bluuebunny/crossref_metadata_2025 huggingface dataset:
Dexmedetomidine 2 ppm Is Appropriate for the Enhancement Effect of Local Anesthetic Action of Lidocaine in Inferior Alveolar Nerve Block
Authors: Ouchi Kentaro
Published: May 2020

Objective:

Local anesthesia is essential for pain management in dentistry. The duration of anesthetic action of the addition of 5.0 and 7.5 ppm of dexmedetomidine (DEX) was significantly longer than the addition of adrenaline, and the mean duration of anesthetic action of the addition of 2.5 ppm DEX was also longer than the addition of adrenaline. We hypothesized that it is possible to safely achieve an equal local anesthesia effect as with 1:80,000 adrenaline, without using adrenaline or felypressin, by the addition of <2.5 ppm DEX to the local anesthetic solution.

Materials and Methods:

Nineteen healthy volunteers were randomly assigned by a computer to receive 1.8 mL of 1 of 3 drug combinations (1.8% lidocaine with 1.0 ppm [1.8 μg] DEX, lidocaine with 2.0 ppm [3.6 μg] DEX or lidocaine with 1:80,000 [22.5 μg] adrenaline), to produce inferior alveolar nerve block. Pulp latency and lower lip numbness (for assessing onset and duration of anesthesia) were tested, and sedation level, blood pressure, and heart rate were recorded every 2 minutes for 10 minutes, every 5 minutes from 10 to 20 minutes, and every 10 minutes from 20 to 60 minutes.

Results:

Pulp latency increased compared with the baseline, from 4 minutes until 60 minutes; there were no significant intergroup differences at any timepoint. Anesthesia onset did not differ between groups. Anesthesia duration did not differ between groups. Blood pressure and heart rate did not change in any group. Sedation score did not indicate deep sedation in any of the groups.

Discussion:

DEX at a concentration of 1.0 to 2.0 ppm enhances the local anesthetic action of lidocaine. DEX at 2.0 ppm produces similar enhancement of local anesthesia effect as the addition of 1:80,000 adrenaline.
The Evolution of an Interdisciplinary Developmental Round in a Surgical Neonatal Intensive Care Unit
Authors: Griffiths Nadine , James-Nunez Kristen , Spence Kaye , Crowle Cathryn , Pettigrew Jane , Loughran-Fowlds Alison
Published: May 2020

Background:

Developmentally supportive environments are known to improve medical outcomes for hospitalized neonates and are considered the overarching philosophy for practice in the neonatal setting. Developmental rounds are a strategy incorporated by multidisciplinary teams to support development within and beyond the neonatal unit. Typically, they consist of bedside consultations and individualized developmentally supportive recommendations for families and clinicians. Globally, the use of developmental rounds has been described since the early 1990s. They are viewed as a measure to counter some of the barriers to developmental care implementation while buffering against the effect of an intensive care admission. To date, their use in the surgical neonatal intensive care unit (sNICU) has been minimally reported in literature.

Purpose:

This article describes the focus and work of a developmental round team and strategy in the sNICU.

Method:

A retrospective audit of developmental round key performance criteria undertaken over a 4-year period (2015-2018).

Findings/Results:

More than 300 developmental consults and 2000 individualized developmental recommendations occurred annually. Parental presence during the developmental round increased by 10%, from 48% to 58%, during the audit period.

Implications for Practice/Implications for Research:

Literature has supported the use of developmental round interventions; however, minimal data have been reported to date. This article provides retrospective audit data of a developmental round intervention in the sNICU with a focus on data over 4 years to highlight key areas, including the structure and process, recommended educational standards for team members, and parental engagement, as key markers for developmental round efficacy. Future research should focus on the link between the developmental round intervention and long-term neonatal outcomes.
Cannabinoids for Pain Control During Medical Abortion
Authors: Colwill Alyssa Covelli , Alton Katie , Bednarek Paula H. , Bayer Lisa L. , Jensen Jeffrey T. , Garg Bharti , Beardsworth Kathleen , Edelman Alison
Published: May 2020

OBJECTIVE:

To evaluate whether prophylactic dronabinol, a synthetic tetrahydrocannabinol, reduces pain during medical abortion.

METHODS:

We conducted a randomized, double-blind, placebo-controlled trial of women undergoing medical abortion with mifepristone and misoprostol up through 70 days of gestation. All participants received 800 mg of ibuprofen and were randomized to either 5 mg of oral dronabinol or a placebo 30 minutes before misoprostol administration. Participants used a text messaging service to report pain on a numeric rating scale from 0 to 10 (0=no pain, 10=worst pain). The primary outcome was maximum pain experienced during the 24 hours after misoprostol administration. Secondary outcomes were pain scores at 0, 6, and 24 hours after misoprostol administration; maximum anxiety and nausea scores; use of additional pain medication; reported side effects; and satisfaction (yes or no). We needed 68 participants (34 per group) to have 80% power to detect a 2-point difference in maximum pain on a numeric rating scale.

RESULTS:

From November 2018 to May 2019, we randomized 70 women (dronabinol=35, placebo=35). Participants in the study arms had comparable baseline characteristics. We found no difference between groups in the median maximum pain score reported (dronabinol 7 [interquartile range 6–8], placebo 7 [interquartile range 5–8], P=.82) or median pain scores at any timepoint. Groups were also no different in mean maximum anxiety (dronabinol 3.33 [SD 3.06], placebo 3.23 [SD 2.53], P=.88) or nausea scores (dronabinol 2.21 [SD 2.32], placebo 2.72 [SD 2.64], P=.41). Most women were satisfied with their pain management (76% dronabinol, 82% placebo, P=.51).

