Black Turmeric and Aloe Vera in the Management of Oral Submucous Fibrosis: A Prospective Clinical Study.

AIM: To determine the therapeutic efficacy of Kali haldi in the management of Oral submucous Fibrosis (OSMF) v/s steroid therapy. MATERIALS AND METHODS: A clinical prospective study was conducted on 42 patients of oral submucous fibrosis were equally divided into 2 groups. Group A patients were treated with a mixture of powdered Kali Haldi and aloe vera gel in equal ratio 3 times a day for 3 months. Group B patients were treated with intralesional injection of hydrocortisone and hyaluronidase for 6 weeks with oral antioxidant supplements for 3 months. Burning sensation, cheek flexibility, mouth opening, and tongue protrusion were evaluated before, during, and after treatment at an interval of 15 days, 1 month, 2, month and 3 months. RESULTS: Statistically significant results were obtained at the end of 3 months duration for both the groups (P < 0.001). The Symptomatic correction was more evident in the case of Group A patients than Group B. Response of the ayurvedic regimen was potentially better as compared to the regular steroid therapy. CONCLUSION: The study concludes that Combination therapy works wonders in the case of OSMF in stages I, II, III and can be a good option, comparatively safe and with negligible side effects, but potent and equally effective management of oral submucous fibrosis. Henceforth, it will be better to do such kinds of studies on a vast scale including larger samples and longer duration to check the efficacy and durability of this ancient ayurvedic regimen.

Roles of glomerular endothelial hyaluronan in the development of proteinuria.

Vascular endothelial cells are covered with glycocalyx comprising heparan sulfate, hyaluronan, chondroitin sulfate, and associated proteins. Glomerular endothelial glycocalyx is involved in protecting against induction of proteinuria and structural damage, but the specific components in glycocalyx that represent therapeutic targets remain unclear. Anti-vascular endothelial growth factor (VEGF) therapy is associated with an increased risk of glomerular endothelial injury. This study investigated whether hyaluronan could provide a therapeutic target to protect against proteinuria. We conducted ex vivo and in vivo experiments to explore the effects of degrading glomerular hyaluronan by administering hyaluronidase and of supplementation with hyaluronan. We investigated hyaluronan expression using biotin-labeled hyaluronan-binding protein (HABP) in human kidney specimens or serum hyaluronan in endothelial injuries under inhibition of VEGF signaling. We directly demonstrated hyaluronan in glomerular endothelial layers using HABP staining. Ex vivo and in vivo experiments showed the development of proteinuria after digestion of hyaluronan in glomerular capillaries. Supplementation with hyaluronan after hyaluronidase treatment suppressed proteinuria. Mice in the in vivo study developed albuminuria after intraperitoneal injection of hyaluronidase with decreased glomerular hyaluronan and increased serum hyaluronan. In human kidneys with endothelial cell dysfunction and proteinuria due to inhibition of VEGF, glomerular expression of hyaluronan was reduced even in normal-appearing glomeruli. Serum hyaluronan levels were elevated in patients with pre-eclampsia with VEGF signaling inhibition. Our data suggest that hyaluronan itself plays crucial roles in preventing proteinuria and preserving the integrity of endothelial cells. Hyaluronan could provide a therapeutic target for preventing glomerular endothelial glycocalyx damage, including VEGF signaling inhibition.

Transient retinal artery occlusion after phacoemulsification under local anesthetic block / Oclusão arterial retiniana transitória após facoemulsificação sob bloqueio anestésico

ABSTRACT We here in report the case of a patient subjected to cataract surgery through phacoemulsification under local anesthetic block, without intra-operative complications. The patient presented important visual impairment in the first post-operative day. Fundoscopy showed pallor resembling cherry-red spots at the macula. Fluorescein angiography did not depict signs of vascular occlusion and the spectral-domain optical coherence tomography showed increased reflectivity in the inner layers of the retina, thus suggesting local thickening and edema. The current case led to the diagnostic hypothesis of transient retinal arterial occlusion.

