Enhancing teeth segmentation using multifusion deep neural net in panoramic X-ray images.

BACKGROUND: Precise teeth segmentation from dental panoramic X-ray images is an important task in dental practice. However, several issues including poor image contrast, blurring borders of teeth, presence of jaw bones and other mouth elements, makes reading and examining such images a challenging and time-consuming task for dentists. Thus, developing a precise and automated segmentation technique is required. OBJECTIVE: This study aims to develop and test a novel multi-fusion deep neural net consisting of encoder-decoder architecture for automatic and accurate teeth region segmentation from panoramic X-ray images. METHODS: The encoder has two different streams based on CNN which include the conventional CNN stream and the Atrous net stream. Next, the fusion of features from these streams is done at each stage to encode the contextual rich information of teeth. A dual-type skip connection is then added between the encoder and decoder to minimise semantic information gaps. Last, the decoder comprises deconvolutional layers for reconstructing the segmented teeth map. RESULTS: The assessment of the proposed model is performed on two different dental datasets consisting of 1,500 and 1,000 panoramic X-ray images, respectively. The new model yields accuracy of 97.0% and 97.7%, intersection over union (IoU) score of 91.1% and 90.2%, and dice coefficient score (DCS) of 92.4% and 90.7% for datasets 1 and 2, respectively. CONCLUSION: Applying the proposed model to two datasets outperforms the recent state-of-the-art deep models with a relatively smaller number of parameters and higher accuracy, which demonstrates the potential of the new model to help dentists more accurately and efficiently diagnose dental diseases in future clinical practice.

SARS-CoV-2 (COVID-19) structural and evolutionary dynamicome: Insights into functional evolution and human genomics.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged the speed at which laboratories can discover the viral composition and study health outcomes. The small ∼30-kb ssRNA genome of coronaviruses makes them adept at cross-species spread while enabling a robust understanding of all of the proteins the viral genome encodes. We have employed protein modeling, molecular dynamics simulations, evolutionary mapping, and 3D printing to gain a full proteome- and dynamicome-level understanding of SARS-CoV-2. We established the Viral Integrated Structural Evolution Dynamic Database (VIStEDD at RRID:SCR_018793) to facilitate future discoveries and educational use. Here, we highlight the use of VIStEDD for nsp6, nucleocapsid (N), and spike (S) surface glycoprotein. For both nsp6 and N, we found highly conserved surface amino acids that likely drive protein-protein interactions. In characterizing viral S protein, we developed a quantitative dynamics cross-correlation matrix to gain insights into its interactions with the angiotensin I-converting enzyme 2 (ACE2)-solute carrier family 6 member 19 (SLC6A19) dimer. Using this quantitative matrix, we elucidated 47 potential functional missense variants from genomic databases within ACE2/SLC6A19/transmembrane serine protease 2 (TMPRSS2), warranting genomic enrichment analyses in SARS-CoV-2 patients. These variants had ultralow frequency but existed in males hemizygous for ACE2. Two ACE2 noncoding variants (rs4646118 and rs143185769) present in ∼9% of individuals of African descent may regulate ACE2 expression and may be associated with increased susceptibility of African Americans to SARS-CoV-2. We propose that this SARS-CoV-2 database may aid research into the ongoing pandemic.

Balancing precision versus cohort transcriptomic analysis of acute and recovery phase of viral bronchiolitis.

Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor antiviral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved health care delivery. A cohort of PAXgene RNA sequencing of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics. Patients with severe bronchiolitis had signatures connected to the immune system, interferon signaling, and cytokine signaling, with marked sex differences in XIST, RPS4Y1, KDM5D, and LINC00278 for severity. Several patients had unique secondary infections, cytokine activation, immune responses, biological pathways, and immune cell activation, highlighting the need for defining patient-level transcriptomic signatures. Balancing relative contributions of cohort-based biomarker discoveries with patient's biological responses is needed to understand the totality of mechanisms of adverse outcomes in viral bronchiolitis.

Comprehensive Review of Topical Analgesics for Chronic Pain.