CONCLUSION:

Dronabinol does not reduce the maximum level of pain experienced by women undergoing medical abortion.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03604341.
Ovarian Cancer After Prophylactic Salpingectomy in a Patient With Germline BRCA1 Mutation
Authors: Lugo Santiago Nicole , Smith Evan , Cox Mary , Wan Carrie S. , Tchabo Nana E. , Awowole Ibraheem , Broach Vance , Chi Dennis S.
Published: May 2020

BACKGROUND:

Women with germline BRCA1 or BRCA2 mutations have a lifetime risk of ovarian cancer of up to 46%. Opportunistic salpingectomy has been advocated as a risk-reducing strategy owing to increasing recognition of tubal origin, yet evidence of efficacy in this high-risk population is limited.

CASE:

This is the case of a woman with a BRCA1 mutation who underwent prophylactic mastectomy and bilateral salpingectomy with ovarian retention before the age of 40 years. She did not undergo oophorectomy and subsequently developed stage IV high-grade serous ovarian cancer 4 years after her initial surgery.

CONCLUSION:

More research is needed to determine the role of prophylactic salpingectomy with delayed oophorectomy, optimal timing of completion oophorectomy, and the risks and benefits compared with up-front risk-reducing salpingo-oophorectomy.
Association of Prior Cesarean Delivery With Early Term Delivery and Neonatal Morbidity
Authors: Forde Braxton , DeFranco Emily A.
Published: May 2020

OBJECTIVE:

To assess whether a history of prior cesarean delivery is associated with an increased risk of earlier delivery timing and resultant neonatal morbidity.

METHODS:

We performed a population-based retrospective cohort study using U.S. birth certificate data, 2012–2016. The study population included women with one or more prior cesarean deliveries compared with a referent group of parous women without prior cesarean delivery. To enrich for a population with minimized risk factors for early delivery, we excluded women with history of preterm birth, pregnancies complicated by multifetal gestation, pregnancy-induced hypertension, anomaly, small for gestational age, or malpresentation. Analyses were limited to births from 35 to 42 weeks of gestation. Women with a vaginal birth after cesarean delivery were excluded. The primary outcome was the risk of birth at each week of gestational age. Secondary outcomes included adverse neonatal and maternal outcomes.

RESULTS:

Patients were stratified by number of prior cesarean deliveries (one, two, three, or four or more) compared with parous patients without prior cesarean delivery. The adjusted relative risk (aRR) of delivery at 35 weeks of gestation was highest in women with four or more prior cesarean deliveries (aRR 2.79, 95% CI 2.74–2.82). Prior cesarean delivery also had a significant influence on neonatal morbidity. As the number of prior cesarean deliveries increased, the risk of composite neonatal morbidity increased, from 8.0% (aRR 1.5, 95% CI 1.48–1.51) with one prior cesarean delivery up to 21.0% (aRR 4.9, 95% CI 4.76–5.04) with four or more prior cesarean deliveries compared with a baseline risk of 5.5% in parous women without prior cesarean delivery.

CONCLUSION:

Prior cesarean delivery is correlated with earlier delivery and increased neonatal morbidity. Advocating trial of labor after cesarean delivery may provide maternal and neonatal benefit.
Influence of Contraception Class on Incidence and Severity of Acne Vulgaris
Authors: Barbieri John S. , Mitra Nandita , Margolis David J. , Harper Cynthia C. , Mostaghimi Arash , Abuabara Katrina
Published: May 2020

OBJECTIVE:

To evaluate the association of different contraceptive methods on the incidence and severity of acne.

METHODS:

Using a de-identified commercial claims database, we performed a retrospective cohort study evaluating the incidence of clinical encounters for acne in the first year after initiation of contraception among female patients aged 12–40 years who were new contraceptive users. To evaluate the association of contraception class with acne severity, a subgroup analysis was performed among a cohort of patients with a history of acne examining the incidence of treatment escalation from topical acne medications to an oral tetracycline-class antibiotic in the year after initiation of contraception.

RESULTS:

Among new contraceptive users with no history of acne (N=336,738), compared with combined oral contraceptives (OCs), the copper intrauterine device (IUD) (hazard ratio [HR] 1.14; 95% CI 1.01–1.29) and levonorgestrel IUDs (HR 1.09; 95% CI 1.03–1.16) were associated with increased risk of clinical encounters with acne. Among those with a history of acne (n=21,178), compared with combined OCs, the copper IUD (HR 1.44; 95% CI 1.00–2.06) and levonorgestrel IUDs (HR 1.34; 95% CI 1.10–1.64) were associated with increased risk of treatment escalation from topical acne medications to an oral tetracycline class antibiotic.

CONCLUSION:

Combined OCs appear to be associated with a modest (or small) protective effect with respect to incident acne and treatment escalation compared with other contraceptive methods. However, absolute differences between contraceptive methods were small.
Intraoperative Identification of Clavicle Fracture Patterns: Do Clavicles Fail in a Predictable Pattern?
Authors: Drayer Nicholas J. , Dukes Chase A. , Dudevoir Michelle L. , Greenhouse Alyssa R. , Rao Meghana V. , Arrington Edward D. , Friedman Richard J. , Grassbaugh Jason A. , Eichinger Josef K.
Published: May 2020

Objectives:

To characterize the fracture pattern and pattern of fragmentation for displaced, midshaft clavicle fractures undergoing operative management.

