Objective Clinical Improvement Research Articles

Efficacy of antimalarials in oral lichen planus: A systematic review.

To evaluate whether hydroxychloroquine (HCQ) or chloroquine (CQ) are effective for the treatment of oral lichen planus (OLP). A literature search was conducted in four databases. Clinical studies investigating the effect of HCQ/CQ in patients with OLP were included. Eleven studies were included. Four were RCTs and seven quasi-experimental studies. The studies included 390 patients diagnosed with OLP, of which 326 and 7 received HCQ and CQ, respectively. 46 patients received topical dexamethasone, 5 placebo and 6 griseofulvin as controls. Five studies assessed pain, and all of them obtained pain reduction with the use of HCQ. Six studies reported objective clinical improvement of OLP with the use of HCQ. Five studies that used a subjective scale obtained that 24%-100% of the patients achieved a complete/almost complete improvement of OLP lesions and its symptomatology. The most frequent side effects were vision problems, gastric discomfort, rash, nauseas, headaches, skin pigmentation, and elevated kidney function. 17 patients had to withdraw from the studies. Current evidence is scarce to confirm HCQ as a therapeutic option for OLP. More RCTs are needed to compare its efficacy with topical corticosteroids and to evaluate whether HCQ reduces relapses of OLP.

Bridging the Gap: Local Field Potentials Offer a Peek Into the Brain of a Person With Parkinson Disease.

Clinically available deep brain recordings in patients with Parkinson disease (PD) offer insights into disease mechanisms and create a pathway for personalized treatment strategies. This case illustrates the transformative potential of recordings of neuronal firing in the form of local field potentials (LFPs) by detailing a patient's clinical trajectory for 6 months after deep brain stimulation (DBS) surgery to treat their PD symptoms. LFPs, obtained easily in clinic with a tablet interface to measure and track brain rhythms across the disease course, enriched the patient's clinical picture. Specifically, strong beta peaks were captured at initial programming, and, as the beta peaks diminished over the course of optimizing settings, symptoms improved. These signals may also reveal insights into the neural dynamics of PD such as hypersynchrony in basal ganglia circuitry. Furthermore, the ability to record chronically may unlock new understanding of neuronal dysfunction in PD, possibly enabling future adaptive DBS. In conclusion, identification, tracking, and modulation of LFPs correlated with subjective and objective clinical improvement in the case presented. The use of neurophysiologic signals in the future may lead to therapeutic innovations for our patients with PD.

Gait Assessment in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Background and Aims. Gait impairment is a common manifestation of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, clinicians lack an effective monitoring tool, as no gait test has been validated for CIDP. The aim of this study was to determine the usefulness of three tests in monitoring the clinical course of patients with CIDP: Timed Up and Go (TUG), 10-Meter Walk Test (10MWT), and 30-Second Chair Stand (30SCS). Methods. This is a prospective, single-center observational study. We included newly diagnosed CIDP patients starting treatment or relapsed CIDP patients requiring new treatment. We monitored the clinical course using CIDP-validated clinical scales and correlated changes in clinical status with the results of the gait tests. A ROC curve was developed, and we chose the cut-off point on each scale with the best specificity and sensitivity to detect change in clinical status. Results. A total of 20 patients have been recruited. The 3 tests show a statistical correlation with objective clinical improvement. In patients who have showed clinical improvement during the follow-up examination, a mean reduction of 4.8 seconds in TUG and 2.6 in 10MWT and a gain of 3 repetitions in 30SCS have been observed. The optimal cut-off points for each test were TUG≤1 seconds, 10MWT≤1 seconds, and 30SCS≥1 repetition. The TUG test has the highest sensitivity (82.6%), and the 30SCS test has the highest specificity (100%) for detecting clinical improvement. Conclusions. The study found that the TUG and 30SCS tests could become effective tools for monitoring treatment response in CIDP patients.

Long Term Survival of Heritable Pulmonary Arterial Hypertension Associated with Hereditary Hemorrhagic Telangiectasia: A Case Series.

