MESs in a 30% FeCl3 -induced carotid arterial thrombosis model, along with ex vivo functional assays. Results Dose-dependent FeCl3 -induced arterial thrombosis studies showed that 30% FeCl3 resulted in the most consistent and reproducible MESs in the MCA (3.3 ± 0.7 MESs h(-1) ). Ascending-dose studies showed that the effective doses for 50% inhibition (ED50 ) of thrombus formation, based on integrated blood flow and thrombus weight, respectively, were 3.1 mg kg(-1) and 4.2 mg kg(-1) orally for aspirin, and 0.3 mg kg(-1) and 0.28 mg kg(-1) orally for clopidogrel. The ED50 values for MES incidence were 12.7 mg kg(-1) orally for aspirin, and 0.25 mg kg(-1) orally for clopidogrel. Dual treatment with aspirin (5 mg kg(-1) ) and clopidogel (0.3 mg kg(-1) ) resulted in significant reductions in cerebral MESs (P < 0.05) as compared with monotherapy with either agent. Conclusions Our study demonstrated the successful establishment of the MES model in rabbits, and it may provide translational value for MESs and ischemic stroke research.

Coming Up Short: Risks of Bias in Assessing Psychological Outcomes in Growth Hormone Therapy for Short Stature.

CONTEXT: Two often cited assumptions for treating children with GH are that short stature (SS), as an isolated physical characteristic, is associated with psychosocial morbidity and that GH treatment may increase height and improve psychological adjustment. Findings across studies regarding the psychological consequences associated with GH management of children with SS are variable and frequently contradictory. The purpose of this systematic review is to evaluate the degree to which any conclusions about the relative risks or benefits of GH treatment on psychological outcomes can be made based on the published literature. EVIDENCE ACQUISITION: Electronic databases were searched for randomized clinical trials and nonrandomized studies, published between 1958-2014, in which GH was administered for management of children with SS and psychosocial, cognitive, academic, or health-related quality of life outcomes were assessed. Methodological quality of each study was assessed using the Cochrane Collaboration's tool for assessing risk of bias. EVIDENCE SYNTHESIS: Eighty studies were evaluated. No studies were rated as having a low risk of bias, the risk of bias was unclear in seven study outcome areas, and the remaining studies were judged as having a high risk of bias. CONCLUSIONS: The high risk of bias present in the majority of the literature on GH treatment effects on psychological outcomes (in particular, lack of blinding) substantially weakens confidence in their results. This may serve to explain the variability of findings for these outcomes across studies.

Prospective study of outcomes of surgically treated larynx and hypopharyngeal cancers.

OBJECTIVE: To determine the morbidity and survival of surgically treated locally advanced carcinoma larynx and hypopharynx in a tertiary referral center in South India, a prospective cohort study was carried out. MATERIALS AND METHODS: Patients who had undergone laryngectomy or laryngopharyngectomy from January, 2006 to January, 2011 at our institute were prospectively studied for factors affecting morbidity tumor recurrence and disease free survival (DFS). DFS was calculated for the whole group and for the larynx and hypopharynx cancer subgroups separately, using Kaplan Meir Method and the survival differences of the larynx and hypopharynx groups and between salvage and primary surgical cases were evaluated using the Cox's regression scale . RESULTS: A total of 154 patients with ages ranging from 23 to 78 (mean 56.3 + standard deviation 9.2) were studied, which included 145 males and 9 females. Pre-operative tracheostomy and previous radiotherapy were the most significant factors contributing to post-operative morbidity. Survival difference between the larynx and hypopharynx cancers was statistically significant and the DFS was significantly affected by primary site wound infection, primary site margin and node positivity. CONCLUSION: The results of laryngectomy can be optimized by "proper case selection and morbidity risk assessment".

Validation of a photogrammetric technique for computing equine hoof volume.