Design:

Prospective observational study.

Setting:

Two institutions. Level 1 and Level 2 Trauma Centers.

Patients/Participants:

Fifty-three patients who underwent operative repair of midshaft clavicle fracture.

Intervention:

All clavicles were treated by operative open reduction internal fixation.

Main Outcome Measurements:

All clavicles were categorized by the Robinson classification based on injury plain film bilateral upright clavicle radiographs. In addition, intraoperative fracture characteristics of fragment length and location were measured and recorded to evaluate the fracture pattern. All fractures were analyzed to determine the frequency of segmental comminution versus length-stable patterns, analyze characteristics of butterfly fragment size, number and location as well as the location of the cortical read for those length-stable fractures.

Results:

Analysis revealed 55% were Robinson 2B2 based on preoperative radiographs. Length-stable, anatomic reduction was achievable in 83%. For those in which an anatomic cortical read was achievable, 97.7% had a read present in the posterior-superior aspect of the clavicle.

Conclusions:

Midshaft clavicle fractures that meet conventional criteria for operative repair occur in a predictable manner with butterfly fragments generated from anterior-inferior compression and simple fracture line generated from tension along the posterior-superior aspect of the clavicle. Understanding this pattern can assist in the in surgical planning.
Electric Scooter Orthopaedic Injury Demographics at an Urban Level I Trauma Center
Authors: Siow Matthew Y. , Lavoie-Gagne Ophelie , Politzer Cary S. , Mitchell Brendon C. , Harkin William E. , Flores Alec R. , Schwartz Alexandra K. , Girard Paul J. , Kent William T.
Published: May 2020

Objectives:

This study highlights demographics and orthopaedic injuries of electric scooter–related trauma that presented to our institution over a 27-month period.

Design:

Retrospective review.

Setting:

Urban Level 1 trauma center.

Patients:

Patients presenting to the emergency department, trauma bay, or outpatient clinic after electric scooter injury were identified from November 2017 through January 2020 using ICD-10 diagnosis codes.

Main Outcomes:

Patient charts were reviewed for demographics, injury characteristics, imaging, treatment, perioperative data, and Injury Severity Scores.

Results:

Four hundred eighty-five patients presented during the study period. Of these, 44% had orthopaedic injuries, including 30% with pelvis or extremity fractures. There were 21 (10%) polytraumatized patients in the orthopaedic cohort. The age ranged from 16 to 79 years (average 36 years), with 58% men, and 18% were visitors from out of town. Of 49 patients requiring orthopaedic surgery, 8 underwent surgery on an urgent basis. The average Injury Severity Score for orthopaedic patients was 8.4 with a median of 5.0 for nonoperative injuries versus a significantly higher median of 16.0 for operative injuries. Twenty-nine percent of patients were intoxicated and only 2% wore a helmet.

Conclusions:

Electric scooter injuries are increasing, and many patients sustain high-energy injuries. As electric scooter use continues to increase, the prevalence of orthopaedic injuries is also likely to rise. Further studies are needed to fully understand the impact scooter-related injuries have on individual patients and the health care system.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
The Lateral Stress Radiograph Identifies Occult Instability of Lateral Compression Pelvic Ring Injuries Without Sedation
Authors: Parry Joshua A. , Salameh Motasem , Maher Michael H. , Stacey Stephen C. , Mauffrey Cyril
Published: May 2020

Objectives:

To determine if pelvic ring displacement on the lateral stress radiograph (LSR) correlated with displacement on examination under anesthesia (EUA).

Design:

Retrospective cohort study.

Setting:

Urban Level I trauma center.

Patients/Participants:

Twenty consecutive patients with unilateral minimally displaced LC1 injuries with complete sacral fractures.

Intervention:

An anteroposterior pelvis radiograph taken in the lateral decubitus position (LSR) was performed on awake patients before EUA in the operating room.

Main Outcome Measurements:

Correlation between ≥1 cm of pelvic ring displacement on the LSR and EUA.

Results:

The LSR demonstrated ≥1 cm of displacement in 11 of the 20 patients (55%). All of these patients had ≥1 cm of displacement on EUA and underwent surgical fixation. The remaining 9 patients with <1 cm of displacement on the LSR also had <1 cm of displacement on EUA and were managed nonoperatively.

Conclusions:

The LSR reliably identified occult instability in LC1 pelvic ring injuries and demonstrated 100% correlation with EUA. In contrast to EUA, the LSR does not require sedation and normalizes the amount of force applied to determine instability.

Level of Evidence:

Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Association Between IV Thiamine and Mortality in Patients With Septic Shock: A Nationwide Observational Study
Authors: Miyamoto Yoshihisa , Aso Shotaro , Iwagami Masao , Yasunaga Hideo , Matsui Hiroki , Fushimi Kiyohide , Hamasaki Yoshifumi , Nangaku Masaomi , Doi Kent
Published: May 2020

Objectives:

To examine the effect of thiamine administration on mortality in patients with septic shock requiring norepinephrine.

Design:

Retrospective observational cohort study from July 2010 to March 2017.

Setting:

More than 1,000 acute care hospitals covering approximately 90% of all tertiary care emergency hospitals in Japan.

Patients:

Patients with septic shock requiring norepinephrine within 2 days of admission were retrospectively reviewed.

Interventions:

Patients who received greater than or equal to 100 mg of thiamine within 2 days of admission were included in the thiamine group and those who did not were included in the control group.