RESUMO Relatamos um caso de um paciente submetido a facectomia por facoemulsificação sob bloqueio anestésico peribulbar, sem intercorrências per-operatória, que apresentou no primeiro dia de pós-operatório baixa visual significativa. À fundoscopia observou-se palidez em aspecto de mácula em cereja. A angiofluoresceinografia não demonstrou sinais de oclusão vascular e a tomografia de coerência óptica mostrou aumento da refletividade das camadas internas da retina, sugerindo espessamento e edema local. No caso descrito foi aventada hipótese diagnóstica de oclusão arterial retiniana transitória.

Treatment of skin soft tissue embolism after hyaluronic acid injection for injection rhinoplasty in Asian patients.

INTRODUCTION: The purpose of this manuscript is to investigate the treatment of skin soft tissue embolization or vascular occlusion after the injection of hyaluronic acid (HA) for Injection Rhinoplasty (IR) in Asians with a special interest in the time occurrence of the occlusion. METHODS: A total of 35 cases were evaluated after receiving HA injections for IR who presented with a vascular occlusive event. They were divided into three stages based on the time to embolization. Immediate, ≤5 hours; early, ≤3 days; and late, >3 days. There were two cases of immediate, 28 deemed early, and five late. Methods to prevent tissue necrosis are reviewed in the manuscript based on these stages. RESULTS: Skin color gradually recovered to normal after 11 treatments in 11 patients with mild embolization. No ischemic aggravation or skin necrosis was observed in 19 patients with moderate embolization; red scarring was seen in two and hypertrophic scar with uneven skin color in one patient. The five patients in the severe category had longer healing, more red scars, and more hypertrophic scarring. CONCLUSION: The treatment of skin soft tissue embolization or vascular occlusion after HA IR in Asians can be effected by identifying the stage and degree of embolization and treating appropriately with the outlines presented in this manuscript.

Light Perception Vision Recovery After Treatment for Calcium Hydroxylapatite Cosmetic Filler-Induced Blindness.

A 51-year-old woman presented with no light perception vision of the right eye 12 hours after another provider injected calcium hydroxylapatite into the glabella and dorsum of the nose. Exam and fluorescein angiography demonstrated optic nerve edema and choroidal hypoperfusion consistent with ischemia of the posterior ciliary circulation. The central retinal circulation appeared intact. One thousand two hundred units of retrobulbar hyaluronidase were injected urgently in several boluses. Oral prednisone and aspirin also were administered. Ocular massage was also initiated. One day later, visual acuity improved to light perception that remained stable at 3 months. Retrobulbar hyaluronidase injection, ocular massage, prednisone, and aspirin were correlated to recovery of light perception vision in this case of calcium hydroxylapatite filler embolization to the choroidal circulation. The mechanism for the recovery of some vision and the role of hyaluronidase and other medications remain uncertain. Further research in treatments for ophthalmic complications of facial fillers is warranted.

Differentiating Nonpermanent Injectable Fillers: Prevention and Treatment of Filler Complications.

Though the incidence of complications and adverse events with dermatological fillers is inherently low, practitioners should be well versed in both prevention of filler complications and the treatment algorithms for addressing "granulomas," nodules, infection, and vascular compromise. Appropriate preventative measures, coupled with timely and effective treatment, are critically important for patient safety and satisfaction. In addition to the preventive measures and treatment algorithms outlined here, the authors emphasize that the broad classification and treatment of nodules as "granulomas" is likely to lead to ineffective treatment, or worse, unnecessary exposure to incorrect treatment. In practice, nodules are classified and treated based on clinical manifestation (eg, late vs early or noninflammatory vs inflammatory) rather than on histology. Indeed, classification of a nodule as a granuloma requires a histological examination, rarely available (or necessary) in clinical practice to guide treatment. Thus, the apparent inflammatory nature of the nodule and the time of onset should drive treatment approach. The treatment algorithms presented here are based on these clinically meaningful parameters.

