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Background: Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT., Methods: We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité-Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO 2 -adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment., Results: From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO 2 -adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group (p = 0.26)., Conclusion: Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS., Trial Registration: The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed., (© 2024. The Author(s).)

Yin chai hu (Radix Stellariae) is a root medicine that is frequently used in Chinese traditional medicine to treat fever and malnutrition. In modern medicine, it has been discovered to have anti-inflammatory, anti-allergic, and anticancer properties. In a previous study, we were able to extract lipids from Stellariae Radix using supercritical CO 2 extraction (SRE), and these sterol lipids accounted for up to 88.29% of the extract. However, the impact of SRE on the development of atopic dermatitis (AD) has not yet been investigated. This study investigates the inhibitory effects of SRE on AD development using a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Treatment with SRE significantly reduced the dermatitis score and histopathological changes compared with the DNCB group. The study found that treatment with SRE resulted in a decrease of pro-inflammatory cytokines TNF-α, CXC-10, IL-12, and IL-1β in skin lesions. Additionally, immunohistochemical analysis revealed that SRE effectively suppressed M1 macrophage infiltration into the AD lesion. Furthermore, the anti-inflammatory effect of SRE was evaluated in LPS + INF-γ induced bone marrow-derived macrophages (BMDMs) M1 polarization, SRE inhibited the production of TNF-α, CXC-10, IL-12, and IL-1β and decreased the expression of NLRP3. Additionally, SRE was found to increase p-AMPK T172 , but had no effect on total AMPK expression, after administration of the AMPK inhibitor Compound C, the inhibitory effect of SRE on M1 macrophages was partially reversed. The results indicate that SRE has an inhibitory effect on AD, making it a potential therapeutic agent for this atopic disorder., (© 2024 Wiley Periodicals LLC.)

The recent evidence regarding the effectiveness of renal denervation (RDN) in blood pressure control is becoming increasingly substantial. However, many studies have excluded populations with severely impaired kidney function, even though these individuals have a higher prevalence of hypertension compared to the general population, and controlling their blood pressure is more challenging. The effectiveness and safety of RDN in patients with severe chronic kidney disease (CKD) lack strong evidence support. Concerns about worsening kidney function still exist, particularly in patients with CKD stage 5. We conducted an observational study involving 10 patients who were using at least 3 different antihypertensive medications and had an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m 2 but had not undergone dialysis. For these patients, we performed RDN via the radial artery approach, with the assistance of carbon dioxide (CO 2 ) angiography. Utilizing this approach, the systolic 24-hour ambulatory blood pressure monitoring did not exhibit a significant decrease at 3 months; however, a significant reduction was observed at 6 months after RDN. We also minimized contrast agent usage, observed no kidney function decline 3 months post-RDN, and experienced no vascular-related complications. Using the radial artery approach and CO 2 angiography assistance for RDN may be an effective and safe blood pressure control method for patients with severe kidney impairment., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Several treatment modalities are available for the treatment of vitiligo due to the lack of a uniformly effective therapy. Topical latanoprost 0.005% is an effective topical treatment. Fractional CO 2 laser alone or combined with platelet-rich plasma (PRP) has been proposed as effective adjunctive therapies., Objectives: We aimed to compare the efficacy of topical latanoprost 0.005% (Ioprost®, Orchidia, Egypt) combined with either add-on fractional CO 2 laser or fractional CO 2 -PRP versus topical latanoprost monotherapy in the treatment of localized stable vitiligo., Patients/methods: The study included 60 patients randomly assigned into three equal groups. Group A patients received topical latanoprost drops only. Group B patients received topical latanoprost drops and fractional CO 2 laser sessions at 2-week interval for 3 months. Group C patients received topical latanoprost drops