Measurements and Main Results:

We identified a total of 68,571 eligible patients, including 18,780 and 49,791 patients in the thiamine and control groups, respectively. In the thiamine group, 100 and 200 mg of thiamine per day were administered to 10,143 (54.0%) and 7,679 (40.9%) patients, respectively. The 28-day mortality were 19.2% (3,609/18,780) and 17.8% (8,845/49,791) in the thiamine and control groups, respectively. After adjusting for confounders by inverse probability of treatment weighting, no significant differences were observed between the two groups (risk difference, 0.2%; 95% CI, –0.5% to 0.9%). There were also no significant differences between the 100-mg thiamine group and the control group (risk difference, 0.6%; 95% CI, –0.3% to 1.4%) or between the 200-mg thiamine group and the control group (risk difference, –0.3%; 95% CI, –1.3% to 0.8%).

Conclusions:

The findings of this nationwide database-based observational study did not support an association between thiamine administration early after admission and the 28-day mortality in patients with septic shock.
Staging 18F-FDG PET/CT influences the treatment plan in melanoma patients with satellite or in-transit metastases
Authors: Holtkamp Lodewijka H.J. , Chakera Annette H. , Fung Sebastian , Stretch Jonathan R. , Saw Robyn P.M. , Lee Kenneth , Ch’ng Sydney , Gonzalez Maria , Thompson John F. , Emmett Louise , Nieweg Omgo E.
Published: May 2020

Whole-body positron emission tomography/computed tomography (PET/CT) and brain magnetic resonance imaging (MRI) are commonly used to stage patients with palpable lymph node metastases from melanoma, but their role in patients with satellite and/or in-transit metastasis (S&ITM) is unclear. The aim of this study was to establish the diagnostic value of PET/CT and brain MRI in these patients, and to assess their influence on subsequent management decisions. In this prospective study, 25 melanoma patients with a first presentation of S&ITM who had no clinical evidence of palpable nodal or distant metastasis underwent whole-body 18F-FDG PET/CT and brain MRI after a tentative pre-scan treatment plan had been made. Sensitivity and specificity of imaging were determined by pathological confirmation, clinical outcome and repeat PET/CT and MRI at 6 months. PET/CT led to a modification of the initial treatment plan in four patients (16%). All four were upstaged (AJCC stage eighth edition). PET/CT was false-positive in one patient, who had a Schwannoma in his trapezius muscle. A thyroid carcinoma was an incidental finding in another patient. The sensitivity of PET/CT was 58% and specificity 83%. In 6 months following the baseline PET/CT, further sites of in-transit or systemic disease were identified in 10 patients (40%). Brain MRI did not alter the treatment plan or change the disease stage in any patient. Whole-body PET/CT improved staging in melanoma patients with S&ITM and changed the originally-contemplated treatment plan in 16%. MRI of the brain appeared not to be useful.
MC1R variants and cutaneous melanoma risk according to histological type, body site, and Breslow thickness: a pooled analysis from the M-SKIP project
Authors: Caini Saverio , Gandini Sara , Botta Francesca , Tagliabue Elena , Raimondi Sara , Nagore Eduardo , Zanna Ines , Maisonneuve Patrick , Newton-Bishop Julia , Polsky David , Lazovich DeAnn , Kumar Rajiv , Kanetsky Peter A. , Hoiom Veronica , Ghiorzo Paola , Landi Maria Teresa , Ribas Gloria , Menin Chiara , Stratigos Alexander J. , Palmieri Giuseppe , Guida Gabriella , García-Borrón Jose Carlos , Nan Hongmei , Little Julian , Sera Francesco , Puig Susana , Fargnoli Maria Concetta
Published: May 2020

Little is known on whether melanocortin 1 receptor (MC1R) associated cutaneous melanoma (CM) risk varies depending on histological subtype and body site, and whether tumour thickness at diagnosis (the most important prognostic factor for CM patients) differs betweenMC1Rvariant carriers and wild-type individuals. We studied the association betweenMC1Rvariants and CM risk by histological subtype, body site, and Breslow thickness, using the database of the M-SKIP project. We pooled individual data from 15 case-control studies conducted during 2005–2015 in Europe and the USA. Study-specific, multi-adjusted odds ratios were pooled into summary odds ratios (SOR) and 95% confidence intervals (CI) using random-effects models. Six thousand eight hundred ninety-one CM cases and 5555 controls were included. CM risk was increased amongMC1Rvariant carriers vs. wild-type individuals. The increase in risk was comparable across histological subtypes (SOR for any variant vs. wild-type ranged between 1.57 and 1.70, always statistical significant) except acral lentiginous melanoma (ALM), for which no association emerged; and slightly greater on chronically (1.74, 95% CI 1.47–2.07) than intermittently (1.55, 95% CI 1.34–1.78) sun-exposed skin. CM risk was greater for those carrying ‘R’ vs. ‘r’ variants; correlated with the number of variants; and was more evident among individuals not showing the red hair colour phenotype. Breslow thickness was not associated withMC1Rstatus.MC1Rvariants were associated with an increased risk of CM of any histological subtype (except ALM) and occurring on both chronically and intermittently sun-exposed skin.
Pedunculated Perianal Mass in a Neonate: A Rare Case Report
Authors: Aihole Jayalaxmi Shripati
Published: May 2020

