The potential role of lactulose pharmacotherapy in the treatment and prevention of diabetes.

The non-absorbable disaccharide lactulose is mostly used in the treatment of various gastrointestinal disorders such as chronic constipation and hepatic encephalopathy. The mechanism of action of lactulose remains unclear, but it elicits more than osmotic laxative effects. As a prebiotic, lactulose may act as a bifidogenic factor with positive effects in preventing and controlling diabetes. In this review, we summarized the current evidence for the effect of lactulose on gut metabolism and type 2 diabetes (T2D) prevention. Similar to acarbose, lactulose can also increase the abundance of the short-chain fatty acid (SCFA)-producing bacteria Lactobacillus and Bifidobacterium as well as suppress the potentially pathogenic bacteria Escherichia coli. These bacterial activities have anti-inflammatory effects, nourishing the gut epithelial cells and providing a protective barrier from microorganism infection. Activation of peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP1) can influence secondary bile acids and reduce lipopolysaccharide (LPS) endotoxins. A low dose of lactulose with food delayed gastric emptying and increased the whole gut transit times, attenuating the hyperglycemic response without adverse gastrointestinal events. These findings suggest that lactulose may have a role as a pharmacotherapeutic agent in the management and prevention of type 2 diabetes via actions on the gut microbiota.

Effect of Stress Ball Use or Hand-holding on Anxiety During Skin Cancer Excision: A Randomized Clinical Trial.

Importance: Patients undergoing skin surgery under local anesthesia can experience anxiety. Adjuvant intraoperative anxiety reduction methods may help. Objectives: To assess whether hand-holding or holding a stress ball reduces patient anxiety during excisional surgery of head or neck skin cancer with the patient under local anesthesia and to measure pain and patient satisfaction. Design, Setting, and Participants: In this nonblinded, single-center randomized clinical trial, performed from January 24 through April 26, 2017, at a dermatology outpatient service in an urban, academic medical center, a consecutive sample of 135 adults who required excisional removal of nonmelanoma skin cancer of the head or neck was randomized and studied. Interventions: Participants were randomized 1:1:1 to 3 groups: hand-holding, stress ball, or control (treatment as usual). Participants in the hand-holding group had a female researcher hold one of their hands during administration of anesthesia and extirpation, and those in the stress ball group held a round compressible ball and squeezed it as desired during the same period. Main Outcomes and Measures: The primary outcome was anxiety, measured by a visual analog scale (VAS), 6-item State Trait Anxiety Inventory (STAI), and physiologic measures (blood pressure and heart rate). Secondary outcomes were pain during the procedure and overall participant satisfaction. In addition, participants were asked how many hours they spent researching the procedure before surgery. Results: A total of 135 participants, 45 per study arm, were enrolled (mean [SD] age, 65.5 [13.9] years; 84 [62.2%] male; 134 [99.3%] white). There were no withdrawals or dropouts. Anxiety decreased over time in all groups, but no significant differences were found in the 3 anxiety measures across the 3 groups (VAS anxiety score before: control group, 3.11; hand-holding group, 3.04; stress ball group, 3.09 [P > .99]; VAS anxiety score during: control group, 1.89; hand-holding group, 2.31; stress ball group, 2.47 [P = .55]; STAI score: control group, 8.91; hand-holding group, 8.93; stress ball group, 8.76 [P = .96]). The 3 groups also did not significantly differ in postprocedure pain scores (control group, 0.78; hand-holding group, 0.64; stress ball group, 0.67; P = .85). Almost all participants (134 [99.2%]) were very satisfied. Participants who had done research had higher preoperative VAS anxiety scores (researched, 3.84; did not research, 2.62; P = .04). Conclusions and Relevance: Hand-holding and squeezing a stress ball do not appear to provide incremental anxiety reduction in patients during excisional skin cancer surgery. It is possible that some subgroups may respond better or that patients may respond better when able to select and tailor their preferred anxiety reduction method. Trial Registration: ClinicalTrials.gov identifier: NCT02816996.

Quantification of noninvasive fat reduction: A systematic review.