and fractional CO 2 laser sessions combined with PRP at a 2-week interval for 3 months. The mean improvement score by the physician was calculated 4 months after the start of the study. Punch skin biopsies were obtained before treatment and 4 months from the beginning of the study and stained with H&E and HMB-45 antibody for evaluation of pigmentation., Results: Significant clinical improvement of vitiligo lesions with significant increase of re-pigmentation were reported in the three treated groups. Latanoprost in combination with fractional CO 2 and PRP was associated with more significant therapeutic outcomes than either combined latanoprost and fractional CO 2 or latanoprost alone., Conclusion: Fractional CO 2 laser-PRP enhances the therapeutic efficacy of latanoprost 0.005% in the treatment of localized stable vitiligo., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: This in situ study aimed to investigate the efficacy of CO 2 laser at a 10.6-µm wavelength combined with 1.23% acidulated phosphate fluoride (APF) and fluoridated dentifrice with 1100 µg F/g (FD) to control enamel caries progression., Materials and Methods: Sixteen volunteers wore palatal appliances containing eight demineralized enamel specimens for four 14-day phases under sucrose exposure. These specimens were submitted to CO 2 laser irradiation and APF alone or combined with FD. Treatment groups were non-fluoridated dentifrice-NFD, NFD + CO 2 laser, NFD + APF, NFD + CO 2 laser + APF, FD, FD + CO 2 laser, FD + APF, and FD + CO 2 laser + APF. Mineral loss, calcium fluoride (CaF 2 ), fluorapatite (FAp), and fluoride in the biofilm were analyzed by analysis of variance followed by the Student-Newman-Keuls test, p < 0.05., Results: The highest mineral loss inhibition was noted when FD and CO 2 laser irradiation were combined, which did not significantly differ from the FD + CO 2 laser + APF group. The CaF 2 , FAp, and F in the biofilm were more pronounced when the FD and APF were combined. The CO 2 laser irradiation promoted a slightly higher concentration of CaF 2 in the enamel and F in the biofilm., Conclusion: Although APF promotes the high formation of CaF 2 and FAp, the combined use of FD with CO 2 laser overcomes the APF effect in inhibiting the progression of artificial caries-like lesions in situ., Clinical Significance: Under the in situ design of this study, remineralization of white spot lesions was achieved through CO 2 laser irradiation and daily use of fluoridated dentifrice. Future clinical trials are encouraged to substantiate this finding., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Acetazolamide has been used for diuretic-induced metabolic alkalosis, but the preferred dose, route, and frequency of administration remain unknown., Objective: The purpose of this study was to characterize dosing strategies and determine the effectiveness of intravenous (IV) and oral (PO) acetazolamide for patients with heart failure (HF) with diuretic-induced metabolic alkalosis., Methods: This was a multicenter, retrospective cohort study comparing the use of IV versus PO acetazolamide in patients with HF receiving at least 120 mg of furosemide for the treatment of metabolic alkalosis (serum bicarbonate CO 2 ≥32). The primary outcome was the change in CO 2 on the first basic metabolic panel (BMP) within 24 hours of the first dose of acetazolamide. Secondary outcomes included laboratory outcomes, such as change in bicarbonate, chloride, and incidence of hyponatremia and hypokalemia. This study was approved by the local institutional review board., Results: IV acetazolamide was given in 35 patients and PO acetazolamide was given in 35 patients. Patients in both groups were given a median of 500 mg of acetazolamide in the first 24 hours. For the primary outcome, there was a significant decrease in CO 2 on the first BMP within 24 hours after patients received the IV acetazolamide (-2 [interquartile range, IQR: -2, 0] vs 0 [IQR: -3, 1], P = 0.047). There were no differences in secondary outcomes., Conclusion and Relevance: IV acetazolamide resulted in significantly decreased bicarbonate within 24 hours of administration. IV acetazolamide may be preferred to treat diuretic-induced metabolic alkalosis in patients with HF., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: Few treatments are available in the subacute phase of traumatic brain injury (TBI) except rehabilitation training. We previously reported that transient CO 2 inhalation applied within minutes after reperfusion has neuroprotective effects against cerebral ischemia/reperfusion injury. In this study, it was hypothesized that delayed CO 2 postconditioning (DCPC) starting at the subacute phase may promote neurological recovery of