PURPOSE OF REVIEW: Topical analgesics are a non-opioid option for the treatment of chronic pain conditions including neuropathic pain, musculoskeletal pain, and osteoarthritis. There are many topical medications available; however their efficacy is variable. This article reviews the various topical analgesics, their mechanisms of action, and their efficacy. RECENT FINDINGS: Studies have found topical NSAIDs are useful in treating acute musculoskeletal pain syndromes (strains and sprains) and show some efficacy in treating hand and knee osteoarthritis (Derry et al. Cochrane Database Syst Rev 5:CD008609, 2017). Topical capsaicin 8% has been shown to be efficacious in the treatment of postherpetic neuralgia, painful diabetic peripheral neuropathy, and HIV-neuropathy (Derry et al. Cochrane Database Syst Rev 1:CD007393, 2017). Topical lidocaine has been widely studied and found to reduce pain in patients with postherpetic neuralgia (Knezevic et al. Pain Manag 7:537-58, 2017). Although many other topical analgesics are available, there is limited data to support the efficacy of other agents. Topical analgesics are a relatively benign treatment for chronic pain conditions including neuropathic pain, musculoskeletal, and myofascial pain. There is evidence to support the use of topical NSAIDs, high concentration topical capsaicin, and topical lidocaine for various painful conditions.

Interventional Modalities to Treat Complex Regional Pain Syndrome.

PURPOSE OF REVIEW: Complex regional pain syndrome (CRPS) is a debilitating pain condition that often requires a multidisciplinary approach including medication, physical therapy, occupational therapy, psychological therapy, and interventional procedures to restore the patient's quality of life. This article reviews the interventional treatments for pain resulting from CRPS. RECENT FINDINGS: Sympathetic nerve blocks (stellate ganglion and lumbar sympathetic) are the first-line interventional treatment options for patients with CRPS of the upper and lower extremities, respectively. Fluoroscopic techniques for lumbar sympathetic blocks have not significantly changed throughout the years. However, both novel fluoroscopic and ultrasound approaches to stellate ganglion blockade have arisen. In addition, novel neuromodulation therapies to treat CRPS have been developed to include new waveforms with dorsal column stimulation and entirely new nerve targets such as dorsal root ganglion stimulation. This paper will review the latest interventional treatment options available for the treatment of CRPS.

SARS-CoV-2-Encoded Proteome and Human Genetics: From Interaction-Based to Ribosomal Biology Impact on Disease and Risk Processes.

SARS-CoV-2 (COVID-19) has infected millions of people worldwide, with lethality in hundreds of thousands. The rapid publication of information, both regarding the clinical course and the viral biology, has yielded incredible knowledge of the virus. In this review, we address the insights gained for the SARS-CoV-2 proteome, which we have integrated into the Viral Integrated Structural Evolution Dynamic Database, a publicly available resource. Integrating evolutionary, structural, and interaction data with human proteins, we present how the SARS-CoV-2 proteome interacts with human disorders and risk factors ranging from cytokine storm, hyperferritinemic septic, coagulopathic, cardiac, immune, and rare disease-based genetics. The most noteworthy human genetic potential of SARS-CoV-2 is that of the nucleocapsid protein, where it is known to contribute to the inhibition of the biological process known as nonsense-mediated decay. This inhibition has the potential to not only regulate about 10% of all biological transcripts through altered ribosomal biology but also associate with viral-induced genetics, where suppressed human variants are activated to drive dominant, negative outcomes within cells. As we understand more of the dynamic and complex biological pathways that the proteome of SARS-CoV-2 utilizes for entry into cells, for replication, and for release from human cells, we can understand more risk factors for severe/lethal outcomes in patients and novel pharmaceutical interventions that may mitigate future pandemics.

Virus-induced genetics revealed by multidimensional precision medicine transcriptional workflow applicable to COVID-19.

Precision medicine requires the translation of basic biological understanding to medical insights, mainly applied to characterization of each unique patient. In many clinical settings, this requires tools that can be broadly used to identify pathology and risks. Patients often present to the intensive care unit with broad phenotypes, including multiple organ dysfunction syndrome (MODS) resulting from infection, trauma, or other disease processes. Etiology and outcomes are unique to individuals, making it difficult to cohort patients with MODS, but presenting a prime target for testing/developing tools for precision medicine. Using multitime point whole blood (cellular/acellular) total transcriptomics in 27 patients, we highlight the promise of simultaneously mapping viral/bacterial load, cell composition, tissue damage biomarkers, balance between syndromic biology versus environmental response, and unique biological insights in each patient using a single platform measurement. Integration of a transcriptome workflow yielded unexpected insights into the complex interplay between host genetics and viral/bacterial specific mechanisms, highlighted by a unique case of virally induced genetics (VIG) within one of these 27 patients. The power of RNA-Seq to study unique patient biology while investigating environmental contributions can be a critical tool moving forward for translational sciences applied to precision medicine.