Assessment of equine foot conformation is often based on linear and angular measurements performed on lateral digital photographs. However, quantification of external foot conformation requires more comprehensive assessments to capture the shape of the entire foot. Volumetric measurements of the hoof capsule represent a summary measure quantifying foot shape. The aim of this study was to develop a method for computation of virtual foot models from digital foot images allowing precise and accurate volumetric measurements. This photogrammetric technique was then assessed for the characterization of foot volume changes associated with foot trimming. Using the technique, three different photographers imaged feet from 18 cadavers at different time points and one analyst processed their images to generate virtual computer models. Volumetric measurements were obtained from these models to determine their precision in the context of 'Photographer', 'Time' and the effect of 'Trimming'. Computed tomographic (CT) imaging was used to assess the accuracy of the photogrammetric method. Pre-trim photogrammetric measurements showed excellent precision and accuracy and the results did not depend on the person acquiring the images. The accuracy of post-trim photogrammetric measurements deteriorated in comparison with the average differences measured by CT imaging (19 cm(3)). Precise volumetric measurements were obtained using the photogrammetric method, but average differences in foot volume after trimming as measured by CT imaging are likely too small to be detected with confidence.

Pre-operative prediction of a right non-recurrent laryngeal nerve by computed tomography.

OBJECTIVE: This paper reports a case of a non-recurrent laryngeal nerve which was accurately predicted pre-operatively using computed tomography. CASE REPORT: A 61-year-old man presented with papillary thyroid carcinoma with lymph node metastasis. Computed tomography scans of the neck and chest revealed an ill-defined, hypoattenuating nodule in the right lobe of the thyroid gland, with few upper paratracheal and prevascular nodes, and clear lung fields. The retro-oesophageal course of the right subclavian artery, which was arising from the distal portion of the arch of aorta, was also incidentally revealed in the computed tomography scan. A barium swallow further confirmed the presence of a retro-oesophageal subclavian artery. Total thyroidectomy was performed, with right neck dissection and central compartment clearance. This was carried out with the presence of a non-recurrent laryngeal nerve in mind, and the nerve was accurately localised and preserved. CONCLUSION: To our knowledge this is the first report in the world literature of accurate pre-operative incidental imaging of the right non-recurrent laryngeal nerve in a case of metastatic thyroid cancer, and the subsequent use of computed tomography to guide surgical navigation.

Presynaptic inhibition of the release of multiple major central nervous system neurotransmitter types by the inhaled anaesthetic isoflurane.

BACKGROUND: Presynaptic effects of general anaesthetics are not well characterized. We tested the hypothesis that isoflurane exhibits transmitter-specific effects on neurotransmitter release from neurochemically and functionally distinct isolated mammalian nerve terminals. METHODS: Nerve terminals from adult male rat brain were prelabelled with [(3)H]glutamate and [(14)C]GABA (cerebral cortex), [(3)H]norepinephrine (hippocampus), [(14)C]dopamine (striatum), or [(3)H]choline (precursor of [(3)H]acetylcholine; striatum). Release evoked by depolarizing pulses of 4-aminopyridine (4AP) or elevated KCl was quantified using a closed superfusion system. RESULTS: Isoflurane at clinical concentrations (<0.7 mM; ~2 times median anaesthetic concentration) inhibited Na(+) channel-dependent 4AP-evoked release of the five neurotransmitters tested in a concentration-dependent manner. Isoflurane was a more potent inhibitor [expressed as IC(50) (SEM)] of glutamate release [0.37 (0.03) mM; P<0.05] compared with the release of GABA [0.52 (0.03) mM], norepinephrine [0.48 (0.03) mM], dopamine [0.48 (0.03) mM], or acetylcholine [0.49 (0.02) mM]. Inhibition of Na(+) channel-independent release evoked by elevated K(+) was not significant at clinical concentrations of isoflurane, with the exception of dopamine release [IC(50)=0.59 (0.03) mM]. CONCLUSIONS: Isoflurane inhibited the release of the major central nervous system neurotransmitters with selectivity for glutamate release, consistent with both widespread inhibition and nerve terminal-specific presynaptic effects. Glutamate release was most sensitive to inhibition compared with GABA, acetylcholine, dopamine, and norepinephrine release due to presynaptic specializations in ion channel expression, regulation, and/or coupling to exocytosis. Reductions in neurotransmitter release by volatile anaesthetics could contribute to altered synaptic transmission, leading to therapeutic and toxic effects involving all major neurotransmitter systems.

