Case Report: Optimum excision with split skin graft closure in the management of penile sebaceous carcinoma.

Sebaceous carcinoma (SC) is a rare malignant skin neoplasm derived from the meibomian gland of adnexal epithelium, which is frequently confused with basal cell carcinoma (BCC), exhibiting sebaceous differentiation and commonly found in the head and neck regions. We report a case of penile sebaceous carcinoma, an extremely rare anatomical site for SC. A 68-year-old man presented with a 4-month history of painless, non-healing ulcerated nodules over the left side of the penile shaft. Wedge biopsy showed adenocarcinoma with signet ring differentiation. We proceeded with wide local excision (WLE) of the lesion with the inclusion of the indurated skin and 5 mm of normal margin, followed by primary closure of the scrotal defect and split skin grafting of the penile shaft by using a thigh skin donor. The final histopathological examination revealed sebaceous carcinoma with pagetoid spread. The patient achieved recurrence-free survival without any form of adjuvant therapy after 4 years of follow-up.

The effects of hydrogen treatment in a cigarette smoke solution-induced chronic obstructive pulmonary disease-like changes in an animal model.

Background: Molecular hydrogen, with its antioxidant and anti-inflammatory properties, may be suitable for the prevention and treatment of chronic obstructive pulmonary disease (COPD). This study aims to investigate the therapeutic efficacy of hydrogen-oxygen (H2/O2) treatment in cigarette smoke solution (CSS)-induced COPD-like injury in a female BALB/c mouse model. Methods: Thirty mice were randomly assigned to three groups: Control (n=8), COPD (n=10), and COPD + H2/O2 (n=12). CSS was administered by intraperitoneal (IP) injection twice weekly for 6 weeks during the COPD induction phase. Simultaneously, the COPD + H2/O2 group started received 75 minutes of inhalation therapy (42% H2) delivered by the Oxy-Hydrogen Generator twice daily for 9 weeks. Mice body weights and survival were measured throughout the study period. Neutrophil elastase (NE) activity and lung histopathological changes were also evaluated. Results: The results showed a higher survival rate in the COPD + H2/O2 group compared to the COPD group (100% vs. 80%) during the induction phase. Slight decreases in body weight gains were observed in the COPD and COPD + H2/O2 groups during the first 15 days of the induction phase, but there was no significant difference in mean body weights among the three groups throughout the study period. NE activity was numerically lower in the COPD + H2/O2 group compared to the COPD group. The histopathological evaluation showed significant improvements in the H2/O2-treated mice with respect to mean linear intercept (MLI) and lesion (inflammation and emphysema) scores. Improvements in goblet cell hypertrophy and hyperplasia of airway epithelium were not significant. Conclusions: A 9-week H2/O2 inhalation therapy delivered by the Oxy-Hydrogen Generator to CSS-induced COPD-like injury in mice showed improvement in survival rate, alveolar structural changes, and histopathological lesion scores of the lung.

Prospective Evaluation of Pain and Anxiety Levels Between Wide-Awake Local Anesthesia No Tourniquet and General Anesthesia With Tourniquet in Excision of Wrist Ganglions.