TBI., Methods: Using a cryogenic TBI (cTBI) model, mice received DCPC daily by inhaling 5%/10%/20% CO 2 for various time-courses (one/two/three cycles of 10-min inhalation/10-min break) at Days 3-7, 3-14 or 7-18 after cTBI. Beam walking and gait tests were used to assess the effect of DCPC. Lesion size, expression of GAP-43 and synaptophysin, amoeboid microglia number and glia scar area were detected. Transcriptome and recombinant interferon regulatory factor 7 (Irf7) adeno-associated virus were applied to investigate the molecular mechanisms., Results: DCPC significantly promoted recovery of motor function in a concentration and time-course dependent manner with a wide therapeutic time window of at least 7 days after cTBI. The beneficial effects of DCPC were blocked by intracerebroventricular injection of NaHCO 3 . DCPC also increased puncta density of GAP-43 and synaptophysin, and reduced amoeboid microglia number and glial scar formation in the cortex surrounding the lesion. Transcriptome analysis showed many inflammation-related genes and pathways were altered by DCPC, and Irf7 was a hub gene, while overexpression of IRF7 blocked the motor function improvement of DCPC., Conclusions: We first showed that DCPC promoted functional recovery and brain tissue repair, which opens a new therapeutic time window of postconditioning for TBI. Inhibition of IRF7 is a key molecular mechanism for the beneficial effects of DCPC, and IRF7 may be a potential therapeutic target for rehabilitation after TBI., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The digestive system is exposed to severe inflammation as a result of taking some medications that have gastrointestinal side effects. Sixty Swiss-albino male mice were randomly distributed into six groups to treat inflammations of the colon, stomach, and small intestine caused by taking high doses of diclofenac (D), with two novel synthesized compounds, pyrazolo [3,4 d] pyridazine derivatives (Co1 and Co2). Myeloperoxidase enzyme activity was determined in the colon and small intestinal tissues. Serum contents of TNF-α, IL-22, IgG, and IgM were determined by ELISA. Histopathological examinations of the colon, small intestinal, and stomach tissues were microscopically analyzed. TNF-α, IL-22, and TNFSF11 gene expression were measured in the colon, intestinal, and spleen using qRT-PCR. Diclofenac caused surface columnar epithelial cell loss, focal necrosis of the gastric mucosa, inflammatory cell infiltration, and congested blood vessels in the stomach, colon, and small intestinal tissues. Co1 component was found to be better than Co2 component in reducing the focal necrosis of gastric mucosa and improving the histological structures of the stomach, colon, and small intestinal tissues. After 14 days, the activity of the myeloperoxidase enzyme was increased in group D and decreased in groups DCo1, DCo2, Co1, and Co2. Serum concentrations of TNF-α and IgG were increased, while IL-22 and IGM were reduced in the D, DCo1, and DCo2 groups compared with the Co1 and control groups. TNF-α gene was upregulated in the D group and downregulated in the Co1 group, while the IL-22 gene was downregulated in the D group and upregulated in the Co1 group compared with the control group. The CO1 component may be useful in reducing digestive system inflammation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Photodynamic therapy (PDT) for actinic keratosis (AK) is limited by the depth of treatment. Microneedling or fractional CO 2 laser can facilitate the penetration of photosensitizer, while cryotherapy can treat deeper tissues but is not suitable for field cancerization., Objective: To investigate the efficacy of microneedling, fractional CO 2 laser, and cryotherapy in combination with PDT for AK., Methods: Patients with AK were randomized into 4 groups, including group A with microneedling + PDT, group B with fractional CO 2 laser + PDT, group C with cryotherapy + PDT, and group D with PDT. After 12 weeks, the clinical, dermoscopic, and reflectance confocal microscopy (RCM) outcomes were assessed., Results: A total of 129 patients were included in this study, with 31, 30, 35, and 31 patients in each group, yielding clinical response rates of 90.3%, 93.3%, 97.1%, and 74.2%, respectively (P=0.026). The RCM response rates were 71.0%, 80.0%, 85.7%, and 54.8%, respectively (P=0.030). The dermoscopic response rates were 77.4%, 83.3%, 88.6%, and 60.0%, respectively (P=0.039). Group C showed the best efficacy in terms of clinical, dermoscopic, and RCM outcomes., Conclusions: All three treatments improved the efficacy of PDT and were well tolerated, with cryotherapy + PDT showing the best efficacy., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier B.V.)