Use of hyaluronidase as an adjunct to local anaesthetic eye blocks to reduce intraoperative pain in adults.

BACKGROUND: Hyaluronidase has been used over many decades as an adjunct to local anaesthetic solution to improve the speed of onset of eye blocks and to provide better akinesia and analgesia. With the evolution of modern eye surgery techniques, fast onset and akinesia are not essential requirements anymore. The assumption that the addition of hyaluronidase to local anaesthetic injections confers better analgesia for the patient needs to be examined. There has been no recent systematic review to provide evidence that hyaluronidase actually improves analgesia. OBJECTIVES: To ascertain if adding hyaluronidase to local anaesthetic solutions for use in ophthalmic anaesthesia in adults results in a reduction of perceived pain during the operation and to assess harms, participant and surgical satisfaction, and economic impact. SEARCH METHODS: We carried out systematic searches in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and four other databases in June 2017. We searched the trial registers at www.ISRCTN.com, ClinicalTrials.gov and www.clinicaltrialsregister.eu for relevant trials. We imposed no language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated the effect of hyaluronidase on pain experienced by adults during intraocular surgery using a rating scale. DATA COLLECTION AND ANALYSIS: Two review authors (HR and KA) independently extracted data and assessed methodological quality using standard procedures as expected by Cochrane. MAIN RESULTS: We included seven trials involving 500 participants that studied the effect of hyaluronidase on intraoperative pain. Four of the seven trials with 289 participants reported the primary outcome in a dichotomous manner, and we proceeded to meta-analyse the findings which showed a moderate heterogeneity that could not be explained (I2 = 41% ). The pooled risk ratio (RR) for these four trials was 0.83 with the 95% confidence interval ranging from 0.48 to 1.42. The reduction in intraoperative pain scores in the hyaluronidase group were not statistically significant. Among the three trials that reported the primary outcome in a continuous manner, the presence of missing data made it difficult to conduct a meta-analysis. To further explore the data, we imputed standard deviations for the other studies from another included RCT (Sedghipour 2012). However, this resulted in substantial heterogeneity between study estimates (I² = 76% ). The lack of reported relevant data in two of the three remaining trials made it difficult to assess the direction of effect in a clinical setting.Overall, there was no statistical difference regarding the intraoperative reduction of pain scores between the hyaluronidase and control group. All seven included trials had a low risk of bias.According to GRADE, we found the quality of evidence was low and downgraded the trials for serious risk of inconsistency and imprecision. Therefore, the results should be analysed with caution.Participant satisfaction scores were significantly higher in the hyaluronidase group in two high quality trials with 122 participants. Surgical satisfaction was also superior in two of three high quality trials involving 141 participants. According to GRADE, the quality of evidence was moderate for participant and surgical satisfaction as the trials were downgraded for imprecision due to the small sample sizes. The risk of bias in these trials was low.There was no reported harm due to the addition of hyaluronidase in any of the studies. No study reported on the cost of hyaluronidase in the context of eye surgery. AUTHORS' CONCLUSIONS: The effects of adding hyaluronidase to local anaesthetic fluid on pain outcomes in people undergoing eye surgery are uncertain due to the low quality of evidence available. A well designed RCT is required to address inconsistency and imprecision among the studies and to determine the benefit of hyaluronidase to improve analgesia during eye surgery. Participant and surgical satisfaction is higher with hyaluronidase compared to the control groups, as demonstrated in moderate quality studies. There was no harm attributed to the use of hyaluronidase in any of the studies. Considering that harm was only rarely defined as an outcome measure, and the overall small number of participants, conclusions cannot be drawn about the incidence of harmful effects of hyaluronidase. None of the studies undertook cost calculations with regards to use of hyaluronidase in local anaesthetic eye blocks.