Congenital perianal pedunculated masses are a rare occurrence in neonates. They are benign in nature and can be excised completely for definitive diagnosis. Here is a report of a rare case of pedunculated perianal mass occurring in a neonate managed successfully.
Fertility and Endocrine Preservation in the Management of Colorectal Cancer in Women
Authors: Chae-Kim Jennifer , Hayslip Clifford C.
Published: May 2020

Case Summary:

A 28-year-old nulliparous woman presented with rectal bleeding. Colonoscopy revealed a 4-cm malignant-appearing mass in the proximal rectum, and biopsies confirmed invasive adenocarcinoma of the rectum. Computed tomography scan showed no evidence of metastatic disease. Staging MRI found transmural extension with minimal stranding in the adjacent fat, as well as no evidence of pathological pelvic adenopathy, consistent with a T3N0 lesion. The proposed treatment plan involved neoadjuvant chemotherapy and radiation therapy before primary surgical resection. The patient desired fertility preservation and was referred immediately to Reproductive Endocrinology and Infertility. She underwent assisted reproduction with oocyte and blastocyst cryopreservation followed by laparoscopic ovarian transposition. Nine months after surgical low anterior resection of the tumor and completion of her cancer treatment, her ovaries were repositioned to their normal pelvic position during an ileostomy takedown procedure. She underwent a frozen embryo transfer but did not conceive. She resumed menses and later conceived spontaneously. Her pregnancy was complicated by cervical incompetence, requiring cervical cerclage. She delivered a live male infant via cesarean delivery at 32 weeks gestation, approximately 2 years after completion of cancer therapy. Four years after diagnosis, the patient remains in remission with undetectable CEA levels.
A multicenter, randomized study to select the minimum effective dose of estetrol (E4) in postmenopausal women (E4Relief): part 1. Vasomotor symptoms and overall safety
Authors: Gaspard Ulysse , Taziaux Mélanie , Mawet Marie , Jost Maud , Gordenne Valérie , Coelingh Bennink Herjan J.T. , Lobo Rogerio A. , Utian Wulf H. , Foidart Jean-Michel
Published: May 2020

Objective:

The aim of this study was to select the minimum effective dose of estetrol (E4) for the treatment of vasomotor symptoms in postmenopausal women.

Methods:

This was a multicenter, randomized, double-blind, placebo-controlled study. Postmenopausal women (n = 257, of whom 32 were hysterectomized) aged 40 to 65 years, with ≥7 moderate to severe hot flushes (HFs) per day, or 50 or more moderate to severe HFs weekly, received 2.5, 5, 10, or 15 mg E4, or placebo once-daily for a period of 12 weeks. Efficacy was assessed by recording the frequency and severity of HFs. Overall safety was assessed by recording adverse events, measuring endometrial thickness, and monitoring bleeding patterns. Treatment groups were compared using analysis of covariance.

Results:

The frequency of moderate to severe HFs decreased with all E4 doses. The difference in the percentage change of weekly HF frequency was significant for 15 mg E4 versus placebo at both W4 (−66% vs −49%, P = 0.032) and W12 (−82% vs −65%, P = 0.022). The decrease in severity of HFs was significantly more pronounced for 15 mg E4 than for placebo at both W4 (−0.59 vs −0.33, P = 0.049) and W12 (−1.04 vs −0.66, P = 0.049); the other doses failed to achieve statistical significance. In nonhysterectomized women, endometrial thickness increased during treatment and normalized following progestin treatment at study completion. No endometrial hyperplasia was observed.

Conclusions:

Estetrol 15 mg is considered to be the minimum effective daily oral dose for treatment of vasomotor symptoms. Its current seemingly favorable safety profile is further to be confirmed in phase 3 clinical development.

Video Summary:

http://links.lww.com/MENO/A591.
Diagnosis and Treatment of Polycystic Ovary Syndrome in Adolescent Females
Authors: EBERSOLE ASHLEY M. , BONNY ANDREA E.
Published: May 2020

The diagnosis of polycystic ovary syndrome (PCOS) in adolescents is complicated by the overlap of normal puberty with features of PCOS. To address this difficulty, recent diagnostic guidelines have worked to modify adult diagnostic criteria for use in adolescents. These guidelines stress that a definitive diagnosis of PCOS is not needed to initiate treatment. Deferring diagnosis, while providing symptom treatment and regular follow-up, is one recommended option. Treatment options for PCOS should be individualized to the presentation, needs, and preferences of each patient. The goals of treatment are to improve the quality of life and long-term health outcomes.
Combined treatment with epoxyeicosatrienoic acid analog and 20-hydroxyeicosatetraenoic acid antagonist provides substantial hypotensive effect in spontaneously hypertensive rats
Authors: Gawrys Olga , Husková Zuzana , Baranowska Iwona , Walkowska Agnieszka , Sadowski Janusz , Kikerlová Soňa , Vaňourková Zdeňka , Honetschlägerová Zuzana , Škaroupková Petra , Červenka Luděk , Falck John R. , Imig John D. , Kompanowska-Jezierska Elzbieta
Published: May 2020

Objectives:

The global morbidity and mortality related to hypertension and associated disorders increases continuously and novel therapeutic strategies are still in high demand. Increasing evidence suggests the important role in blood pressure regulation of cytochrome P-450-dependent metabolites of arachidonic acid. Epoxyeicosatrienoic acids (EETs) induce vasodilation and natriuresis, and have renoprotective and anti-inflammatory properties. 20-HETE is an arachidonic acid metabolite with both prohypertensive and antihypertensive activities. To explore the pathophysiological role of arachidonic acid metabolites in more detail, we examined the antihypertensive efficiency of EET-A, a stable analog of 14,15-EET, and of AAA, a novel antagonist of the 20-HETE receptors.