BACKGROUND AND OBJECTIVE: Noninvasive fat reduction appears effective, but there are various methods for quantifying changes. The objective of this review is to assess comparative utility measures of subcutaneous fat. STUDY DESIGN/MATERIALS AND METHODS: Articles describing noninvasive fat reduction were searched using MEDLINE, EMBASE, CINAHL and Scopus electronic databases on two dates (January 28, 2014 and February 16, 2016). Titles of studies and abstracts were screened for eligibility. Manual review was performed by two investigators to detect those that: (1) included original data; (2) were randomized controlled trials, or prospective or retrospective cohort studies; (3) quantified fat outcomes; and (4) enrolled at least 10 subjects. RESULTS: Of 1,057 retrieved articles, 36 met criteria. Most reported four or more measurement techniques. Circumference measurements were most commonly cited. Other objective techniques, like caliper thickness, ultrasound, magnetic resonance imaging (MRI), and three-dimensional (3D) photography, were also used. Common subjective methods were evaluation of standardized photographs by blinded raters and patient satisfaction surveys. CONCLUSIONS: For quantifying noninvasive fat reduction, all available methods had significant limitations: photographic comparisons were subjective; circumference or caliper measurements were confounded; ultrasound was operator dependent; MRI was expensive; computed models and simulations were in early development. As new technologies are developed, the need for reliable, accurate and practical measures of subcutaneous fat will increase. Lasers Surg. Med. 50:96-110, 2018. © 2017 Wiley Periodicals, Inc.

Laser Safety in Isotretinoin Use: A Survey of Expert Opinion and Practice.

BACKGROUND: Reports of poor wound healing in the setting of isotretinoin treatment have created a conservative standard of care in which laser and phototherapy treatment of patients receiving isotretinoin is relatively contraindicated. OBJECTIVE: A survey of 220 nationally recognized experts in cutaneous laser surgery was conducted to evaluate physician experience and opinion pertaining to laser and light procedures in patients treated with isotretinoin, including perceived risk and actual complications. RESULTS: There was a 42% response rate. Seventy-six percent of respondents have never seen in their own clinical practices any cases of complications arising in patients treated with laser while receiving isotretinoin or within 6 months of completing a course of therapy. Almost half of respondents have treated patients in this subpopulation with laser, although only a small minority have done so with ablative devices. Common concerns among respondents regarding isotretinoin patients are the risks of poor wound healing and scarring, but the most often reported concern is medicolegal risk (74%). CONCLUSION: It would seem that the risk of performing laser procedures on patients receiving isotretinoin or having recently completed a course, as estimated and observed by cutaneous laser experts, is lower than the currently perceived risk among the general medical community.

Safety of Local Intracutaneous Lidocaine Anesthesia Used by Dermatologic Surgeons for Skin Cancer Excision and Postcancer Reconstruction: Quantification of Standard Injection Volumes and Adverse Event Rates.

BACKGROUND: Intracutaneous lidocaine is used for anesthesia in dermatologic surgery for skin cancer excision and repair with exceedingly low incidence of reported adverse events. OBJECTIVE: To measure (1) the quantity of lidocaine typically used for facial skin cancer excision and reconstruction; and (2) the frequency and character of associated adverse events. METHODS: Survey study of dermatologic surgeons with longitudinal reporting. Reported practice during 10 business days: (1) mean volume of 1% lidocaine per skin cancer excision; (2) maximum per excision; (3) mean per reconstruction; and (4) maximum per reconstruction. RESULTS: A total of 437 of 1,175 subjects contacted (37.2%) responded. Mean per excision was 3.44 mL (SD: 2.97), and reconstruction 11.70 mL (10.14). Maximum per excision was 6.54 mL (4.23), and reconstruction was 15.85 mL (10.39). No cases of lidocaine toxicity were reported, diagnosed, or treated. Incidence of adverse events possibly anesthesia related was >0.15%, with most (0.13%) being mild cases of dizziness, drowsiness, or lightheadedness from epinephrine tachycardia. CONCLUSION: Toxicity associated with local anesthesia other than lidocaine was not studied. Volumes of lidocaine in skin cancer excision and repair are modest and within safe limits. Lidocaine toxicity is exceedingly rare to entirely absent. For comparable indications, lidocaine is safer than conscious sedation or general anesthesia.