Background: Carboxytherapy is defined as intradermal and/or subcutaneous microinjections of sterile purified carbon dioxide into different parts of the body for therapeutic aims. The vasodilatation effect and intradermal collagen reorganization associated with carboxytherapy have advantages for aesthetic dermatology and cosmetology., Objective: In the current article, we have reviewed some of the most important indications of this modality in dermatology and aesthetic dermatology., Method: Our review is a narrative one which has gathered some of the most important indications of carboxytherapy in dermatology and cosmetology., Results: Carboxytherapy has successfully been applied for some dermatologic and cosmetic conditions among which skin aging, cellulite, localized fat deposits, striae distensae, infraorbital hyperpigmentation, scar, lymphedema, androgenetic alopecia, alopecia areata, psoriasis, morphea, and vitiligo are the most important., Conclusion: Carboxytherapy can be considered as a safe, minimally-invasive modality used for rejuvenation, restoration, and recondition of the skin., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objective: To evaluate the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) and CO 2 laser therapy of low-grade vaginal intraepithelial neoplasia (VAIN1) combined with high-risk human papillomavirus (hr-HPV) infection., Methods: A total of 163 patients with VAIN1 and hr-HPV infection were divided into PDT Group (n = 83) and CO 2 laser Group (n = 80). The PDT Group received six times of ALA-PDT treatments and the CO 2 laser Group received once CO 2 laser treatment. HPV types, cytology, colposcopy, and pathological examinations were carried out before and after treatment. The differences in HPV clearance rate, VAIN1 regression rate, and adverse reactions between the two groups were analyzed during 6-month follow-up., Results: The overall HPV clearance rate of the PDT Group was significantly higher than that of the CO 2 laser Group (65.06% vs 38.75%, P = 0.0008) although similar result was obtained for 16/18-related HPV infection patients (54.55% vs 43.48%, P = 0.4578). The VAIN1 regression rate of the PDT Group was significantly higher than that of the CO 2 laser Group (95.18% vs 83.75%, P = 0.0170). In patients ≥ 50 years old, ALA-PDT showed better HPV clearance rate and VAIN1 regression rate than CO 2 laser therapy (P < 0.05). The adverse reactions in the PDT Group were significantly lower than that in the CO 2 laser Group (P > 0.05)., Conclusions: The efficacy of ALA-PDT appears better than CO 2 laser for VAIN1 patients. However, the long-term effect of ALA-PDT for VAIN1 still needs to be explored. As a non-invasive treatment, ALA-PDT is a highly effective therapeutic procedure for VAIN1 with hr-HPV infection., Competing Interests: Declaration of Competing Interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To investigate the clinical outcomes of morphology-guided surgical treatment for adult laryngeal and hypopharyngeal hemangioma., Materials and Methods: Patients diagnosed with adult laryngeal and hypopharyngeal hemangioma by outpatient laryngoscopy and received surgical treatments were retrospectively included. Size and morphology were classified to guide the choose of surgical procedures including CO 2 laser excision, CO 2 coagulation + bleomycin injection and potassium-titanyl-phosphate (KTP) laser + bleomycin injection. The baseline information and pre-, postoperative laryngoscopies were collected, the outcomes were followed up and analyzed., Results: A total of 68 patients were included, 7 cases with exophytic and non-bulky hemangioma received CO 2 laser excision, 20 cases received CO 2 laser coagulation + bleomycin injection and 25 cases with KTP + bleomycin injection, another 16 cases with pure bleomycin injection were included as comparison. There was no difference of baseline analysis among the groups (P >  = 0.05). Positive outcomes were achieved in most cases of CO 2 excision (100%), CO 2 coagulation + bleomycin (90.0%) and KTP + bleomycin (84.0%) groups, which were better than pure bleomycin (56.3%, p = 0.001). CO2 or KTP, associated to Bleomycin, gave same results on same lesions (P = 0.132)., Conclusions and Significance: Morphology of hemangioma may help in the selection of surgical procedures. CO 2 coagulation can be used as a potential substitute for KTP in the treatment of adult laryngeal and hypopharyngeal hemangioma., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Fractional carbon dioxide (CO 2 ) laser resurfacing is used successfully for facial rejuvenation. Post procedure skincare is a variable that influences downtime caused by pain/tenderness, erythema, crusting, and bruising., Aims: The primary objective of this pilot study was to demonstrate the benefits of human platelet extract (HPE) (plated)™ CALM Serum, a new topical cosmetic product, following fractionated CO 2 ablative laser resurfacing treatment to the entire face versus standard of care., Methods: In a single-center, randomized, evaluator-blinded pilot study, a total of 18 subjects were randomized into two groups, CO 2 facial resurfacing followed by post-procedural standard of care (Stratacel silicone gel) or CO 2 facial resurfacing with the addition of HPE renewosomes in the CALM Serum., Results: CALM Serum demonstrated statistically significant less