A randomized-controlled trial of sugammadex versus neostigmine: impact on early postoperative strength.

BACKGROUND: Residual neuromuscular blockade after surgery is associated with airway obstruction, hypoxia, and respiratory complications. Compared with neostigmine, sugammadex reverses neuromuscular blockade to a train-of-four ratio > 0.9 more rapidly. It is unknown, however, whether the superior reversal profile of sugammadex improves clinically relevant measures of strength in the early postoperative period. METHODS: Patients undergoing general, gynecological, or urologic surgery were randomized to receive either neostigmine (70 µg·kg-1, maximum 5 mg) or sugammadex (2 or 4 mg·kg-1) to reverse neuromuscular blockade. The primary outcome was the ability to breathe deeply measured by incentive spirometry at 30, 60, and 120 min after reversal. RESULTS: We randomized 62 patients to either a neostigmine (n = 31) or sugammadex (n = 31) group. The incentive spirometry volume recovery trajectory was not different between the two groups (P = 0.35). Median spirometry volumes at baseline, 30, 60, and 120 min postoperatively were 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, and 1800 vs 1950 mL for the sugammadex and neostigmine groups, respectively. Postoperative incentive spirometry decrease from baseline was not different between the two groups. Hand grip strength, the ability to sit unaided, train-of-four ratio on postanesthesia care unit (PACU) admission, time to extubation, time to PACU discharge readiness, and Quality of Recovery-15 scores were also not different between the groups. CONCLUSIONS: Measures of postoperative strength, such as incentive spirometry, hand group strength, and the ability to sit up in the early postoperative period were not different in patients who received neostigmine or sugammadex for the reversal of neuromuscular blockade. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02909439); registered: 21 September, 2016.

RéSUMé: CONTEXTE: Les blocs neuromusculaires résiduels après une chirurgie sont associés à l'obstruction des voies aériennes, à l'hypoxie et à des complications respiratoires. Par rapport à la néostigmine, le sugammadex neutralise le bloc neuromusculaire à un ratio de train-de-quatre (TOF) > 0,9 plus rapidement. Nous ne savons toutefois pas si le profil de neutralisation supérieur du sugammadex améliore les mesures pertinentes d'un point de vue clinique de la force en période postopératoire initiale. MéTHODE: Nous avons randomisé des patients subissant une chirurgie générale, gynécologique ou urologique à recevoir de la néostigmine (70 µg·kg-1, maximum 5 mg) ou du sugammadex (2 ou 4 mg·kg-1) pour neutraliser le bloc neuromusculaire. Le critère d'évaluation principal était la capacité des patients à respirer profondément telle que mesurée par spirométrie incitative à 30, 60 et 120 min après la neutralisation. RéSULTATS: Au total, 62 patients ont été randomisés dans les groupes néostigmine (n = 31) ou sugammadex (n = 31). Aucune différence dans la trajectoire de récupération de volume de spirométrie incitative n'a été observée entre les deux groupes (P = 0,35). Les volumes médians de spirométrie préopératoire et à 30, 60 et 120 min postopératoires étaient de 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, et 1800 vs 1950 mL pour les groupes sugammadex et néostigmine, respectivement. La diminution postopératoire de la spirométrie incitative par rapport aux valeurs de base était similaire dans les deux groupes. La force de préhension, la capacité à s'asseoir sans assistance, le ratio de train-de-quatre à l'admission à la salle de réveil, le délai jusqu'à l'extubation, le délai jusqu'à l'obtention des critères de congé de la salle de réveil et les scores de QoR-15 (mesurant la qualité de récupération) ne différaient pas non plus entre les groupes. CONCLUSION: Les mesures de la force postopératoire, telles que la spirométrie incitative, la force de préhension et la capacité de s'asseoir en période postopératoire initiale, ne différaient pas entre les patients ayant reçu de la néostigmine ou du sugammadex pour neutraliser le bloc neuromusculaire. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT02909439); enregistrée le 21 septembre 2016.