Purpose: Excision of wrist ganglions is a common procedure in hand surgery. Our objective was to determine whether the type of anesthesia (general anesthesia [GA] vs wide-awake local anesthesia no tourniquet [WALANT] technique) would affect patient satisfaction regarding intraoperative pain control, postoperative pain management, and anxiety. Methods: This was a prospective study with patients divided into either the WALANT or GA cohort. The waiting time for surgery, Amsterdam Preoperative Anxiety and Information Scale, blood pressure, and heart rate were measured. Postsurgical questionnaires with the visual analog scale were completed. The surgeon's feedback on the ease of ganglion stalk visibility and usage of diathermy as a measure of a bloodless field was recorded. Patients reported the amount of analgesia consumed and overall satisfaction with the operation via the Surgical Satisfaction-8 questionnaire. Results: A total of 42 patients underwent wrist ganglion excision in 2 orthopedic centers over a period of 2 years, with 21 undergoing GA and 22 undergoing WALANT. The GA group was more anxious about anesthetic use with a higher demand for information about GA (P = .04). The duration of surgery was significantly shorter in the WALANT group and with a lower diathermy usage (P < .001). There was no difference in terms of surgical difficulty and stalk visualization. The visual analog scale pain score was significantly lower in the WALANT group than in the GA group immediately after surgery (P = .04) and on discharge (P = .004). While at home for 2 weeks, the WALANT group (mean = 2.91 tablets) consumed significantly fewer analgesic tablets than the GA group (mean = 6.25 tablets). However, both groups were satisfied with their experience. Conclusions: Wide-awake local anesthesia no tourniquet technique in the excision of ganglions provides another option of anesthesia with painless experiences, and no pain rebound after surgery. Patients were less anxious about WALANT than GA. Excision can be performed without diathermy usage with similar visualization of the stalk. Type of study/level of evidence: Therapeutic II.

Intravenous fentanyl vs. topical lignocaine for ProSeal™ laryngeal mask airway insertion with propofol induction.

Insertion of the laryngeal mask airway (LMA) without muscle relaxant requires adequate obtundation of airway reflexes, which may otherwise lead to incorrect or failed LMA placement. This study compared topical lignocaine spray vs. intravenous (IV) fentanyl, during propofol induction for insertion of the ProSeal™ LMA (PLMA). This was a prospective, randomized, double blind study, in ASA I or II patients, for elective or emergency surgery. Seventy patients (n = 70) who fulfilled the inclusion criteria were randomly assigned to receive IV fentanyl 2 mcg/kg or topical lignocaine spray 40 mg, prior to anesthesia induction with IV propofol (2-2.5 mg/kg). ProSeal™ LMA insertion condition was regarded optimal in the absence of adverse responses (gag, cough, laryngospasm and body movements), and successful LMA placement at the first attempt. Hemodynamic parameters were recorded and patients were assessed for sore throat and hoarseness post operatively. Seventy patients were analyzed. The number of patients with optimal PLMA insertion conditions were comparable between the groups (60% vs. 57%, P = 0.808). All hemodynamic parameters were comparable between groups with the exception of heart rate. Sympathetic obtundation of heart rate was greater with IV fentanyl than topical lignocaine (P < 0.05). The proportion of patients with postoperative sore throat significantly increased with the number of insertion attempts (P < 0.05). Topical lignocaine spray to the pharynx is as effective, and may be an alternative to IV fentanyl, during propofol induction for PLMA insertion. Success rate and optimal insertion condition at the first attempt, propofol requirement, blood pressure, adverse events and airway complications were comparable. Heart rate obtundation was less with topical lignocaine spray but remained within clinically acceptable values.

A Randomized Controlled Trial Comparing Wide-Awake Local Anesthesia With No Tourniquet (WALANT) to General Anesthesia in Plating of Distal Radius Fractures With Pain and Anxiety Level Perception.