crusting at Day 10 compared to the control group (p = 0.0193) with less downtime in the first 14 days (p = 0.03). Subjects treated with CALM Serum had statistically significant brighter appearing skin at 14 days (p = 0.007) and more youthful looking skin on Days 14 and 30 (p = 0.003 and 0.04, respectively)., Conclusions: This study demonstrates that Renewosome™ technology provides statistically significant post-laser clinical recovery over silicone gel for reducing crusting, and downtime. Subjects reported less diary days of symptoms of pain/tenderness, redness, crusting/flaking, bruising, and itching in the first 14 days compared to the control group. CALM also demonstrated statistically significant improvements in brighter and more youthful appearing skin. CALM is safe and well tolerated., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Postmenopausal vaginal symptoms affect over 60% of women and may substantially impact a woman's quality of life. Since 2012, fractional CO 2 laser has been suggested as a treatment for this indication. Structural assessment of vaginal epithelium using microscopic biopsy examination has been used as a primary outcome measure and surrogate determinant of success of vaginal laser in previous clinical studies., Objective: This study aimed to report the effects of laser compared with sham treatment on human vaginal epithelium from postmenopausal women using microscopic examination of tissue biopsies., Study Design: This single-center double-blind, sham-controlled randomized controlled trial was performed in a tertiary hospital in Sydney, Australia. A total of 49 postmenopausal women who were symptomatic of at least 1 vaginal symptom (vaginal dryness, burning, itching; dyspareunia; or dryness) were randomized to either laser or sham treatment. For this nested histologic study, participants had a pre- and post-treatment vaginal wall biopsy collected. Biopsy samples were analyzed by 3 independent specialist gynecologic pathologists and categorized as Type 1 (well-estrogenized), 2 (poorly estrogenized), or 3 (combination) mucosae. Other outcomes assessed included symptom severity (visual analog scale for symptoms including most bothersome symptom, and Vulvovaginal Symptom Questionnaire) and Vaginal Health Index. Prespecified secondary analyses of data were performed. Categorical data were analyzed using the Pearson chi-square test (or Fisher exact test if <5 in any category) or related-samples McNemar test for paired nonparametric data. Nonparametric, continuous variables were assessed using Wilcoxon signed-rank test or Mann-Whitney U test, and parametric variables with t test or 1-way analysis of variance as appropriate. All analyses were performed using SPSS software version 26.0 (IBM Corp, Armonk, NY)., Results: There was no significant difference in microscopic features of vaginal epithelium following laser or sham treatment (P=.20). Further subgroup analyses of age, menopause type, duration of reproductive life, time since menopause and BMI, still demonstrated no significant difference between laser and sham groups in histological category of vaginal epithelium. Microscopic features at pre-treatment vaginal biopsy were Type 1 in 27% (13/49). There was no significant difference in VAS score for overall vaginal symptom between those classified as Type 1 vs. Type 2/3 (VAS score overall: Type 1 vs. Type 2/3, (48.1 [95% CI 27.0, 69.2] vs. 61.5 [95% CI 49.8, 73.3]; P=.166)., Conclusion: Data from this double-blind, sham-controlled randomized controlled trial demonstrate that fractional CO 2 laser and sham treatment have a comparable histologic effect on vaginal tissue that is not significantly different. Fractional CO 2 laser is not significantly different from sham treatment and should not be recommended for clinical use for postmenopausal vaginal symptoms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Treating nail psoriasis is often a time-consuming challenge with an unsecure outcome. Response to the treatment is variable and relapses are common. Systemic treatments have multiple systemic side effects and lack of the patient compliance makes intra-lesional therapies not the best choice for treatment of nail psoriasis. We aimed to evaluate and compare the efficacy and side effects of methotrexate versus calcipotriol plus betamethasone two-compound formula when applied topically to psoriatic nails after fractional CO 2 laser. This comparative pilot study included 20 patients with nail psoriasis. One side was treated with fractional CO 2 laser followed by the application of topical methotrexate (Group A) and the other side with fractional CO 2 laser followed by topical (Calcipotriol 0.05 mg/gm + Betamethasone 0.5 mg/gm) (Group B). 4 sessions were done, once every 2 weeks. There was a high statistical significant decrease in total NAPSI score in group A at 1(P = 0.000) and 2 months (P = 0.000). There was a high statistical significant decrease in total NAPSI score in group B at 1(P = 0.001) and 2 months (P = 0.001). There was no statistical significant difference regarding total NAPSI score between both group A and B at 0 (P = 0.271), 1(P = 0.513) and 2 months (P = 0.647). Combined fractional CO 2 laser with either topical MTX or topical betamethasone plus calcipotriol two-compound formula is effective treatment for nail psoriasis., (© 2023. The Author(s).)