Omega 3: a novel treatment agent in oral submucous fibrosis: a pilot study.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic debilitating disease and a premalignant condition of the oral cavity. It is well known for its impervious nature to medical therapy. Omega-3 polyunsaturated fatty acids have been reported to have anti-inflammatory properties. However, its role in OSF is still not known. This preliminary study assessed the efficacy of systemic omega 3 in this disease. METHODS: A randomized single-blinded controlled trial was designed, and a total of 10 clinically confirmed adult patients with OSF were included in the study. Group A was given biweekly intralesional injections of dexamethasone 1.5 ml and hyaluronidase 1500 IU mixed with lignocaine for 6 weeks and a placebo for 3 months. Group B was also given similar intralesional injections but with 1 gm of omega 3 three times daily continuously for 3 months. Patients were followed every month for 3 months and then after 6 months. RESULTS: Significant improvement was noted among all clinical parameters (interincisal distance, tongue protrusion, cheek flexibility, and visual analogue scale) in both the groups. Intergroup comparison showed significant reduction in burning sensation in group B; that is, P value was 0.005, while improvement in rest of the three clinical features was not statistically significant. CONCLUSION: Omega 3 can be used as an adjunctive treatment option in patients with OSF to reduce subjective symptoms. More studies should be conducted with a larger sample size to study the effect of omega 3 in patients with OSF.

Breaching the Hyaluronan Barrier with PH20-Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales.

In contrast to traditional strategies based on external driving forces, an internal path for intratumoral delivery is explored by degrading the tumor microenvironment component hyaluronan. Natural hyaluronidase PH20 and constructed long-acting PH20-Fc have been used to achieve this objective. It has been then evaluated how these agents facilitate the diffusion of the following typical therapeutic agents varying in nanoscales: doxorubicin (≈1.5 × 1.0 × 0.7 nm) chemotherapy, trastuzumab (10-15 nm) biotherapy, and gold nanorod (≈100 × 35 nm) thermotherapy. In traditional 2D cultures, PH20 and PH20-Fc have little influence on cytotoxicity due to lack of a tumor microenvironment. However, the cytotoxicities of the three therapeutic agents in 3D tumor spheroids are all enhanced by PH20 or PH20-Fc because hyaluronan degradation facilitates therapeutic penetration and accumulation. Furthermore, in vivo evaluations reveal that the significantly prolonged circulation time of PH20-Fc leads to accumulation in the tumor and subsequent hyaluronan degradation. Consequently, PH20-Fc coadministration further inhibits tumor growth. The performance of PH20-Fc varies for the three therapeutic agents due to their different nanoscales. Trastuzumab benefits most from combination with PH20-Fc. The results provide here novel insights that can aid in the development of more effective hyaluronidase-based therapeutic systems.

Comparison of Peribulbar with Posterior Sub-Tenon's Anesthesia in Cataract Surgery Among Nigerians.

PURPOSE: To compare the akinetic and the analgesic effects of peribulbar and posterior sub-Tenon's anesthesia in patients undergoing cataract surgery. METHODS: In a hospital-based randomized comparative interventional study, patients aged 50 years and above who underwent elective surgery for uncomplicated cataract were randomized to receive either peribulbar block or posterior sub-Tenon block. Pain during injection, surgery, and after surgery was assessed using numerical reporting scale (NRS). Limbal excursion was measured with a transparent meter rule. RESULT: A total of 152 eyes of 152 patients were studied. Peribulbar and sub-Tenon regional blocks provided comparable adequate akinesia (P = 0.06) and similar levels of analgesia (P = 0.10) during cataract surgery. Both techniques also provided similar levels of analgesia to the patient during injection and in the immediate postoperative period. Ninety-two percent of patients who had peribulbar and 97% of those who had sub-Tenon blocks reported either mild pain or no pain at all during surgery (P = 0.49). There was no report of severe pain in all patients during the stages of the surgery. Occurrence of chemosis and subconjunctival hemorrhage was more common in sub-Tenon than peribulbar anesthesia. CONCLUSIONS: This study shows that peribulbar and posterior sub-Tenon routes of administering anesthetic substances is comparable in providing adequate akinesia and analgesia for cataract surgery with minimal complications. Therefore, both techniques are effective and safe for cataract surgery among Nigerians.