Perioperative Quality Initiative consensus statement on postoperative blood pressure, risk and outcomes for elective surgery.

BACKGROUND: Postoperative hypotension and hypertension are frequent events associated with increased risk of adverse outcomes. However, proper assessment and management is often poorly understood. As a part of the PeriOperative Quality Improvement (POQI) 3 workgroup meeting, we developed a consensus document addressing this topic. The target population includes adult, non-cardiac surgical patients in the postoperative phase outside of the ICU. METHODS: A modified Delphi technique was used, evaluating papers published in MEDLINE examining postoperative blood pressure monitoring, management, and outcomes. Practice recommendations were developed in line with National Institute for Health and Care Excellence guidelines. RESULTS: Consensus recommendations were that (i) there is evidence of harm associated with postoperative systolic arterial pressure <90 mm Hg; (ii) for patients with preoperative hypertension, the threshold at which harm occurs may be higher than a systolic arterial pressure of 90 mm Hg; (iii) there is insufficient evidence to precisely define the level of postoperative hypertension above which harm will occur; (iv) a greater frequency of postoperative blood pressure measurement is likely to identify risk of harm and clinical deterioration earlier; and (v) there is evidence of harm from withholding beta-blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors in the postoperative period. CONCLUSIONS: Despite evidence of associations with postoperative hypotension or hypertension with worse postoperative outcome, further research is needed to define the optimal levels at which intervention is beneficial, to identify the best methods and timing of postoperative blood pressure measurement, and to refine the management of long-term antihypertensive treatment in the postoperative phase.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Perioperative Opioid Minimization in Opioid-Naïve Patients.

Surgical care episodes place opioid-naïve patients at risk for transitioning to new persistent postoperative opioid use. With one of the central principles being the application of multimodal pain interventions to reduce the reliance on opioid-based medications, enhanced recovery pathways provide a framework that decreases perioperative opioid use. The fourth Perioperative Quality Initiative brought together a group of international experts representing anesthesiology, surgery, and nursing with the objective of providing consensus recommendations on this important topic. Fourth Perioperative Quality Initiative was a consensus-building conference designed around a modified Delphi process in which the group alternately convened for plenary discussion sessions in between small group discussions. The process included several iterative steps including a literature review of the topics, building consensus around the important questions related to the topic, and sequential steps of content building and refinement until agreement was achieved and a consensus document was produced. During the fourth Perioperative Quality Initiative conference and thereafter as a writing group, reference applicability to the topic was discussed in any area where there was disagreement. For this manuscript, the questions answered included (1) What are the potential strategies for preventing persistent postoperative opioid use? (2) Is opioid-free anesthesia and analgesia feasible and appropriate for routine operations? and (3) Is opioid-free (intraoperative) anesthesia associated with equivalent or superior outcomes compared to an opioid minimization in the perioperative period? We will discuss the relevant literature for each questions, emphasize what we do not know, and prioritize the areas for future research.

Chronic Headache: a Review of Interventional Treatment Strategies in Headache Management.

PURPOSE OF THE REVIEW: To provide an overview of current interventional pain management techniques for primary headaches with a focus on peripheral nerve stimulation and nerve blocks. RECENT FINDINGS: Despite a plethora of treatment modalities, some forms of headaches remain intractable to conservative therapies. Interventional pain modalities have found a niche in treating headaches. Individuals resistant to common regimens, intolerant to pharmaceutical agents, or those with co-morbid factors that cause interactions with their therapies are some instances where interventions could be considered in the therapeutic algorithm. In this review, we will discuss these techniques including peripheral nerve stimulation, third occipital nerve block (TON), lesser occipital nerve block (LON), greater occipital nerve block (GON), sphenopalatine block (SPG), radiofrequency ablation (RFA), and cervical epidural steroid injections (CESI). Physicians have used several interventional techniques to treat primary headaches. While many can be treated pharmacologically, those who continue to suffer from refractory or severe headaches may see tremendous benefit from a range of more invasive treatments which focus on directly inhibiting the painful nerves. While there is a plethora of evidence suggesting these methods are effective and possibly durable interventions, there is still a need for large, prospective, randomized trials to clearly demonstrate their efficacy.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway.