Background: Pressurized metered-dose inhalers (pMDIs) exert an environmental impact resulting from CO2 emissions. Therapeutic alternatives with less environmental impact are widely used. Nevertheless, the choice of device and appropriate therapy should meet the clinical needs and the characteristics of the patient., Objective: The primary objective was to estimate the impact of pMDIs prescribed for any indication on annual CO2 emissions in Spain.The secondary objective was to evaluate the potential impact of switching pMDIs to dry-powder inhalers (DPIs) in patients with asthma., Methods: A systematic review of the evidence published during 2010-2021 was carried out. Average annual CO2 emissions of DPIs and pMDIs were calculated in 2 scenarios: the current situation and a hypothetical situation involving a switch from all pMDIs to DPIs. The impact of the switch on clinical outcomes was also evaluated., Results: The total value of CO2-eq/year due to DPIs and pMDIs accounted for 0.0056% and 0.0909%, respectively, of total emissions in Spain. In the event of switching pMDIs to DPIs, except those used for rescue medication, the percentages were 0.0076% and 0.0579%. The evaluation of efficacy, handling, satisfaction, safety, and use of health care resources was not conclusive., Conclusions: Current CO2 emissions by pMDIs account for a small percentage of the total CO2 footprint in Spain. Nevertheless, there is a need for research into new and more sustainable devices. Suitability and patient clinical criteria such as age and inspiratory flow should be prioritized when prescribing an inhaler.

Background: Cerebral microvascular dysfunction is commonly seen in Alzheimer's disease (AD) and vascular cognitive impairment (VCI). Cerebrovascular reactivity (CVR) to CO 2 reflects cerebral microvascular health and may be modulated by the renin-angiotensin system (RAS). This study aimed to investigate the effects of RAS modulation on CVR in individuals with mild cognitive impairment (MCI) due to underlying vascular or AD etiologies., Methods: This study presents findings of candesartan's effects on the secondary outcomes of two double-blind randomized clinical trials of 12-month therapy of candesartan versus lisinopril in VCI (CALIBREX (Candesartan vs Lisinopril Effects on the Brain and Endothelial Function in Executive MCI)) and candesartan versus placebo in prodromal AD (Candesartan's Effects on Alzheimer's Disease and Related Biomarkers (CEDAR)). Primary outcome results of these trials have been reported in previous publications. Participants underwent identical brain blood oxygenation level dependent (BOLD)-CVR in response to a 2-min CO 2 challenge at baseline and 12 months. Regions of interest and voxel-wise CVR maps were derived from BOLD signal changes during CO 2 challenge. CVR effects were compared between candesartan and lisinopril (CALIBREX) and candesartan and placebo (CEDAR) using mixed-model repeated measures., Results: Data from 102 participants in the CALIBREX study (mean age = 65 years, 45% female, 63% African American) and 59 in the CEDAR study (mean age = 67 years, 32% female, 20% African American) were analyzed. Candesartan was associated with improved whole brain CVR compared to placebo in the CEDAR study (adjusted within-group mean difference for candesartan = 0.27 (95% confidence interval (CI) = 0.006, 0.53) vs placebo = -0.17 (95% CI = 0.42, 0.08), p-value = 0.018), and compared to lisinopril in the CALIBREX study (adjusted within-group mean difference for candesartan = 0.28 (95% CI = 0.10, 0.46) vs lisinopril = -0.08 (95% CI = -0.31, 0.14), p-value = 0.012), independent of blood pressure. In an exploratory meta-analysis of the two trials, improved CVR in the hippocampus was linked to improved attention and working memory (p = 0.044) and a trend for improved executive function (p = 0.087) with candesartan therapy., Conclusion: This study suggests that candesartan is associated with improved microvascular function in MCI, and these findings are independent of its blood pressure effect in these VCI and prodromal AD populations.