Hereditary hemorrhagic telangiectasia (HHT) is a hereditary disease characterized by recurrent epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations. Multiple genetic mutations have been linked to this rare disease, including ENG, ALK1 (ACVRL1), and MADH4. Pulmonary hypertension is a potential complication of HHT, with the most common phenotypes being World Health Organization (WHO) group 1 heritable pulmonary arterial hypertension (PAH), which is typically associated with ALK1 mutation; WHO group 2 pulmonary hypertension due to high output heart failure from hepatic arteriovenous malformations and/or anemia; and WHO group 2 due to high pulmonary artery wedge pressure. There is scarce evidence to help guide treatment of heritable PAH in HHT, and observational literature suggests that patients with HHT and heritable PAH have a worse prognosis compared to patients with idiopathic PAH. We describe the diagnosis, pulmonary hemodynamics, and detailed treatment courses of three patients with ALK1-associated HHT and PAH, who all exhibited objective clinical improvement with parenteral prostacyclins and oral agents.

Progressive multifocal leukoencephalopathy secondary to idiopathic CD4 lymphocytopenia treated with pembrolizumab

BackgroundProgressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease due to a lytic infection of oligodendrocytes caused by John Cunningham polyoma virus (JCV) infection. Idiopathic CD4+ T-cell lymphocytopenia (ICL) is a very rare cause of PML. MethodsWe present an individual with PML secondary to ICL treated with 3 doses of pembrolizumab, a Programmed-Death-1 Immune Checkpoint Inhibitor following with complete resolution of symptoms and conduct a review of the literature. ConclusionThis report illustrates the objective clinical and radiological improvement in a patient with PML due to ICL and suggests further study of immune checkpoint inhibitors as potential treatment for patients with PML.

Targeted therapy for <i>МЕТ</i>-positive non-small cell lung cancer

Opportunities in the treatment of patients with metastatic non-small cell lung cancer (NSCLC) are expanding every year. New targets are em erging for molecular-directed antitumor therapy, the so-called targeted therapy. One of such promising targets is damage to the MET gene. Taking into account the large number of active targets in NSCLC, the time factor and the limited amount of tumor material, conducting extensive genomic testing using NGS is preferable to routine diagnostic methods.Mutation in the form of omission of the 14 exon of MET (METex14) occurs with a frequency of 3–4%, amplification of the MET gene – in 2–4% of cases. There is evidence that these disorders correlate with a poor prognosis. At the same time, the METex14 mutation and a high level of copyness are potential predictor markers for the response to capmatinib. For molecular genetic testing, the next-generation sequencing method is optimal, which makes it possible to detect multiple, including rare disorders. Capmatinib is a low molecular weight selective reversible MET inhibitor. In preclinical studies, the drug proved effective against various types of activation of the MET signaling pathway. Clinical studies have confirmed its high antitumor activity. In the GEOMETRY mono1 study, the objective response (OR) in patients with the METex14 mutation as the first line was among 68%, in pretreated patients – 41%, with a median response duration of 12.6 months and 9.7 months, respectively. The drug demonstrated high intracranial activity, regardless of whether radiation therapy was previously performed or not. Objective antitumor response and clinical improvement to targeted therapy with capmatinib are realized fairly quickly. The results obtained during the clinical trial were reproduced in routine practice. The drug has an acceptable toxicity profile. Capmatinib is the first and so far the only drug in the Russian Federation approved for the treatment of patients with a mutation of the MET gene.