INTRODUCTION: Distal end radius fractures are common fractures commonly treated with an option of open reduction and plating. Traditionally, plating is performed under general anesthesia (GA) or regional block. Recently, a new technique of plating under wide-awake local anesthesia with no tourniquet (WALANT) has been introduced. We aim to compare the preoperative anxiety level, intraoperative pain scores, post-operative pain scores, operating time, blood loss and clinical outcome of distal end radius plating with WALANT versus GA with tourniquet. METHODS: We conducted a randomized controlled study on patients with closed fracture of the distal end of the radius requiring open reduction and plating from January 2019 till April 2020. We recruited 65 patients (33 patients in the WALANT group and 32 patients in the GA group). Randomization was done via block randomization. Data were collected to evaluate preoperative anxiety using the Amsterdam Preoperative Anxiety and Information Scale (APAIS) score, intraoperative pain score during injection (baseline) (V1), 10 minutes after injection (V2), during incision (V3), during gentle manipulation (V4), during aggressive manipulation (V5) and during first drilling of screw (V6), blood loss, duration of surgery and post-operative pain score. Additionally, intraoperative visual analog scale (VAS) score was obtained in the WALANT group. At three weeks, six weeks, three months and six months after operation, the Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) scores and range of motion (ROM) of the wrists were obtained. RESULTS: The average age in the WALANT group was 47.19 (range, 36-64) years and GA group was 49.48 (range, 38-60) years. The mean APAIS score obtained was 7.78 (WALANT group) and 7.36 (GA group) with no statistical difference. For intraoperative VAS, only during V4 and V5 were the scores 1/10; otherwise at all other phases, the VAS score was 0. The average time for surgery was statistically longer in the WALANT group (61.22 minutes) compared to the GA group (55.33 minutes) (p = 0.003). There was no statistical difference in mean blood loss in both groups. The average post-operative VAS showed statistical significance only at 1 hour and 12 hours post-operation with no statistical difference at 2 and 24 hours post-operation. There was no difference in the post-operative ROM including wrist flexion, extension, supination and pronation for both groups up to six months' follow-up. CONCLUSION: There was no statistically significant difference in terms of preoperative anxiety level, intraoperative and post-operative VAS score, amount of blood loss and clinical outcome in both groups for plating of the distal end radius. However, the operating time was slightly longer in the WALANT group. We conclude that distal radius plating under WALANT has similar outcomes to GA. In centres with limited resources, WALANT offers a safe, reliable and cheaper option, reserving GA time for head, abdominal and thoracic surgery.

Normal saline versus balanced-salt solution as intravenous fluid therapy during neurosurgery: effects on acid-base balance and electrolytes.

BACKGROUND: This prospective, randomized controlled study compared the changes in acid-base balance and serum electrolytes with the use of intravenous balanced and non-balanced crystalloid solutions intraoperatively during elective neurosurgery. METHODS: Thirty consented adult patients who underwent craniotomy were randomly allocated into two groups of 15 patients each. The non-balanced group received 0.9% normal saline while the balanced group received Sterofundin®ISO as the intraoperative fluid for maintenance. Biochemical indices for acid-base balance and serum electrolytes were analyzed periodically. RESULTS: In the non-balanced group, significant changes were noted in the pH, base excess and bicarbonate values over time compared to its respective baseline values (P<0.01). Four patients (27.7%) also developed a pH<7.35 and 5 patients (33.3%) developed marked acidosis with base excess <-4.0 at the end of surgery. Both mean sodium and chloride levels were also significantly higher compared to its baseline values respectively (142.6±2.4 versus 138±2.7 mmol/L, P<0.01 and 105.7±4.1 versus 113.2±3.0 mmol/L (P<0.01). CONCLUSIONS: A balanced solution (Sterofundin®ISO) provided significantly better control over acid-base balance, sodium and chloride levels when used as intraoperative fluid maintenance and replacement during elective neurosurgery.

Comparing insertion characteristics on nasogastric tube placement by using GlideScopeTM visualization vs. MacIntosh laryngoscope assistance in anaesthetized and intubated patients / Comparação das características de inserção de sonda nasogástrica, usando visibilização pelo laringoscópio GlideScope® vs. guiada pelo laringoscópio MacIntosh em pacientes anestesiados e intubados

Abstract Background and objective: This was a prospective, randomized clinical study to compare the success rate of nasogastric tube insertion by using GlideScopeTM visualization versus direct MacIntosh laryngoscope assistance in anesthetized and intubated patients. Methods: Ninety-six ASA I or II patients, aged 18-70 years were recruited and randomized into two groups using either technique. The time taken from insertion of the nasogastric tube from the nostril until the calculated length of tube had been inserted was recorded. The success rate of nasogastric tube insertion was evaluated in terms of successful insertion in the first attempt. Complications associated with the insertion techniques were recorded. Results: The results showed success rates of 74.5% in the GlideScopeTM Group as compared to 58.3% in the MacIntosh Group (p = 0.10). For the failed attempts, the nasogastric tube was successfully inserted in all cases using rescue techniques. The duration taken in the first attempt for both techniques was not statistically significant; Group A was 17.2 ± 9.3 s as compared to Group B, with a duration of 18.9 ± 13.0 s (p = 0.57). A total of 33 patients developed complications during insertion of the nasogastric tube, 39.4% in Group A and 60.6% in Group B (p = 0.15). The most common complications, which occurred, were coiling, followed by bleeding and kinking. Conclusion: This study showed that using the GlideScopeTM to facilitate nasogastric tube insertion was comparable to the use of the MacIntosh laryngoscope in terms of successful rate of insertion and complications.