Methods:

Male spontaneously hypertensive rats (SHR) were treated for 5 weeks with EET-A, AAA or the combination; age-matched untreated SHR and normotensive Wistar–Kyoto rats served as controls. EET-A and AAA were administered in drinking water at 10 mg/kg/day each. SBP was measured by telemetry and urine, blood, and tissue samples were collected for relevant analyses.

Results:

EET-A or AAA given alone had no significant effect on SHR blood pressure. In contrast, combined treatment with AAA and EET-A was significantly antihypertensive, causing a decrease in SBP from 180 ± 3 to 160 ± 5 mmHg (P < 0.05). Additionally, the combined treatment attenuated cardiac hypertrophy, decreased kidney ANG II level, increased natriuresis, and increased the excretion of nitric oxide metabolites.

Conclusion:

Considering the beneficial impact of the combined treatment with EET-A and AAA on SHR blood pressure and cardiovascular and renal function, we suggest that the treatment is a promising therapeutic strategy for human hypertension.
Association between secondhand smoke exposure and hypertension: nearly as large as smoking
Authors: Skipina Travis M. , Soliman Elsayed Z. , Upadhya Bharathi
Published: May 2020

Active smoking is a widely accepted risk factor for cardiovascular disease and is recognized as a major public health problem. Passive smoking, also known as secondhand smoke exposure (SHSE), is thought to have similar cardiovascular consequences and the risk has been postulated to be equivalent to that of active smoking. A major component of this risk involves the connection with chronic hypertension. There are several population-based observational studies investigating the relationship between SHSE and chronic hypertension, all of which demonstrate a positive association. Given that SHSE appears to be a risk factor for chronic hypertension, SHSE should also be a risk factor for hypertensive end-organ disease. Many studies have sought to investigate this relationship, but this has yet to be fully elucidated. In this review, we focus on the current evidence regarding the association between SHSE and hypertension as well as exploration of the links between SHSE and hypertensive end-organ damage.
Effects of Amifostine Pre-treatment on miRNA, lncRNA, and mRNA Profiles in the Hypothalamus of Mice Exposed to 60Co Gamma Radiation
Authors: Tian Baolei , Fu Hangjiang , Liu Bin , Zhu Jie , Zheng Xiaofei , Ge Changhui
Published: May 2020

There is increasing evidence that the expression of non-coding RNA and mRNA (messenger RNA) is significantly altered following high-dose ionizing radiation (IR), and their expression may play a critical role in cellular responses to IR. However, the role of non-coding RNA and mRNA in radiation protection, especially in the nervous system, remains unknown. In this study, microarray profiles were used to determine microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA expression in the hypothalamus of mice that were pretreated with amifostine and subsequently exposed to high-dose IR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. We found that fewer miRNAs, lncRNAs, and mRNAs were induced by amifostine pre-treatment in exposed mice, which exhibited antagonistic effects compared to IR, indicating that amifostine attenuated the IR-induced effects on RNA profiles. GO and KEGG pathway analyses showed changes in a variety of signaling pathways involved in inflammatory responses during radioprotection following amifostine pre-treatment in exposed mice. Taken together, our study revealed that amifostine treatment altered or attenuated miRNA, lncRNA, and mRNA expression in the hypothalamus of exposed mice. These data provide a resource to further elucidate the mechanisms underlying amifostine-mediated radioprotection in the hypothalamus.
Punching a Graft for Descemet Membrane Endothelial Keratoplasty Onto a Contact Lens Reduces Endothelial Cell Loss at the Graft's Margin
Authors: Achiron Asaf , Nahum Yoav , Adler Avital , Nisgav Yael , Bahar Irit , Livny Eitan
Published: May 2020

Purpose:

To evaluate whether punching Descemet membrane endothelial keratoplasty (DMEK) corneal grafts onto a contact lens scaffold reduces endothelial cell loss at the graft margin in comparison to punching the graft directly onto the donor stroma.

Methods:

DMEK grafts were prepared using 2 different methods after peeling the graft from the stroma: punching onto a contact lens and punching onto the donor stroma. The grafts were then evaluated for the width of Descemet membrane devoid of endothelial cells in the peripheral ring, measured at 4 points at the graft margin.

Results:

Our study included 6 grafts, harvested from 3 donors aged 66.3 ± 5.1 years. Grafts prepared on a contact lens scaffolding had more of their Descemet membrane margin populated by endothelial cells than did grafts that were punched directly onto the donor stroma (total denuded area: 0.06 ± 0.08 mm2 vs. 1.17 ± 0.02 mm2, P = 0.018; maximal width of denuded area: 59.6 ± 28.4 μm vs. 100.2 ± 59.7 μm, P = 0.07). Donor grafts on contact lens had approximately 2.5% more endothelial cells available for transplantation (2425 cells/mm2 vs. 2367 cells/mm2). Graft preparation time did not significantly differ between the methods (6.4 ± 0.49 vs. 9.8 ± 3.7 minutes, P = 0.46).