Atelocollagen-associated autologous chondrocyte implantation for the repair of large cartilage defects of the knee: Results at three to seven years

BackgroundRecently, various types of engineered autologous chondrocyte implantation (ACI) have been developed. Atelocollagen-associated ACI (A-ACI) is the only ACI procedure covered by Japanese Health Insurance since 2013. The indications of the A-ACI are traumatic cartilage defects and osteochondral dissecans (OCD) for knee joints. PurposeTo evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee. MethodsThirteen consecutive patients who underwent A-ACI between 2014 and 2018 had been prospectively enrolled in this study. There were 11 men and 2 women with a mean age of 34 years at the time of surgery. The causes of the cartilage defect were trauma in 10 knees and OCD in 3 knees. The total number of lesions was 15, which were comprised of the medial femoral condyle in 5 knees, the lateral femoral condyle in 5 knees, and the femoral trochlea in 5 knees. The mean size of the lesion was 5.3 cm2. Each knee was clinically and radiologically evaluated preoperatively and postoperatively. ResultsThe mean Lysholm score improved significantly from 74.0 points to 94.0 points (p = 0.008) and each subscale in Knee injury and Osteoarthritis Outcome Score improved significantly (p < 0.001) at the mean final follow-up period of 51 months (range, 36–84 months). The magnetic resonance observation of cartilage repair tissue 2.0 score at the mean follow-up of 38 months was significantly higher than that at 2 months postoperatively (p = 0.014). According to the International Cartilage Repair Society (ICRS) grading scale, 3 knees were graded as normal, 3 knees as nearly normal, and 1 knee as severely abnormal in second-look arthroscopic evaluation at a mean of 22 months (range, 8–41 months) after A-ACI. ConclusionThe present study showed a significant subjective and objective clinical improvement in the A-ACI for large cartilage defects of the knee at a mean follow-up of 51 months (range, 36–84 months).

Real-World Experience of Patients with Sickle Cell Disease Treated with Crizanlizumab: A Single Comprehensive Sickle Cell Center Retrospective Cohort Analysis

Background:Sickle cell disease (SCD) is an inheritable hemoglobinopathy with great impact on patients’ quality of life and healthcare costs. In 2019, crizanlizumab, the first-in-class monoclonal antibody that target the cell adhesion molecule P-selectin, was approved by the FDA to reduce the rate of vaso-occlusive crisis in patients with SCD ≥16 years old, based on the results of the SUSTAIN trial [1]. Aim: To study the real-world effectiveness of crizanlizumab in patients with SCD ≥16 years old treated with crizanlizumab 5.0 mg/kg, with or without hydroxyurea, from 2019 to 2022 in our comprehensive sickle cell center. Methods: This is a retrospective cohort analysis of patients with SCD (all genotyped, ≥16 years old) who received at least 2 consecutive doses of crizanlizumab. Demographics and laboratory findings before and after crizanlizumab were collected and analyzed. Only data available from patients’ electronic medical records (and other secondary data sources) 1 year before (pre-index data) and after (post-index data) the ≥2 consecutive crizanlizumab doses were analyzed. Objective clinical improvement was captured using the Patients’ Global Impression of Change (PGIC) score. Descriptive statistics are presented in percentages, medians, and interquartile ranges. An independent group unpaired Student's t-test was used to determine, where appropriate, the level of significant differences among normal distribution continuous variable with p value <0.05 considered statistically significant. Data was analyzed using GraphPad Prism version 9.0.2. Results:As of July 2022, there were 18 patients eligible for analysis. The median age of patients was 30.5 (range, 19-47) years, 7 (38%) males and 11 (61%) females (Table 1). Eight patients had the HbSS genotype, 7 HbSC, and 3 HbSB null. The median duration of exposure to crizanlizumab was 53.6 weeks, and 16 (89%) patients received crizanlizumab for ≥26 weeks. Crizanlizumab is very well tolerated with no serious adverse events (grade ≥3) related to treatment reported. The most commonly reported adverse events were fatigue (n=3), followed by headache (n=2) and nausea (n=2). There was no significant difference in laboratory parameters (hemoglobin, hematocrit, total bilirubin, creatinine, or protein/creatinine ratio) between pre-index and post-index values (Table 2). Although there was improvement in reticulocytes (6.5% vs. 5.1%) and LDH (336.5 vs. 279 U/L) compared with baseline, this was not statistically significant, likely due to the small sample size (p=0.71 and p=0.98, respectively). There was a remarkable improvement in patients’ subjective response with crizanlizumab infusion. The median PGIC score of our patients was 5, signifying moderately better with noticeable changes, although slight. Twelve (67%) patients provided a score of ≥4, which signifies feeling better with changes. Conclusions: This is one of the first retrospective studies to use PGIC to capture the effectiveness of crizanlizumab in patients with SCD. This study shows that crizanlizumab was associated with an improvement in patient response that was directly and indirectly related to the reduction of vaso-occlusive crisis, consistent with findings from the SUSTAIN trial. Further large-scale studies are needed to corroborate these findings.