Resumo Justificativa e objetivo: Este foi um estudo clínico prospectivo e randômico para comparar a taxa de sucesso da inserção de sonda nasogástrica (NG) com as técnicas de visibilização guiada pelo laringoscópio GlideScope® versus guiada pelo laringoscópio MacIntosh em pacientes anestesiados e intubados. Métodos: Foram recrutados 96, ASA I ou II, entre 18-70 anos, e divididos randomicamente em dois grupos, com uma ou outra técnica. Foi calculado o tempo transcorrido desde a inserção da sonda NG, da narina até a inserção do comprimento calculado da sonda. A taxa de sucesso de inserção da sonda NG foi avaliada quanto à inserção bem-sucedida na primeira tentativa. As complicações associadas às técnicas de inserção foram registradas. Resultados: Os resultados mostraram taxas de sucesso de 74,5% para o grupo GlideScope® em comparação com 58,3% para o grupo MacIntosh (p = 0,10). Para as tentativas que falharam, a sonda NG foi inserida com sucesso em todos os casos, com as técnicas de resgate. A duração da primeira tentativa para ambas as técnicas não foi estatisticamente significativa: 17,2 ± 9,3 segundos no Grupo A e 18,9 ± 13,0 segundos no Grupo B (p = 0,57). No total, 33 pacientes desenvolveram complicações durante a inserção da sonda NG: 39,4% no Grupo A e 60,6% no Grupo B (p = 0,15). As complicações mais comuns ocorridas foram enrolamento, seguido de sangramento e dobradura. Conclusão: Este estudo mostrou que o uso do GlideScope® para facilitar a inserção de sonda nasogástrica foi comparável ao uso do laringoscópio MacIntosh quanto à taxa de sucesso de inserção e às complicações.

Comparing insertion characteristics on nasogastric tube placement by using GlideScope™ visualization vs. MacIntosh laryngoscope assistance in anaesthetized and intubated patients.

BACKGROUND AND OBJECTIVE: This was a prospective, randomized clinical study to compare the success rate of nasogastric tube insertion by using GlideScope™ visualization versus direct MacIntosh laryngoscope assistance in anesthetized and intubated patients. METHODS: Ninety-six ASA I or II patients, aged 18-70 years were recruited and randomized into two groups using either technique. The time taken from insertion of the nasogastric tube from the nostril until the calculated length of tube had been inserted was recorded. The success rate of nasogastric tube insertion was evaluated in terms of successful insertion in the first attempt. Complications associated with the insertion techniques were recorded. RESULTS: The results showed success rates of 74.5% in the GlideScope™ Group as compared to 58.3% in the MacIntosh Group (p=0.10). For the failed attempts, the nasogastric tube was successfully inserted in all cases using rescue techniques. The duration taken in the first attempt for both techniques was not statistically significant; Group A was 17.2±9.3s as compared to Group B, with a duration of 18.9±13.0s (p=0.57). A total of 33 patients developed complications during insertion of the nasogastric tube, 39.4% in Group A and 60.6% in Group B (p=0.15). The most common complications, which occurred, were coiling, followed by bleeding and kinking. CONCLUSION: This study showed that using the GlideScope™ to facilitate nasogastric tube insertion was comparable to the use of the MacIntosh laryngoscope in terms of successful rate of insertion and complications.

Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer.