Perioperative malnutrition has proven to be challenging to define, diagnose, and treat. Despite these challenges, it is well known that suboptimal nutritional status is a strong independent predictor of poor postoperative outcomes. Although perioperative caregivers consistently express recognition of the importance of nutrition screening and optimization in the perioperative period, implementation of evidence-based perioperative nutrition guidelines and pathways in the United States has been quite limited and needs to be addressed in surgery-focused recommendations. The second Perioperative Quality Initiative brought together a group of international experts with the objective of providing consensus recommendations on this important topic with the goal of (1) developing guidelines for screening of nutritional status to identify patients at risk for adverse outcomes due to malnutrition; (2) address optimal methods of providing nutritional support and optimizing nutrition status preoperatively; and (3) identifying when and how to optimize nutrition delivery in the postoperative period. Discussion led to strong recommendations for implementation of routine preoperative nutrition screening to identify patients in need of preoperative nutrition optimization. Postoperatively, nutrition delivery should be restarted immediately after surgery. The key role of oral nutrition supplements, enteral nutrition, and parenteral nutrition (implemented in that order) in most perioperative patients was advocated for with protein delivery being more important than total calorie delivery. Finally, the role of often-inadequate nutrition intake in the posthospital setting was discussed, and the role of postdischarge oral nutrition supplements was emphasized.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Patient-Reported Outcomes in an Enhanced Recovery Pathway.

Patient-reported outcomes (PROs) are measures of health status that come directly from the patient. PROs are an underutilized tool in the perioperative setting. Enhanced recovery pathways (ERPs) have primarily focused on traditional measures of health care quality such as complications and hospital length of stay. These measures do not capture postdischarge outcomes that are meaningful to patients such as function or freedom from disability. PROs can be used to facilitate shared decisions between patients and providers before surgery and establish benchmark recovery goals after surgery. PROs can also be utilized in quality improvement initiatives and clinical research studies. An expert panel, the Perioperative Quality Initiative (POQI) workgroup, conducted an extensive literature review to determine best practices for the incorporation of PROs in an ERP. This international group of experienced clinicians from North America and Europe met at Stony Brook, NY, on December 2-3, 2016, to review the evidence supporting the use of PROs in the context of surgical recovery. A modified Delphi method was used to capture the collective expertise of a diverse group to answer clinical questions. During 3 plenary sessions, the POQI PRO subgroup presented clinical questions based on a literature review, presented evidenced-based answers to those questions, and developed recommendations which represented a consensus opinion regarding the use of PROs in the context of an ERP. The POQI workgroup identified key criteria to evaluate patient-reported outcome measures (PROMs) for their incorporation in an ERP. The POQI workgroup agreed on the following recommendations: (1) PROMs in the perioperative setting should be collected in the framework of physical, mental, and social domains. (2) These data should be collected preoperatively at baseline, during the immediate postoperative time period, and after hospital discharge. (3) In the immediate postoperative setting, we recommend using the Quality of Recovery-15 score. After discharge at 30 and 90 days, we recommend the use of the World Health Organization Disability Assessment Scale 2.0, or a tailored use of the Patient-Reported Outcomes Measurement Information System. (4) Future study that consistently applies PROMs in an ERP will define the role these measures will have evaluating quality and guiding clinical care. Consensus guidelines regarding the incorporation of PRO measures in an ERP were created by the POQI workgroup. The inclusion of PROMs with traditional measures of health care quality after surgery provides an opportunity to improve clinical care.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Gastrointestinal Dysfunction Within an Enhanced Recovery Pathway for Elective Colorectal Surgery.

The primary driver of length of stay after bowel surgery, particularly colorectal surgery, is the time to return of gastrointestinal (GI) function. Traditionally, delayed GI recovery was thought to be a routine and unavoidable consequence of surgery, but this has been shown to be false in the modern era owing to the proliferation of enhanced recovery protocols. However, impaired GI function is still common after colorectal surgery, and the current literature is ambiguous with regard to the definition of postoperative GI dysfunction (POGD), or what is typically referred to as ileus. This persistent ambiguity has impeded the ability to ascertain the true incidence of the condition and study it properly within a research setting. Furthermore, a rational and standardized approach to prevention and treatment of POGD is needed. The second Perioperative Quality Initiative brought together a group of international experts to review the published literature and provide consensus recommendations on this important topic with the goal to (1) develop a rational definition for POGD that can serve as a framework for clinical and research efforts; (2) critically review the evidence behind current prevention strategies and provide consensus recommendations; and (3) develop rational treatment strategies that take into account the wide spectrum of impaired GI function in the postoperative period.