Bacteriophage-antibiotic combination therapy against extensively drug-resistant Pseudomonas aeruginosa infection to allow liver transplantation in a toddler

Post-operative bacterial infections are a leading cause of mortality and morbidity after ongoing liver transplantation. Bacteria causing these infections in the hospital setting can exhibit high degrees of resistance to multiple types of antibiotics, which leads to major therapeutic hurdles. Alternate ways of treating these antibiotic-resistant infections are thus urgently needed. Phage therapy is one of them and consists in using selected bacteriophage viruses – viruses who specifically prey on bacteria, naturally found in various environmental samples – as bactericidal agents in replacement or in combination with antibiotics. The use of phage therapy raises various research questions to further characterize what determines therapeutic success or failure. In this work, we report the story of a toddler who suffered from extensively drug-resistant Pseudomonas aeruginosa sepsis after liver transplantation. He was treated by a bacteriophage-antibiotic intravenous combination therapy for 86 days. This salvage therapy was well tolerated, without antibody-mediated phage neutralization. It was associated with objective clinical and microbiological improvement, eventually allowing for liver retransplantation and complete resolution of all infections. Clear in vitro phage-antibiotic synergies were observed. The occurrence of bacterial phage resistance did not result in therapeutic failure, possibly due to phage-induced virulence tradeoffs, which we investigated in different experimental models.

Aggressive Central Giant Cell Granuloma of the Jaw and Adjuvant Denosumab Therapy: Decreased Morbidity and Preserved Function in a 3 Patient Case Series

We show the benefits of denosumab as adjuvant treatment of gnathic central giant cell granulomas (CGCGs) in 3 female patients, ages 18 to 65. This case series contributes to the growing experience in the medical therapy of these aggressive lesions, and demonstrates denosumab’s potential to decrease surgical morbidity. Central giant cell lesions of the jaw can be locally aggressive and thereby result in severe tissue destruction. Several medications have been evaluated as adjuvant therapy for CGCGs, with investigation of denosumab being the most recent. Our goal was to definitively treat patients with large CGCGs while minimizing unnecessary tissue and function loss. All 3 patients were offered adjuvant therapy with denosumab, since surgical resection alone would have resulted in large segmental defects requiring jaw reconstruction with free tissue transfer. Treatment instead consisted of lesion curettage and adjuvant denosumab therapy. The denosumab treatment protocol we used was based on what is currently recommended for unresectable giant cell tumors of bone (GCTB). Patients have been monitored for 40 months with clinical and radiographic exams, and 2 of them have also had histological evaluation following initiation of denosumab treatment. The 3 patients improved subjectively after the first few denosumab injections and had objective clinical and radiographic improvement after less than 6 months of therapy. Medication treatment length ranged from 10 to 15 months. Radiographic exams showed cortical thickening, resolution of cortical perforations, and calcification within a previously radiolucent region. Our findings are consistent with previous reports, and further support for the use of denosumab in locally aggressive central giant cell lesions. Our patients have thus far avoided large segmental resections, temporomandibular joint disarticulation, and sensory loss which would have resulted from surgical treatment alone. These 3 cases show that denosumab can be effective as adjuvant therapy in the treatment of aggressive gnathic CGCGs.