Guidelines for the use of local anesthesia in office-based dermatologic surgery.

There are an increasing number and variety of dermatologic surgical procedures performed safely in the office setting. This evidence-based guideline addresses important clinical questions that arise regarding the use and safety of local anesthesia for dermatologic office-based procedures. In addition to recommendations for dermatologists, this guideline also takes into account patient preferences while optimizing their safety and quality of care. The clinical recommendations presented here are based on the best evidence available as well as expert opinion.

Effect of clonidine added to lidocaine for sub-Tenon's (episcleral) anesthesia in cataract surgery.

PURPOSE: We aimed to evaluate the duration of anesthesia, analgesia and ocular akinesia of clonidine added to lidocaine in sub-Tenon's anesthesia in patients undergoing cataract surgery. METHODS: Forty patients were prospectively enrolled. They were randomized to two sub-Tenon's anesthesia groups: group L (6 ml of lidocaine 2 %, 1 ml of 0.9 % saline and 25 UI/ml of hyaluronidase), and group C (6 ml lidocaine 2 %, clonidine 1 µg/kg, 1 ml of 0.9 % saline and 25 UI/ml of hyaluronidase). Duration of sensory anesthesia, ocular akinesia in all directions, akinesia of the levator palpebrae superioris and orbicularis oculi muscles, the duration of analgesia (time to the first postoperative use of analgesics), the overall use of analgesics and the presence of adverse effects were recorded . RESULTS: The duration of sensory anesthesia and akinesia of the four rectus, levator palpebrae superioris, and orbicularis oculi muscles was significantly longer in group C (p < 0.05). The number of patients who required analgesics was similar between the groups but the duration of analgesia was longer in group C (p < 0.05). No significant adverse effects were observed. CONCLUSION: The addition of clonidine 1 µg/kg to 2 % lidocaine in sub-Tenon's anesthesia for cataract surgery increased the duration of sensory anesthesia, ocular akinesia, and the duration of analgesia.

[Rehabilitation of patients with urolithiasis after minimally invasive procedures on the kidneys].

Minimally invasive surgeries in patients with urolithiasis are not always successful. Prevention of inflammatory and cicatrical-sclerotic complications in the postoperative period plays an important role. 49 patients with urolithiasis divided into two groups were followed-up. The study group included 25 patients who underwent percutaneous puncture nephrolitholapaxy. The control group consisted of 24 patients with a history of percutaneous puncture nephrolitholapaxy. In postoperative period, active prevention of inflammation and cicatrical-sclerotic complications using drug Longidaza in combination with magnetic-laser therapy was performed in study group. The control group received standard treatment. 6 months after surgery, 1 (4%) patient in the study group had pyeloectasis approximately 2 cm and obstruction of UPJ of operated kidney, which required re-treatment with Longidaza. In the control group, pyeloectasis and violation of passage through the upper urinary tract were recorded in 4 (16.7%) patients. These data allow to recommend a comprehensive prevention of postoperative inflammation and cicatrical-sclerotic complications using Longidaza and magnetic-laser therapy in patients undergoing minimally invasive surgery of the kidney.

Undesirable effects after treatment with dermal fillers.