Chromosomal aberrations in 2000 couples of Indian ethnicity with reproductive failure.

Constitutional chromosomal aberrations contribute to infertility and repeated miscarriage leading to reproductive failure in couples. These aberrations may show no obvious clinical manifestations and remain undetected across multiple generations. However, infertility or recurrent spontaneous pregnancy loss, and/or genotypic/phenotypic aberrations may be manifested in the progeny during gametogenesis. The current study was a retrospective analysis to examine the chromosomal aberrations and prevalence in 2000 couples of Indian ethnicity with reproductive failure. Cytogenetic analysis via conventional G-band karyotyping analysis was carried out on phytohaemagglutinin stimulated peripheral blood lymphocytes, cultured in RPMI1640 medium. The chromosomes were enumerated as per International System for Human Cytogenetic Nomenclature at 500-550 band resolution, and recorded in the screening sheets. Chromosomal aberrations were detected in a total of 110 (2.78%) couples, with structural chromosomal aberrations in 88 cases including reciprocal translocations in 56 cases, Robertsonian translocations in 16 cases, inversions in eight cases, deletions in three cases, derivative chromosomes in five cases and numerical chromosome aberrations in 23 cases. The study emphasizes the importance of cytogenetic work up in both the partners associated with a history of reproductive failure. Genetic counselling with an option of prenatal diagnosis should be offered to couples with chromosomal aberrations.

Effect of chilling on sox2, sox3 and sox19a gene expression in zebrafish (Danio rerio) embryos.

Zebrafish embryos have not been cryopreserved due to their structural limitations. Although embryo survival rates have been used as the measured outcome for most of the cryopreservation protocols studied, there are very limited data available at the molecular level. This study focused on the effect of chilling and subsequent warming on gene expression of sox2, sox3 and sox19a which play vital roles in the development of zebrafish embryos. A quantitative RT-PCR approach was used to investigate gene expression following chilling at 0°C for up to 180 min. The effect on gene expression was also studied during a 180 min warming period after chilling for 30 or 60 min. There were significant decreases in sox2 (up to 4-fold) and sox3 (up to 3-fold) expressions following chilling. Significant increases in gene expressions of sox2 (up to 2-fold), sox3 (up to 33-fold) and sox19a (up to 25-fold) were observed during warming in the embryos that had been chilled for 30 min. Similarly, significant increases were observed in sox2 (up to 3-fold) and sox3 (up to 2-fold) during warming in embryos that had been chilled for 60 min. These increases may be explained by compensation for the suppression observed during chilling and/or to activate repair mechanisms or maintain homeostasis.

Spectrophotometric Determination of Poorly Water Soluble Drug Rosiglitazone Using Hydrotropic Solubilization technique.

In the present investigation, hydrotropic solution of urea was employed as a solubilizing agent for spectrophotometric determination of poorly water-soluble drug rosiglitazone maleate. In solubility determination study, it was found that there was more than 14-folds enhancement in solubility of rosiglitazone maleate in a 6M solution of urea. Rosiglitazone maleate obeys Beer's law in concentration range of 5-300 µg/ml. Linearity of rosiglitazone maleate was found in the range of 80-120% of the label claim. The proposed method has been applied successfully to the analysis of the cited drug in pharmaceutical formulations with good accuracy and precision. The method herein described is new, simple, eco-friendly, economic, and accurate and can be utilized in routine analysis of rosiglitazone maleate in bulk drug and tablet dosage form.

Ameliorative effect of curcumin on hepatotoxicity induced by chloroquine phosphate.