Surgical Outcomes in Rare Movement Disorders: A Report of Seventeen Patients from India and Review of Literature.

Background:Rare movement disorders (RMDs) throw remarkable challenges to their appropriate management particularly when they are medically refractory. We studied the outcome of functional neurosurgery among patients with RMDs.Methods:Retrospective chart-review from 2006 to 2021 of patients with RMDs who underwent either Deep brain Stimulation (DBS) or lesional surgeries in the department of Neurology and Neurosurgery at a tertiary care centre.Results:Seventeen patients were included. Generalized dystonia (11 patients, 64.7%) and tremor (5 patients, 29.4%) were the most common indication for surgery whereas, Wilson’s disease (8 patients, 47.1%) and Neurodegeneration with brain iron accumulation (5 patients, 29.4%) were the most common aetiology. Sixteen patients (94.1%) had objective clinical improvement. Significant improvement was noted in the dystonia motor scores both at 6-months and 12-months follow-up (n = 11, p-value of <0.01 and 0.01 respectively). Comparison between DBS and lesional surgery showed no significant difference in the outcomes (p = 0.95 at 6-months and p = 0.53 at 12-months), with slight worsening of scores in the DBS arm at 12-months. Among five patients of refractory tremor with Wilson’s disease, there was remarkable improvement in the tremor scores by 85.0 ± 7.8% at the last follow-up. Speech impairment was the main complication observed with most of the other adverse events either transient or reversible.Discussion:Surgical options should be contemplated among patients with disabling medically refractory RMDs irrespective of the aetiology. Key to success lies in appropriate patient selection. In situations when DBS is not feasible, lesional surgeries can offer an excellent alternative with comparable efficacy and safety.

Characterization of Crural Repair in Antireflux Surgery: Preliminary Experience with a Standardized Technique

Purpose: To define and optimize cruroplasty in laparoscopic repair of hiatal hernia (LRHH). Background: Crural closure and crural repair in LRHH are used interchangeably. While crural closure entails obliteration of the diaphragmatic defect, cruroplasty involves restoring the anatomy and producing a “functional closure.” Methods: This is an IRB-approved retrospective study. Inclusion criteria were sliding hiatal hernia ≤6 cm in axial length, abnormal pH study or erosive esophagitis, use of the endostitch device to standardize surgical bite, and endoscopic fundoplication to standardize the wrap. Exclusion criteria were a history of antireflux surgery, gastroparesis, or preexisting esophageal stricture. Results: A total of 68 patients, 21 males, and 47 females met the inclusion criteria. The median age and BMI were 59 and 28, respectively. The average follow-up was 26.3 (12–62) months. There were three anatomical recurrences 3/68 (4.4%) and two of them had symptomatic recurrence. All but eight patients discontinued antisecretory therapy 60/68 (88.2%). Five of these eight patients used these medications at lesser dose or frequency rendering the overall improvement of patients to 65/68 (95.5%). There was no postoperative dysphagia. Conclusions: Laparoscopic hiatal hernia repair should focus on crural repair, not merely closure. Optimizing cruroplasty can be achieved by understanding the functional anatomy, recreating the crural sling, and adjusting the crural suture tension. This results in a low recurrence rate of hiatal hernias, a high discontinuation rate of proton pump inhibitors, significant objective clinical improvement of GERD symptoms, and no postoperative dysphagia.

Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae

A 30-year-old bombing victim with a fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term (>700 days) antibiotic therapy is treated with a pre-adapted bacteriophage along with meropenem and colistin, followed by ceftazidime/avibactam. This salvage therapy results in objective clinical, microbiological and radiological improvement of the patient’s wounds and overall condition. In support, the bacteriophage and antibiotic combination is highly effective against the patient’s K. pneumoniae strain in vitro, in 7-day mature biofilms and in suspensions.

Do we really listen?