Onychomycosis is a fungal infection of the nail unit caused by various species of dermatophytes, non-dermatophytic moulds or yeasts. They pose a therapeutic challenge to the treating dermatologist as the infection is often resistant to treatment and requires prolonged therapy. To evaluate the efficacy and safety profile of fractional CO 2 laser and 0.25% Amorolfine hydrochloride cream in the treatment of onychomycosis. In this randomized controlled study on 50 patients with fingernail onychomycosis, one group (25 patients, 30 nails) were treated with fractional CO 2 laser and 0.25% Amorolfine hydrochloride cream, and the second group (25 patients, 31 nails) with oral itraconazole pulse therapy. Four treatment sessions were carried out in the first group at an interval of two weeks each. Whereas, the second group received 2 doses of itraconazole pulse therapy with one month interval each. Both the groups were followed up for a period of 4 months. Results were assessed by Onychomycosis severity index(OSI), Physician global assessment scale, patient's subjective score and fungal microscopy. Complete resolution was seen in 14 out of 25(56%) patients and 6 out of 25(24%) patients in group 1 and group 2 respectively. There was statistically significant difference in the response between the two groups during 1 st and 2 nd follow up (p value - 0.004 and 0.023 respectively). Fractional CO2 laser with amorolfine cream is proved to be a better modality in onychomycosis therapy compared to oral itraconazole pulse therapy, especially in distal lateral subungual and superficial white onychomycosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Melasma is a chronic relapsing skin condition. Laser therapy is a new advancement in treatment. Whether the topical application of tranexamic acid (TXA) increases the efficacy of laser therapy in melasma is still under debate. With recent studies yielding different results, it was imperative to compile all the available literature systematically. This meta-analysis investigates the effectiveness of a combination therapy of laser plus TXA acid for treating melasma. PubMed/MEDLINE, Cochrane Central, Google Scholar, Scopus, and the International Clinical Trials registry were systematically searched for article retrieval. Screening per PRISMA guidelines was undertaken by two independent reviewers using the Covidance database. Melasma area of severity index (MASI)/modified MASI was used as the clinical improvement outcomes. A total of nine studies that described the combined use of topical tranexamic acid with laser therapy were included for meta-analysis. These studies employed various types of lasers along with topical TXA. The results showed that the combination of both laser therapy and topical TXA significantly decreased the MASI score (P < 0.0001). Subgroup analyses revealed that fractional CO 2 laser among the laser types and monthly laser plus twice daily topical TXA were most effective in decreasing the MASI/mMASI score. The meta-analysis found that combining topical tranexamic acid and laser therapy is an effective and safer treatment option for treatment-resistant melasma. Furthermore, monthly fractional CO 2 laser and daily application of topical tranexamic acid showed high effectiveness and safety., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background and Objectives : For many years, fully ablative laser treatments, particularly those performed with a carbon dioxide (CO 2 ) laser, were regarded as the gold standard for resurfacing. This study's goal is to assess the depth that can be reached by a new CO 2 scanner system, through a skin model with greater dermal thickness, to use in the treatment of deep scarring. Materials and Methods : Male human skin tissue was laser-treated using a CO 2 fractional laser and a new scanning system, and all samples were fixed in 10% neutral buffered formalin, dehydrated using a series of crescent alcohol, embedded in paraffin, sectioned in series (4-5 µm thick), stained with haematoxylin and eosin (H&E), and then analysed under an optical microscope. Results : From the epidermis through the underlying papillary and reticular dermis to various depths of the dermis, microablation columns of damage and coagulated microcolumns of collagen were observed. The reticular dermis was fully penetrated up to 6 mm at higher energy levels (210 mJ/DOT), resulting in deeper tissue injury. Although the laser might penetrate further, the skin stops there, leaving just the fat and muscular tissue. Conclusions : The deep layers of the dermis can be penetrated by the CO 2 laser system throughout the entire dermal thickness when using the new scanning system, suggesting that this laser's potential impact, at the selected settings, covers all skin targets required to perform superficial or deep treatments on any dermatological issue. Finally, patients who have problems, such as morbid scar-deep complications, which affect their quality of life, are more likely to profit from this innovative technique.

Background: Contraction alkalosis is characterized by low serum sodium and chloride and high serum carbon dioxide and bicarbonate levels. Case Report: A 28-year-old Caucasian active-duty male with a history of autosomal dominant polycystic kidney disease and diarrhea-predominant Irritable Bowel Syndrome (D-IBS) presented to his primary care provider (PCP) with elevated blood pressure (136/96 mmHg), was diagnosed with stage-2 hypertension, and started oral HCTZ (25 mg/day). His medications included dicyclomine (10 mg oral three times daily). Subsequently, (Visit 1), his blood pressure was 130/91 mmHg and he was started on telmisartan (20 mg/day). At Visit 2, 4 weeks later, his blood pressure improved (121/73 mmHg); however, blood chemistry revealed elevated serum CO2 (32 mEq/L) and chloride (94 mmol/L). Four days later, the patient presented to the Emergency Department with dyspnea and swallowing difficulty. The patient returned to his PCP 3 days later complaining of cough, congestion, vomiting, and mild dyspnea, blood pressure of 124/84 mmHg. Two months later, sudden onset of projectile vomiting and abdominal pain while running was reported, resolved by rehydration and a single oral dose of prochlorperazine 25 mg. Three months later, (Visit 3), he complained of lightheadedness and cloudy judgment, suggesting contraction alkalosis. HCTZ was discontinued and telmisartan was increased to 20 mg twice daily. A follow-up blood chemistry panel 2 weeks later revealed serum chloride and CO2 levels within normal limits and blood pressure under 130/80 mmHg. Conclusion: This is the first known report of contraction alkalosis driven by drug-drug interaction between dicyclomine and HCTZ.