Expression of matrix metalloproteinase 9 (MMP9) is elevated in a variety of inflammatory and oncology indications, including ulcerative colitis and colorectal cancer. MMP9 is a downstream effector and an upstream mediator of pathways involved in growth and inflammation, and has long been viewed as a promising therapeutic target. However, previous efforts to target matrix metalloproteinases (MMPs), including MMP9, have utilized broad-spectrum or semi-selective inhibitors. While some of these drugs showed signs of efficacy in patients, all MMP-targeted inhibitors have been hampered by dose-limiting toxicity or insufficient clinical benefit, likely due to their lack of specificity. Here, we show that selective inhibition of MMP9 did not induce musculoskeletal syndrome (a characteristic toxicity of pan-MMP inhibitors) in a rat model, but did reduce disease severity in a dextran sodium sulfate-induced mouse model of ulcerative colitis. We also found that MMP9 inhibition decreased tumor growth and metastases incidence in a surgical orthotopic xenograft model of colorectal carcinoma, and that inhibition of either tumor- or stroma-derived MMP9 was sufficient to reduce primary tumor growth. Collectively, these data suggest that selective MMP9 inhibition is a promising therapeutic strategy for treatment of inflammatory and oncology indications in which MMP9 is upregulated and is associated with disease pathology, such as ulcerative colitis and colorectal cancer. In addition, we report the development of a potent and highly selective allosteric MMP9 inhibitor, the humanized monoclonal antibody GS-5745, which can be used to evaluate the therapeutic potential of MMP9 inhibition in patients.

R723, a selective JAK2 inhibitor, effectively treats JAK2V617F-induced murine myeloproliferative neoplasm.

The activating mutations in JAK2 (including JAK2V617F) that have been described in patients with myeloproliferative neoplasms (MPNs) are linked directly to MPN pathogenesis. We developed R723, an orally bioavailable small molecule that inhibits JAK2 activity in vitro by 50% at a concentration of 2nM, while having minimal effects on JAK3, TYK2, and JAK1 activity. R723 inhibited cytokine-independent CFU-E growth and constitutive activation of STAT5 in primary hematopoietic cells expressing JAK2V617F. In an anemia mouse model induced by phenylhydrazine, R723 inhibited erythropoiesis. In a leukemia mouse model using Ba/F3 cells expressing JAK2V617F, R723 treatment prolonged survival and decreased tumor burden. In V617F-transgenic mice that closely mimic human primary myelofibrosis, R723 treatment improved survival, hepatosplenomegaly, leukocytosis, and thrombocytosis. R723 preferentially targeted the JAK2-dependent pathway rather than the JAK1- and JAK3-dependent pathways in vivo, and its effects on T and B lymphocytes were mild compared with its effects on myeloid cells. Our preclinical data indicate that R723 has a favorable safety profile and the potential to become an efficacious treatment for patients with JAK2V617F-positive MPNs.

Interferometric enhancement of x-ray reflectivity from unperturbed Langmuir monolayers of amphiphiles at the liquid-gas interface.

Langmuir monolayers provide an important system for the investigation of the intramolecular structure and intermolecular ordering of organic and bio-organic macromolecular amphiphiles at an interface between polar and nonpolar media, e.g., the liquid-gas interface. Specular x-ray and neutron reflectivity have contributed substantially to these investigations. However, these reflectivity techniques are generally limited by the absence of crucial phase information, the relatively small contribution of the amphiphile to the scattering-length density contrast across the interface, and the relatively limited range of momentum transfer available perpendicular to the interface. Although several procedures have been developed to provide model-independent solutions to the phase problem, there remains a limited ability to distinguish features of slightly differing contrast (i.e., the "sensitivity") as well as their minimum allowable separation (i.e., the "spatial resolution") along the length of the scattering-length density profile derived from the reflectivity data via solution to the phase problem. Here, we demonstrate how the well-known interferometric approach can be extended to the structural investigation of otherwise unperturbed Langmuir monolayers of these amphiphiles to provide a direct solution to the phase problem and importantly, substantially enhance both the sensitivity and the spatial resolution in the derived profiles.