IntroductionThe improvement perceived by the patients is a subjective measure of the psychic state, while the clinical evaluation corresponds to an objective evaluation of the psychopathological improvement performed by a psychiatrist. It is therefore relevant to evaluate whether these parameters evolve in a common way after patients have undergone an intervention in Day Hospital focusing on first psychotic episodes.ObjectivesStudy the relationship between subjective improvement and clinical evaluation.MethodsThis is a prospective study, which includes consecutive patients admitted to the Day Hospital during 2018. Their objective clinical improvement was assessed by means of the PANSS and GAF scales at admission and discharge. Subjective clinical improvement was assessed using an anonymous Likert scale with a score between 1 and 7. Sociodemographic data and other satisfaction parameters were also collected. A statistical analysis was performed using Pearson’s correlation.ResultsA total of 73 patients were included. The perception of improvement on the part of the patients is very high presenting average values close to the maximum in almost all the evaluated items. The correlation between subjective improvement and PANSS variation presented a Pearson value 0.008; p = .957 and with the GAF variation presented a Pearson correlation of -0.066; p = .578 which indicates that there is no significant correlation between the variables.Diagnostic groupsFrequencyPercentageDrugs11,4Psychosis3750.7Affective2128.8Neurosis1013.7Personality34.1Total72ConclusionsClinical evaluation and subjective perception of improvement are independent parameters.

A pilot clinical trial of oral tetrahydrouridine/decitabine for noncytotoxic epigenetic therapy of chemoresistant lymphoid malignancies

One mechanism by which lymphoid malignancies resist standard apoptosis-intending (cytotoxic) treatments is genetic attenuation of the p53/p16-CDKN2A apoptosis axis. Depletion of the epigenetic protein DNA methyltransferase 1 (DNMT1) using the deoxycytidine analog decitabine is a validated approach to cytoreduce malignancy independent of p53/p16. In vivo decitabine activity, however, is restricted by rapid catabolism by cytidine deaminase (CDA). We, therefore, combined decitabine with the CDA-inhibitor tetrahydrouridine and conducted a pilot clinical trial in patients with relapsed lymphoid malignancies: the doses of tetrahydrouridine/decitabine used (∼10/0.2 mg/kg orally (PO) 2×/week) were selected for the molecular pharmacodynamic objective of non-cytotoxic, S-phase dependent, DNMT1-depletion, guided by previous Phase 1 studies. Patients with relapsed/refractory B- or T-cell malignancies (n = 7) were treated for up to 18 weeks. Neutropenia without concurrent thrombocytopenia is an expected toxicity of DNMT1-depletion and occurred in all patients (Grade 3/4). Subjective and objective clinical improvements occurred in 4 of 7 patients, but these responses were lost upon treatment interruptions and reductions to manage neutropenia. We thus performed parallel experiments in a preclinical in vivo model of lymphoma to identify regimen refinements that might sustain DNMT1-targeting in malignant cells but limit neutropenia. We found that timed-alternation of decitabine with the related molecule 5-azacytidine, and combination with inhibitors of CDA and de novo pyrimidine synthesis could leverage feedback responses of pyrimidine metabolism to substantially increase lymphoma cytoreduction but with less neutropenia. In sum, regimen innovations beyond incorporation of a CDA-inhibitor are needed to sustain decitabine DNMT1-targeting and efficacy against chemo-resistant lymphoid malignancy. Such potential solutions were explored in preclinical in vivo studies.