Conclusions:

Punching DMEK grafts onto a contact lens reduces endothelial loss at the grafts’ margins and may prolong their survival.
Spitz melanoma secondary to xeroderma pigmentosa in a child: a case report
Authors: Gao Zhengjun , Chang Shilin
Published: May 2020

A 6-year-old boy presented with a 5-year history of pigmentation on the face, neck, and hands. On examination, the patient had extreme photophobia. There was multiple freckles-like pigmentations on the face, neck, and back of both hands. Extremities were densely distributed. Multiple facial lesions, 1–2 cm2 in size, were also seen; most of them were ulcerated and had crusty patches. There was mild double eversion of the lower eyelids, with pigmentation and conjunctival redness in both eyes. Facial histopathologic findings: Spitz nevus-like malignant melanoma, Clark grade IV. A final diagnosis of melanoma secondary to xeroderma pigmentosa was made. According to the previous literature, the minimum age of patients with xeroderma pigmentosum combined with malignant melanoma is 8 years old, but the age, in this case, is 6 years old. In addition, extensive local excision of suspicious lesions early is of great significance for the prognosis of patients.
“Pseudophakic Reverse Pupillary Block” Following Yamane Technique Scleral-fixated Intraocular Lens
Authors: Bharathi Mahesh , Balakrishnan Divya , Senthil Sirisha
Published: May 2020

Purpose:

The authors report a rare complication of “pseudophakic reverse pupillary block” after a secondary, scleral-fixated intraocular lens implantation using the Yamane technique.

Methods/Results:

A 52-year-old male patient was referred for uncontrolled intraocular pressure (IOP) despite 3 topical antiglaucoma medications in his right eye (RE). Elevated IOP occurred after the RE cataract surgery performed elsewhere 1 year ago. On examination, the RE visual acuity was 20/60, IOP was 28 mm Hg, the iris showed mid-peripheral transillumination defects with iris chaffing, posterior bowing of the iris with a deep anterior chamber, pigment dispersion, and scleral-fixated intraocular lens (SFIOL). Ultrasound biomicroscopy showed a deep anterior chamber with posterior bowing of iris with concave iris configuration with iridolenticular contact with the SFIOL, suggestive of reverse pupillary block. After laser peripheral iridotomy, the iris moved forward into planar position, iridolenticular contact was relieved with a resolution of the pupillary block, and the IOP reduced to 14 mm Hg.

Conclusions:

The present case describes a rare complication of “pseudophakic reverse pupillary block” after a glued SFIOL implantation. The probable mechanism for the pupillary block is the reduced gap between the posterior surface of iris and optic of the IOL. This is likely caused by the loss of 5-degree posterior angulation of the 3-piece IOL because of stretching of the haptics leading to an increase in the iridolenticular contact and reverse pupillary block and elevated IOP. The persistent anterior chamber inflammation as a result of iris chaffing and pigment dispersion could also contribute to compromised trabecular outflow and further IOP elevation.

Reverse pupillary block can occur after a glued SFIOL implantation that can be relieved by a laser peripheral iridotomy. The authors recommend either preoperative laser peripheral iridotomy or surgical iridectomy intraoperatively in eyes with a glued intraocular lens to prevent this rare complication.
COVID-19 in Neonates and Infants: Progression and Recovery
Authors: Ng Khuen Foong , Bandi Srini , Bird Paul William , Wei-Tze Tang Julian
Published: May 2020

Between March 10, 2020 and April 17, 2020, of 8/70 (11.4%) SARS-CoV-2 positive infants that presented, 5/8 (63%) developed fever, 4/8 (50%) had lower respiratory tract involvement, 2/8 (25%) had neutropenia and thrombocytosis, and 4/8 infants (50%) were treated for suspected sepsis with broad-spectrum antibiotics. Only 1/8 (13%) required pediatric intensive care. All patients were eventually discharged home well.
Children Hospitalized With Severe COVID-19 in Wuhan
Authors: Wang Yanli , Zhu Feng , Wang Cheng , Wu Jing , Liu Jie , Chen Xue , Xiao Han , Liu Zhisheng , Wu Zubo , Lu Xiaoxia , Ma Jiehui , Zeng Ye , Peng Hua , Sun Dan
Published: May 2020

Background:

Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children.

Methods:

A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children’s Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed.

Results:

Eight of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis.

Conclusions:

More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.
Palpebral Pleomorphic Adenomas of the Lacrimal Gland
Authors: Vahdani Kaveh , Rose Geoffrey E.
Published: May 2020

Aims:

To report the characteristics and management for patients with palpebral pleomorphic adenoma of the lacrimal gland.

Methods:

The records for patients with palpebral pleomorphic adenoma seen at Moorfields Eye Hospital between 1978 and 2019 were reviewed for demographics, presentation, imaging, histopathology, management, and outcome.

Results:

Forty-three patients (25 male; 58%) with palpebral pleomorphic adenoma were identified, presenting at a mean age of 46 years (median 46.4 years; range 24–81 years) with symptoms for an average of 31 months (median 18.0 months; range 1 month to 17 years). The commonest symptom was a painless upper lid lump (37 patients; 86%), although 4 patients (9%) had a localized ache, and 1 (2%) had episodic epiphora. A moderately-mobile, firm round mass (like a “chick-pea”) was readily palpable in 39/43 (91%) patients, and significant ptosis and upper lid swelling was noted in 6 cases (14%). Imaging was reviewed in 35 patients, 28 (80%) having a well-defined homogeneous mass in front of the orbital rim, on the anterior pole of the lacrimal gland. With the exception of 8 tumors removed from the actual palpebral lobe using a conjunctival incision, all others were excised intact through an upper eyelid skin-crease incision. Histopathology confirmed an intact pseudocapsule in 39/43 (91%) and 10 (23%) had a mild chronic lymphocytic inflammation within the tumor and/or neighboring lacrimal gland. There were no tumor recurrences at an average follow-up of 40 months (median 9.1; range 2 weeks to 230 years).