Developmental PCB exposure increases susceptibility to audiogenic seizures in adulthood.

Developmental exposure to polychlorinated biphenyls (PCBs) causes auditory deficits. Thus, we recently conducted a study to investigate if developmental PCB exposure would exacerbate noise-induced hearing loss in adulthood. Unexpectedly, some PCB-exposed rats exhibited seizure-like behaviors when exposed to loud noise. Therefore, we conducted the current experiment to determine if adult rats perinatally exposed to PCBs are more susceptible to audiogenic seizures when tested in a standard audiogenic seizure paradigm. Adult male and female rats exposed to PCBs during gestation and lactation (0, 1, 3 or 6 mg/kg/day) and previously tested in the noise-induced hearing loss study were presented with a 100 dB noise stimulus. If they did not exhibit clonus in response to the 100 dB noise, they were exposed to a 105 dB stimulus 24-48 h later. This was followed by an 110 dB stimulus 24-48 h later if they did not exhibit clonus at 105 dB. Female and male rats exposed to either 3 or 6 mg/kg PCBs exhibited a significantly higher incidence of audiogenic seizures, shorter latency to onset of seizures, and greater severity of seizures compared to controls. Thyroxine measured in littermates at weaning was significantly lower in all PCB groups compared to controls, suggesting a potential mechanism for the increased incidence of audiogenic seizures. This is the first study to show that developmental PCB exposure increases the susceptibility to audiogenic seizures in adulthood.

Treatment of keratosis pilaris with 810-nm diode laser: a randomized clinical trial.

IMPORTANCE: Keratosis pilaris (KP) is a common skin disorder of follicular prominence and erythema that typically affects the proximal extremities, can be disfiguring, and is often resistant to treatment. Shorter-wavelength vascular lasers have been used to reduce the associated erythema but not the textural irregularity. OBJECTIVE: To determine whether the longer-wavelength 810-nm diode laser may be effective for treatment of KP, particularly the associated skin roughness/bumpiness and textural irregularity. DESIGN, SETTING, AND PARTICIPANTS: We performed a split-body, rater-blinded, parallel-group, balanced (1:1), placebo-controlled randomized clinical trial at a dermatology outpatient practice of an urban academic medical center from March 1 to October 1, 2011. We included all patients diagnosed as having KP on both arms and Fitzpatrick skin types I through III. Of the 26 patients who underwent screening, 23 met our enrollment criteria. Of these, 18 patients completed the study, 3 were lost to or unavailable for follow-up, and 2 withdrew owing to inflammatory hyperpigmentation after the laser treatment. INTERVENTIONS: Patients were randomized to receive laser treatment on the right or left arm. Each patient received treatment with the 810-nm pulsed diode laser to the arm randomized to be the treatment site. Treatments were repeated twice, for a total of 3 treatment visits spaced 4 to 5 weeks apart. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the difference in disease severity score, including redness and roughness/bumpiness, with each graded on a scale of 0 (least severe) to 3 (most severe), between the treated and control sites. Two blinded dermatologists rated the sites at 12 weeks after the initial visit. RESULTS: At follow-up, the median redness score reported by the 2 blinded raters for the treatment and control sides was 2.0 (interquartile range [IQR], 1-2; P = .11). The median roughness/bumpiness score was 1.0 (IQR, 1-2) for the treatment sides and 2.0 (IQR, 1-2) for the control sides, a difference of 1 (P = .004). The median overall score combining erythema and roughness/bumpiness was 3.0 (IQR, 2-4) for the treatment sides and 4.0 (IQR, 3-5) for the control sides, a difference of 1 (P = .005). CONCLUSIONS AND RELEVANCE: Three treatments with the 810-nm diode laser may induce significant improvements in skin texture and roughness/bumpiness in KP patients with Fitzpatrick skin types I through III, but baseline erythema is not improved. Complete treatment of erythema and texture in KP may require diode laser treatment combined with other laser or medical modalities that address redness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01281644.

Development of a scatter correction technique and its application to HDR 192Ir multicatheter breast brachytherapy.