EXTH-77. ONC201 EXHIBITS PASSIVE DIFFUSION AND BROAD DISTRIBUTION IN THE CENTRAL NERVOUS SYSTEM

Abstract Imipridone ONC201 is an investigational agent in phase II clinical trials for H3 K27M-mutant diffuse midline glioma with evidence of durable objective responses and clinical symptom improvements as a single agent. The systemic pharmacokinetics of ONC201 and its ability to achieve target concentrations in supratentorial glioblastoma have been demonstrated in clinical trials; however, its clearance and distribution in midline structures and other areas of the central nervous system (CNS) haven’t been evaluated. A quantitative whole-body autoradiography study was conducted in Long-Evans rats with a single dose of [14C]-ONC201. [14C]-ONC201-related material was rapidly distributed throughout the body, with concentrations peaking at 1h for most tissues. The endocrine, metabolic/excretory, ocular and gastrointestinal tract tissues contained the highest distribution of [14C]-ONC201-derived radioactivity. Importantly, [14C]-ONC201 material was distributed evenly across brain substructures, including the meninges and midline structures of the brain; all tissues had a half-life of 1.4–7.9h, with the exception of the meninges (2397.3h). Given the uniform distribution throughout the CNS, we evaluated the permeability and efflux potential of ONC201 in bidirectional transport assays using human Caco-2 cell monolayers. ONC201 displayed high permeability in the apical to basolateral direction with apparent permeability values of 23–31×10–6 cm/s at 7–700μM. In the basolateral to apical direction, apparent permeability values were 11–24 × 10–6 cm/s. The efflux ratio values were 0.46–0.79 for ONC201, suggesting that ONC201 is not a substrate of efflux transporters. However, ONC201 exerted inhibitory potential on MDR1- (90.6%) and BCRP-mediated (81.6%) transport at 200mM. In summary, ONC201 exhibits passive diffusion without being effluxed, which may enable its rapid and wide distribution throughout the CNS. This distribution profile suggests that the compound may achieve therapeutic concentrations throughout the CNS with oral administration and that investigation of additional CNS tumors will not be hindered by drug delivery to specific anatomic structures.

Low-dose oral minoxidil as treatment for non-scarring alopecia: a systematic review.

Topical minoxidil has been used for almost 40years to treat alopecia. There is growing evidence supporting off-label use of low-dose oral minoxidil. To conduct a systematic review evaluating the use of oral minoxidil for all types of alopecia. A primary literature search was conducted using PubMed in May 2019, utilizing the search term "oral minoxidil AND (hair loss OR alopecia OR baldness)". Reviews, non-English studies, and articles concerning only topical minoxidil were excluded. Ten articles were included for review comprising a total 19,218 patients (215 women and 19,003 men). Oral minoxidil dose ranged from 0.25 to 5mg daily to twice daily. The strongest evidence existed for androgenetic alopecia and alopecia areata (AA), with 61-100% and 18-82.4% of patients demonstrating objective clinical improvement. Successful treatment of female pattern hair loss, chronic telogen effluvium, monilethrix, and permanent chemotherapy-induced alopecia was also reported. The most common adverse effects with oral minoxidil included hypertrichosis and postural hypotension. Oral minoxidil is a safe and successful treatment of androgenic alopecia and AA. In addition to its therapeutic benefits, practical advantages over topical minoxidil stem from improved patient compliance.

Robo-Cob technique; transoral endoscopic coblation tongue base resection in obstructive sleep apnea patients.

Another transoral tongue base surgical procedure for obstructive sleep apnea (OSA) is described. The procedure was named as the "Robo-Cob" technique because it is similar to transoral robotic surgery (TORS) but using a coblation technology to manage tongue base hypertrophy in patients with OSA especially in countries where TORS is not an available option for such benign conditions. The technique is described step by step. The new surgical technique was carried out in 25 adult OSA patients with mean age of 41.36 ± 8.72years (average 23-56) with confirmed tongue base hypertrophy by preoperative drug-induced sleep endoscopy (DISE). Coblation was used to resect, not ablate, the tongue base with similar technique as described in TORS. The Robo-Cob technique is proved to be feasible and effective in all cases either alone or when combined with other procedures in multilevel surgery settings. There were no significant intraoperative or postoperative complications. No tracheostomy was done in any patient. Objective clinical improvement was confirmed by polysomnography 3months postoperatively with significant decrease in mean AHI from 33.84 ± 10.54 to 11.52 ± 5.42 (P< 0.005). Moreover, this technique provided tongue base tissue specimen that allowed measurement of its volume that ranged from 10 to 22cc (mean 14.96 ± 3.62cc) to monitor extent of tissue resection. The added value of using coblation in resection, not ablation, is being quicker, and being able to provide tissue specimen to measure its volume to judge resection limits.