Conclusion:

Most palpebral pleomorphic adenomas are discovered as an upper lid lump and a few first become manifest as upper lid swelling with ptosis. To avoid inadvertent incisional biopsy, they should be recognized preoperatively—especially as most are readily palpable as a hard lump superotemporally, often freely mobile in the suborbicularis plane (anterior to the tarsus and main lacrimal gland). Excision, generally easiest through a transcutaneous route, was judged intact in all cases and confirmed in 91% of histological reports, with no recurrent tumors.
Corneal lenticule extraction assisted by a low-energy femtosecond laser
Authors: Izquierdo Luis , Sossa Daniel , Ben-Shaul Or , Henriquez Maria A.
Published: May 2020

A lenticule of intrastromal corneal tissue was cut together with 2 small incisions of 3.0 mm using a low-energy femtosecond laser system, FEMTO LDV Z8; 1 incision led to the posterior plane and 1 to the anterior, allowing dissection of the lenticule. When needed, recentering of the treatment area was possible without repeating the docking stage. Five eyes were operated, and a complete dissection and removal of the lenticule was achieved in all cases without any intraoperative complications. In addition, at postoperative day 1, all patients had a clear cornea. In conclusion, guided lenticule extraction using a low-energy femtosecond laser was a promising and easy procedure.
Differential expression of cerebrospinal fluid neuroinflammatory mediators depending on osteoarthritis pain phenotype
Authors: Flores Bjurström Martin , Bodelsson Mikael , Montgomery Agneta , Harsten Andreas , Waldén Markus , Janelidze Shorena , Hall Sara , Hansson Oskar , Irwin Michael R. , Mattsson-Carlgren Niklas
Published: May 2020

Neuroinflammation is implicated in the development and maintenance of persistent pain states, but there are limited data linking cerebrospinal fluid (CSF) inflammatory mediators with neurophysiological pain processes in humans. In a prospective observational study, CSF inflammatory mediators were compared between patients with osteoarthritis (OA) who were undergoing total hip arthroplasty due to disabling pain symptoms (n = 52) and pain-free comparison controls (n = 30). In OA patients only, detailed clinical examination and quantitative sensory testing were completed. Cerebrospinal fluid samples were analyzed for 10 proinflammatory mediators using Meso Scale Discovery platform. Compared to controls, OA patients had higher CSF levels of interleukin 8 (IL-8) (P = 0.002), intercellular adhesion molecule 1 (P = 0.007), and vascular cell adhesion molecule 1 (P = 0.006). Osteoarthritis patients with central sensitization possibly indicated by arm pressure pain detection threshold <250 kPa showed significantly higher CSF levels of Fms-related tyrosine kinase 1 (Flt-1) (P = 0.044) and interferon gamma-induced protein 10 (IP-10) (P = 0.024), as compared to subjects with PPDT above that threshold. In patients reporting pain numerical rating scale score ≥3/10 during peripheral venous cannulation, Flt-1 was elevated (P = 0.025), and in patients with punctate stimulus wind-up ratio ≥2, CSF monocyte chemoattractant protein 1 was higher (P = 0.011). Multiple logistic regression models showed that increased Flt-1 was associated with central sensitization, assessed by remote-site PPDT and peripheral venous cannulation pain, and monocyte chemoattractant protein-1 with temporal summation in the area of maximum pain. Multiple proinflammatory mediators measured in CSF are associated with persistent hip OA-related pain. Pain phenotype may be influenced by specific CSF neuroinflammatory profiles.
Impaired alcohol-induced dopamine release in the nucleus accumbens in an inflammatory pain model: behavioral implications in male rats
Authors: Campos-Jurado Yolanda , Lorente Jesús David , González-Romero José Luis , Granero Luis , Polache Ana , Hipólito Lucía
Published: May 2020

Recent studies have drawn the attention to the link between alcohol use disorder and the presence of pain. Indeed, the correct management of pain in patients with a previous history of alcohol use disorder has been reported to decrease the risk of relapse in alcohol drinking, suggesting that in this prone population, pain may increase the vulnerability to relapse. Previous data in male rats revealed that inflammatory pain desensitizes mu-opioid receptors in the ventral tegmental area and increases intake of high doses of heroin. Owing to the relevant role of mu-opioid receptors in alcohol effects, we hypothesize that pain may also alter alcohol reinforcing properties and therefore affect alcohol relapse in male rats. Our microdialysis studies show that the presence of inflammatory pain blunted the increase of extracellular dopamine levels in the nucleus accumbens induced by 1.5 g/kg of ethanol (s.c.). Moreover, we also revealed that the administration of 52 nmol of ethanol into the ventral tegmental area failed to induce place preference only in inflammatory pain-suffering animals, and a higher dose (70 nmol) was necessary to reverse this effect. Finally, we evaluated the effect of inflammatory pain on the alcohol deprivation effect in long-term ethanol-experienced male rats. After 4 cycles of free ethanol intake and abstinence periods, inflammatory pain induced alcohol deprivation effect without affecting its magnitude. These intriguing data reveal the impact of pain on neurochemical and behavioral effects after alcohol administration but also underscore the necessity of finding an appropriate paradigm to determine the long-term behavioral consequences.