India is one of the most endemic areas, where malaria predominates and its control has become a formidable task. Chloroquine phosphate (CQ) on account of its rapid action on blood schizontocide of all the malarial parasite strains has become the most widely prescribed drug for prophylaxis and treatment of malaria. Toxicity of CQ is most commonly encountered at therapeutic and higher doses of treatment. Thus, the present study was undertaken to evaluate the protective effect of Curcumin, a herbal antioxidant obtained from Curcuma longa, on hepatic biochemical and histopathological status of CQ induced male mice. Swiss albino male mice were administered oral doses of CQ (100mg/kg body wt., 200mg/kg body wt. and 300mg/kg body wt.) and CQ+curcumin (300mg/kg body wt.+80mg/kg body wt.) for 45 days. A withdrawal of high dose treatment for 45 days was also studied. Administration of CQ brought about a significant decrease in Protein content with a decline in SDH, ATPase and ALKase activities, whereas ACPase activity was found to be significantly increased following CQ treatment. Antioxidant enzyme SOD registered a significant reduction as opposed to TBARS which was found to be elevated in a significant manner in the CQ treated groups as compared to control. Gravimetric indices (body weight and organ weight) declined significantly following CQ treatment. Administration of curcumin exhibited significant reversal of CQ induced toxicity in hepatic tissue. Protein content, SDH, ATPase, ALKase, ACPase, SOD, TBARS, body weight and organ weight were found to be comparable to that of control group after curcumin administration. Thus, obtained results led us to conclude the curative potential of curcumin against CQ induced hepatotoxicity.

Management of gastroentero-pancreatic neuroendocrine tumors (GEP-NETs).

Neuroendocrine tumors (NETs) are relatively rare neoplasms that often present as diagnostic dilemmas due to obscure or non-specific symptoms. The ability of carcinoid tumors to cause clinical symptoms by secretion of hormones or biogenic amines is best recognised in the form of the carcinoid syndrome. Although generally slow growing, a significant minority demonstrate aggressive tumor growth. Ten-twenty percent of pancreatic NETs may be associated with hereditary disorders such as multiple endocrine neoplasia-1 (MEN-1) and less frequently, Von Hippel Lindau, which should be considered in the investigation and management of these patients. A small percentage of NETs are associated with co-existing synchronous non-carcinoid neoplasm. The aim of this paper was to review the optimal management in patients with NETs. The therapeutic options which are reviewed, including the use of somatostatin analogues, the role of surgery, the use of chemotherapy, biotherapy using interferon, peptide receptor targeted therapy. In addition, the challenging interventional management of liver metastases is discussed, including the role of hepatic-artery embolization, radiofrequency ablation and the place of orthotoptic liver transplantation in selected patients. Authors have focused on the newest therapeutic modalities, e.g., radionuclide peptide receptor targeted therapy with Yttrium-90 and Lutetium-177, the newest somatostatin analogues such as pasireotide and angiogenic inhibitors. In conclusion, with the increasing number of investigative procedures and therapeutic options available to diagnose and treat carcinoid tumors, it is vital to have a multidisciplinary approach. Furthermore, additional scientific research and controlled clinical trials are needed to determine the efficacy of the many treatment options, which for these rare tumors can only be achieved by collaboration.

An audit of urology two-week wait referrals in a large teaching hospital in England.

INTRODUCTION: Two week wait referral guidelines have been published by the UK Department of Health for suspected urological cancers. Concordance to these guidelines is variable. Our objectives were to assess the incidence of urological malignancy and the proportion of inappropriate referrals in the two-week wait pathway. PATIENTS AND METHODS: Retrospective audit of all two-week wait referrals to the urology department over 6 months. Inappropriate referrals were those not satisfying the referral criteria, but referred under the two-week wait system. Detection rates were calculated for each referral criterion based on diagnosis obtained from histology, imaging reports and clinic letters. RESULTS: Incidence of cancer was 90 of 400 two-week wait referrals (23%). The cancer-detection rate based on reasons for referral ranged from 50 of 122 (41%) for elevated prostate-specific antigen levels to 2 of 56 (4%) for scrotal lumps; 42 (11%) referrals were inappropriate. CONCLUSIONS: The overall cancer-detection rate is acceptable. Most inappropriate referrals were for long-standing symptoms and non-specific testicular/scrotal symptoms. The testicular cancer detection rate raises questions about the two-week wait guidelines. Providing general practitioners with fast-track scrotal ultrasound and revising the guideline may reduce the disproportionately high number of patients referred with suspected testicular cancer. Other inappropriate referrals are a cause for concern as they add to the workload of the 'urgent-referral' pathway.