Transoral Endoscopic Coblation Tongue Base Surgery in Obstructive Sleep Apnea: Resection versus Ablation

Background: A new transoral tongue base surgical procedure for the treatment of snoring and obstructive sleep apnea (OSA) is described. It is named “Robo-Cob” technique because it is similar to transoral robotic surgery (TORS) but it is performed by means of coblation technology in order to resect the tongue base in countries where TORS is not an available option for such benign conditions. Methods: In this prospective, randomized, controlled trial, the new Robo-Cob technique was carried out in 25 adult OSA patients with confirmed tongue base hypertrophy at preoperative drug-induced sedation endoscopy. The results of this procedure were compared with the coblation endoscopic lingual lightening (CELL) technique used to ablate (or minimally resect) the central part of the tongue base, in another 25 adult OSA patients with similar characteristics (age, sex, preoperative body mass index and Apnea-Hypopnea Index, AHI). The base of tongue surgery was part of multilevel surgery including also septoturbinoplasty and barbed reposition pharyngoplasty (with/without tonsillectomy). Results: In this study, the Robo-Cob technique is proved to be feasible and effective in all cases either alone or when combined with other procedures in multilevel surgical settings. No/minimal intraoperative or postoperative complications were observed. Postoperative pain as measured by visual analog scale ranged from 3 to 7. No tracheostomy was done in any patient. Objective clinical improvement was confirmed by a level 3 polygraphy performed 6 months after surgery. There was significant difference in operative time at the level of the tongue base between Robo-Cob and CELL techniques, with shorter times observed within the Robo-Cob group. Moreover, the Robo-Cob technique provided tongue base tissue specimens that allowed measurement of the volume that ranged from 5 to 17 cm³ (mean 11.64 ± 3.49 cm³). It was found that resection of at least 10 cm³ of tongue base tissue was associated with better outcomes in terms of postoperative AHI reduction. Conclusion: In this study, the added values of using coblation for resection and not ablation appear to be the short surgical time, the low postoperative tissue edema, and the possibility of providing tissue specimens to measure resected volumes.

Sarcoid-like granulomatous orbitopathy-presentation, systemic involvement and clinical outcome.

To describe patients with sarcoid-like granulomatous orbitopathy (SLGO), the rate of known and subsequent systemic sarcoidosis, and the treatment and outcome for the condition. Retrospective review of patients with SLGO presenting between 1990 and 2018, excluding solely lid or lacrimal drainage disease. Sixty-one patients (45 female; 74%) were identified, 54 having biopsy-proven sarcoidosis (47 orbital, 24 prior extra-orbital), and half were Afro-Caribbean. The average age at presentation was 45.3 years (range 18-78 years), with the commonest symptoms being swelling, pain and diplopia; of clinical signs, most patients (87%) had eyelid swelling, reduced motility (25%), and disease-related visual impairment (10%). Localized dacryoadenitis was present in 49/61 (21/49 bilateral) patients, and more diffuse disease in 28/61 (8/28 bilateral). Systemic involvement was found in 23 (62%) of the 37 first presenting with orbital disease. Twenty-three (38%) patients were observed and two-thirds received oral corticosteroids, with 53/61 (87%) patients having subjective and objective clinical improvement. The average follow-up was 53.4 months (range 1-315 months) and clinical recurrence occurred in 12 (20%) patients at 26.5 months (range 1-115 months) after first diagnosis. Systemic sarcoidosis may be discovered in about two-thirds of patients presenting with SLGO (that tends to present with inflammatory features), but the treatment response appears similar in patients with known sarcoidosis and those with newly-diagnosed systemic disease after orbital presentation. With long-term follow-up, a third of patients have spontaneous regression of orbital disease, but 20% have recurrence after reducing or stopping systemic immunosuppression.