BACKGROUND: Soft tissue augmentation is one of the most frequent techniques in cosmetic dermatology. Nowadays, there are a high number of available materials. Nonanimal hyaluronic acid (HA) is one of most useful fillers for lip augmentation and for treating nasolabial folds, marionette lines, and the dynamic wrinkles of the upper face. OBJECTIVE: To evaluate the type and management of undesirable effects of nonanimal reticulated or stabilized HA observed in our cosmetic unit in the past 3 years. MATERIALS AND METHODS: The consecutive patients using HA attending to our clinic in the past 3 years were divided into 3 categories, according to the time of presentation of the adverse reactions: immediate, early, and late-onset complications. All patients were treated. RESULTS: Twenty-three patients presented to our clinic complaining of complications after soft tissue augmentation with HA. Ten patients presented immediate-onset complications, 8 showed early-onset complications, and 5 cases complaint of late-onset complications. Treatment of the first group consisted of hyaluronidase injection, massage, and topical antibiotics. Early- and late-onset complications were treated with intralesional triamcinolone acetonide. All patients improved, with the exception of a woman with recurrent granulomas. CONCLUSION: Generally, undesirable effects of HA (immediate, early, or late onset) are not frequent, and when present, they improve if treated properly. Physicians need to be aware of these possible adverse events in order to establish proper treatment and prevent scarring or other sequelae.

Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinomas (PDAs) are characterized by a robust fibroinflammatory response. We show here that this desmoplastic reaction generates inordinately high interstitial fluid pressures (IFPs), exceeding those previously measured or theorized for solid tumors, and induces vascular collapse, while presenting substantial barriers to perfusion, diffusion, and convection of small molecule therapeutics. We identify hyaluronan, or hyaluronic acid (HA), as the primary matrix determinant of these barriers and show that systemic administration of an enzymatic agent can ablate stromal HA from autochthonous murine PDA, normalize IFP, and re-expand the microvasculature. In combination with the standard chemotherapeutic, gemcitabine, the treatment permanently remodels the tumor microenvironment and consistently achieves objective tumor responses, resulting in a near doubling of overall survival.

Staggered sub-Tenon's blocks: a novel anesthetic approach for bilateral strabismus surgery.

Bilateral strabismus surgery is usually performed under general anesthesia. However, sometimes general anesthesia is not in the best interest of patients presenting with advanced multiple comorbidities. These patients are best treated with local anesthesia instead. However, the bilateral nature of the surgery becomes an issue because bilateral akinetic needle blocks for ophthalmic surgery have not been described before. This article describes a novel approach for bilateral eye surgery in three patients who were at high risk from general anesthesia but needed to have the surgery performed in the same sitting. Staggered blunt needle sub-Tenon's blocks were chosen over sharp needle akinetic extraconal peribulbar or intraconal retrobulbar blocks on account of their predictability, relative safety, and efficacy. The potential systemic complications of bilateral injections were minimized by staggering the blocks. This technique may be an option for high-risk patients who are not candidates for general anesthesia but require bilateral ophthalmic surgery performed in a single surgical episode.

Clinical trial for safety evaluation of hyaluronidase as diffusion enhancing adjuvant for infiltration analgesia of skin with lidocaine.

BACKGROUND: Infiltration anesthesia of the skin is an analgesic procedure often practiced before minor surgical interventions or punctures. The addition of hyaluronidase is a possible option to improve the effectiveness of the local anesthetic with respect to expansion of effect. OBJECTIVE: To validate the safety of intracutaneous application of hyaluronidase as a lidocaine adjuvant. MATERIALS AND METHODS: The influence of adjuvant hyaluronidase on wound healing was investigated using the suction blister method in a prospective, single-center, placebo-controlled, double-blind, intraindividual comparison study with 20 participants. The target parameters were defined as the time of normalization of transepidermal water loss, hemovascular perfusion, and complete macroscopic epithelization of the wound. RESULTS: No evidence was found that adjuvant application of hyaluronidase retards wound healing. CONCLUSION: The addition of hyaluronidase to lidocaine in intracutaneous infiltration analgesia does not lead to retardation of wound healing, and no additional relevant risks were observed.