Functional Duration of Closure Systems Used in Partial Nephrectomy.

PURPOSE: We determined the functional life of various configurations of partial nephrectomy closure systems. MATERIALS AND METHODS: Sutures were prepared using standard techniques for sutured renorrhaphy during partial nephrectomy. Tested systems included knot/Hem-o-Lok®, Lapra-Ty®/Hem-o-Lok and Hem-o-Lok/Hem-o-Lok combinations. The saline filled tank was maintained at 37C. Vicryl®, Stratafix™ polyglycolic acid-polycaprolactone or V-Loc™ 180 sutures were suspended at 4 or 2 N. Suture material breakage or slippage was considered failure. RESULTS: At 4 N 20% of sutures terminated with knot/Hem-o-Lok failed by 3 weeks compared to 56% and 100% terminated with Lapra-Ty/Hem-o-Lok and Hem-o-Lok/Hem-o-Lok, respectively (p <0.0001). The 55% and 100% of failures with Lapra-Ty/Hem-o-Lok and Hem-o-Lok/Hem-o-Lok, respectively, were generally due to slippage vs 11% with knot/Hem-o-Lok (p <0.0001). Overall failure rates with Lapra-Ty/Hem-o-Lok for zero to 4-zero sutures were 41% with Vicryl, 82% with polyglycolic acid-polycaprolactone and 24% with V-Loc 180 (p <0.0001). The only sutures without failure at 4 N with Lapra-Ty/Hem-o-Lok and knot/Hem-o-Lok closure systems were Vicryl zero, and V-Loc 2-zero and 3-zero. At 2 N Lapra-Ty/Hem-o-Lok failure (17.5% vs 0%, p = 0.039) and Hem-o-Lok/Hem-o-Lok failure (39% vs 16%, p = 0.074) were more common with polyglycolic acid-polycaprolactone than with V-Loc sutures. CONCLUSION: Hem-o-Lok/Hem-o-Lok and Lapra-Ty/Hem-o-Lok combinations resulted in more frequent failures at 3 weeks or greater than knot/Hem-o-Lok. For all sutures tested knots were superior to Lapra-Tys to backstop Hem-o-Loks at 4 N. Preferably, Vicryl zero or V-Loc 2-zero/3-zero sutures should be used in combination with knots or Lapra-Tys at 4 N. Under these experimental conditions the Lapra-Ty/Hem-o-Lok combination did not reliably suspend the other sutures tested for 3 weeks. If Lapra-Ty/Hem-o-Lok or Hem-o-Lok/Hem-o-Lok combinations are used, we recommend closure at lesser tension and/or the use of appropriate sutures.

Retrograde Epidural Catheter Relieves Intractable Sacral Pain.

Pain caused by tumor infiltration of the sacral area remains a major clinical challenge. Patients with poor pain control despite comprehensive medical management may be treated with neuraxial techniques such as continuous epidural or spinal anesthetic. We report a case in which a patient with metastatic breast cancer experienced inadequate pain relief after multiple intravenous pain management regimens as well as intrathecal (IT) drug delivery. The concentration of local anesthetics delivered via the IT catheter was limited due to the patient's baseline motor weakness which would be exacerbated with higher concentrations of local anesthetics. Thus, a decision was made to insert an epidural catheter via a retrograde technique to provide the patient with a "band of anesthesia" which would provide profound sensory blockade without concomitant motor weakness. Pain refractory to other modalities of pain control was successfully treated with the epidural technique.

Two-Dimensional Fluctuation Correlation Spectroscopy (2D-FlucCS): A Method to Determine the Origin of Relaxation Rate Dispersion.