This article introduces a scatter correction (SC) technique for high-dose-rate (HDR) 192Ir brachytherapy dose calculations in the absence of a full scatter environment near the skin. The technique uses dosimetry data derived by Monte Carlo (MC) simulations for the Nucletron microSelectron v2 HDR 192Ir source. The data include the primary and scatter components of the radial dose function and the anisotropy function in addition to a SC table. The dose to a point of interest for each dwell position is estimated by first calculating the primary and scatter doses in an infinite water phantom. The scatter dose is then scaled by a SC factor that depends on the distances between the point of interest, the dwell positions, and the body contour of the patient. SC calculations in water phantoms of three different shapes, as well as computed tomography-based geometries of 18 multicatheter breast patients, are compared with Task Group 43 (TG-43) and PTRAN_CT MC calculations. The SC calculations show improvement over TG-43 for all test cases while taking 50% longer to run. The target and skin doses for the breast patient plans are unaffected by tissue inhomogeneities, as indicated by an agreement better than 1% between the SC and MC results. On average, TG-43 overestimates the target coverage by 2% and the dose to the hottest 0.1 cm3 (D0.1 cc) of the skin by 5%. The low-density lung causes the lung and heart D0.1 cc to differ by up to 3% for the SC method and by 2%-5% for TG-43 compared with MC calculations. The SC technique is suitable for HDR 192Ir dose calculations near the skin provided that the dose is nearly unperturbed by internal inhomogeneities. It has been validated for multicatheter breast brachytherapy.

Patient-specific Monte Carlo dose calculations for high-dose-rate endorectal brachytherapy with shielded intracavitary applicator.

PURPOSE: An integrated software platform was developed to perform a patient-specific dosimetric study on high-dose-rate (192)Ir endorectal brachytherapy. Monte Carlo techniques were used to examine the perturbation effects of an eight-channel intracavitary applicator with shielding and a liquid-inflatable balloon. Such effects are ignored in conventional treatment planning systems that assume water-equivalent geometries. METHODS AND MATERIALS: A total of 40 Task Group 43-based rectal patient plans were calculated using the PTRAN_CT Monte Carlo photon transport code. The silicone applicator, tungsten or lead shielding, contrast solution-filled balloon, and patient anatomy were included in the simulations. The dose to water and dose to medium were scored separately. The effects of heterogeneities and uncertainties in source positioning were examined. A superposition calculation method using pregenerated Monte Carlo dose distributions about the shielded applicator in water was developed and validated for efficient treatment planning purposes. RESULTS: On average, metal shielding decreases the mean dose to the contralateral normal tissues by 24% and reduces the target volume covered by the prescribed dose from 97% to 94%. Tissue heterogeneities contribute to dose differences of <1% relative to the prescribed dose. The differences in the dose volume indices between dose to water and dose to medium-based calculations were <1% for soft tissues, <2% for bone marrow, and >20% for cortical bone. A longitudinal shift of +/-2.5 mm and a rotational shift of +/-15 degrees in applicator insertion reduced the target volume receiving the prescribed dose by

Dosimetric characterization of a novel intracavitary mold applicator for 192Ir high dose rate endorectal brachytherapy treatment.

The dosimetric properties of a novel intracavitary mold applicator for 192Ir high dose rate (HDR) endorectal cancer treatment have been investigated using Monte Carlo (MC) simulations and experimental methods. The 28 cm long applicator has a flexible structure made of silicone rubber for easy passage into cavities with deep-seated tumors. It consists of eight source catheters arranged around a central cavity for shielding insertion, and is compatible for use with an endocavitary balloon. A phase space model of the HDR source has been validated for dose calculations using the GEANT4 MC code. GAFCHROMIC EBT model film was used to measure dose distributions in water around shielded and unshielded applicators with two loading configurations, and to quantify the shielding effect of a balloon injected with an iodine solution (300 mg I/mL). The film calibration procedure was performed in water using an 192Ir HDR source. Ionization chamber measurements in a Lucite phantom show that placing a tungsten rod in the applicator attenuates the dose in the shielded region by up to 85%. Inserting the shielded applicator into a water-filled balloon pushes the neighboring tissues away from the radiation source, and the resulting geometric displacement reduces the dose by up to 53%; another 8% dose reduction can be achieved when the balloon is injected with an iodine solution. All experimental results agree with the GEANT4 calculations within measurement uncertainties.