Relaxation rate dispersion, i.e., nonexponential or multicomponent kinetics, is observed in complex systems when measuring relaxation kinetics. Often, the origin of rate dispersion is associated with the heterogeneity in the system. However, both homogeneous (where all molecules experience the same rate but inherently nonexponential) and heterogeneous (where all molecules experience different rates) systems can exhibit rate dispersion. A multidimensional correlation analysis method has been demonstrated to detect and quantify rate dispersion observed in molecular rotation, diffusion, solvation, and reaction kinetics. One-dimensional (1D) autocorrelation function detects rate dispersion and measures its extent. Two-dimensional (2D) autocorrelation function measures the origin of rate dispersion and distinguishes homogeneous from heterogeneous. In a heterogeneous system, implicitly there exist subensembles of molecules experiencing different rates. A three-dimensional (3D) autocorrelation function measures subensemble exchange if present and reveals if the system possesses static or dynamic heterogeneity. This perspective discusses the principles, applications, and potential and also presents a future outlook of two-dimensional fluctuation correlation spectroscopy (2D-FlucCS). The method is applicable to any experiment or simulation where a time series of fluctuation in an observable (emission, scattering, current, etc.) around a mean value can be obtained in steady state (equilibrium or nonequilibrium), provided the system is ergodic.

Outpatient Ketamine Infusions for the Treatment of Fibromyalgia and Chronic Pain Syndrome: A Case Report.

Intravenous (IV) ketamine has demonstrable efficacy for chronic pain management. Its use in an outpatient setting has provided relief from myriad pain syndromes and additionally may reduce dependence on opioids. Nevertheless, its long-term ability to provide these benefits is understudied. Here, we present the case of a 68-year-old female who presented to our clinic with persistent fibromyalgia, accompanied by other pain symptoms that had been recalcitrant to traditional pain management therapy including nerve blocks, ablations, spinal cord stimulation, and morphine medication. We administered seven increasing IV ketamine doses over two weeks. The patient reported significant, widespread pain relief. The patient continued to receive IV ketamine twice weekly for over a year and remains on this schedule. Pain relief has persisted under this regimen, along with a demonstrable improvement in quality of life, a reduced use of morphine, and the cessation of anti-depressant medication. This case indicates that long-term ketamine infusions show promise for chronic pain management and that more longitudinal studies on this treatment are warranted.

Maintenance IV Ketamine Therapy in the Fibromyalgia Patient: A Case Report.

Introduction: Fibromyalgia is a complex disorder characterized by distributed and persistent pain often associated with fatigue and depression. The underlying causal agents of this dysfunction are not clear. Ketamine has been used to treat chronic pain in a variety of pain syndromes, including fibromyalgia, but the dosing protocols used are neither standardized nor consistent across cases. The current case presents an opportunity to contribute to a progression towards a consensus on ketamine dosing for fibromyalgia. Case Presentation: A 60-year-old female presented with indications of fibromyalgia and was administered a 9-session IV ketamine treatment for pain. The initial dosing was 50 mg, with a concentration of 1.0 mg/ml at an infusion rate of 0.8 mg/kg/hr. This was increased to 200 mg and eventually to 240 mg, maintaining a ketamine concentration 4.0-4.8 mg/ml at an infusion rate of 1.5 mg/kg/hr. Management and Outcomes: Following the first 9-session therapy, the patient reported >50% pain relief from pre-infusion levels and was placed on a maintenance regimen in perpetuity. This regimen involves two monthly IV ketamine infusions, one day apart for two hours at a maintenance rate of 4.8 mg/kg/hr. Conclusion: Ketamine by IV is an effective option for pain management in patients with fibromyalgia. Compared to previous case studies, it is recommended that increased total dose, frequent administration, and longer duration of infusions all may be necessary for ketamine to maximize its beneficial effects.

Spontaneous Regression and Separation of Idiopathic Epiretinal Membranes.

Epiretinal membranes (ERMs) typically remain stable or progressively worsen. Here, we report two rare cases of spontaneous ERM regression and one case of ERM separation. This is a case series of three patients. The patients' clinical data were collected and ERMs were evaluated with serial optical coherence tomographies (OCTs). Cases one and two were female patients presenting with floaters. Mild-to-moderate idiopathic ERM was diagnosed which spontaneously regressed over the following years without intervention and evidence of separation. Patients' vision was slightly decreased or remained stable, respectively. Case three was a female patient presenting with blurry vision. A mild ERM was diagnosed with vitreomacular traction (VMT) and a tiny macular hole. Over the following three months, ERM separation along with VMT release was evidenced on OCT. The macular hole healed simultaneously. Her vision improved from 20/70 to 20/30. The possibility of spontaneous regression of idiopathic ERMs should be a factor to consider in management. Further research must be done to determine the mechanism of this phenomenon.