We compared the therapeutic effect of catheter direct thrombolysis (CDT) and peripheral venous thrombolysis (PVT) for patients with acute pulmonary embolism (APE). Totally, 74 patients with APE were enrolled, including 37 in the CDT group and 37 in the PVT group. The changes in clinical indicators pre and posttreatment were observed. Clinical efficacy was evaluated. Kaplan-Meier method was used to analyze the survival of patients during follow-up. In both the PVT group and CDT group, partial pressure of oxygen after treatment increased significantly than that before treatment (P < .05). However, in both groups, the levels of partial pressure of carbon dioxide, D-dimer, B-type brain natriuretic peptide, pulmonary arterial pressure, and thrombus volume after treatment were significantly decreased than those before treatment (P < .05). After treatment, patients from the CDT group had significantly lower D-dimers, partial pressure of carbon dioxide, brain natriuretic peptide, and pulmonary arterial pressure, and significantly higher partial pressure of oxygen compared to patients from the PVT group (P < .05). The total effective rate was 97.2% in the CDT group and 81.0% in the PVT group. The bleeding incidence in the CDT group was significantly lower than that in the PVT group (P < .05). The median survival time in the CDT group was significantly longer than that in the PVT group (P < .05). CDT can more effectively improve symptoms, cardiac function, and survival rate of APE patients while reducing bleeding incidence than PVT, and thus is safe and effective in treating APE., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Alopecia areata (AA) is a non-scarring tissue-specific autoimmune disorder. Many therapeutic modalities are available for the treatment of AA, but none has yet proven to be uniformly effective. Fractional carbon dioxide (FRCO 2 ) laser has been introduced as a treatment modality for AA. The objective is to evaluate and compare the efficacy and safety of FRCO 2 laser in treatment of AA alone or in combination with betamethasone valerate cream. 30 patients were assigned to one of the following groups, Group A FRCO 2 , Group B FRCO 2 plus betamethasone valerate cream or Group C (betamethasone valerate cream). Patients received eight laser sessions 2 weeks apart, treatment period was 4 months. A statistically significant decrease in SALT score, dystrophic hair and a statistically significant increase in terminal hair was observed in all groups. Patient satisfaction level and reduction in SALT score were significantly higher among FRCO 2 and FRCO 2 plus betamethasone valerate group. However, no statistical significant difference was found between FRCO 2 group and FRCO 2 combined with betamethasone valerate cream group. FRCO 2 laser is a safe and effective treatment modality for AA when used alone or in combination with betamethasone valerate cream. However, it was found superior to betamethasone valerate cream monotherapy., (© 2022. The Author(s).)

Aim: In Duchenne muscular dystrophy (DMD), lung disease contributes significantly to morbidity and mortality. This study aimed to assess the usefulness of various pulmonary function tests in evaluating DMD severity., Methods: This retrospective study analysed lung function tests of patients with DMD-treated in the multidisciplinary respiratory neuromuscular clinic at Schneiders' Children Medical Center of Israel. Data were analysed according to age, ambulatory status and glucocorticoid treatment., Results: Among 90 patients with DMD, 40/63 (63.5%) ambulatory patients and 22/27 (81.5%) nonambulatory patients successfully performed spirometry. Significant annual declines were demonstrated among nonambulatory patients, in percentile predicted forced vital capacity (3.8%) and in total lung capacity (5.5%) per year. The decline correlated with age and loss of ambulation but not with steroid treatment. Peak cough flow values were randomly distributed and did not correlate with age, ambulation or treatment. In nonambulatory patients, transcutaneous carbon dioxide measurement correlated significantly with age (r = 0.55, p = 0.02)., Conclusion: Forced vital capacity, total lung capacity and transcutaneous carbon dioxide correlated with the clinical severity of disease in children with DMD. These measures may be useful in follow-up and clinical trials. A comparable correlation was not found for peak cough flow., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: Carboxytherapy involves injecting carbon dioxide in the dermal and subcutaneous layers to achieve an increase in the local microvascularization of the tissue where it is applied. Our aim is to analyze its effectiveness in the treatment of pathological scars, as well as its adverse effects., Methods: We conducted a prospective single-center study in patients under 18 years of age with atrophic and hypertrophic scars caused by surgical interventions or trauma, mainly burns. Each patient underwent two sessions, 6 weeks apart in time. Scar quality was evaluated using the Vancouver Scar Scale before the first session and 6 weeks after the second session. Adverse effects observed during the procedure and at follow-up in outpatient clinic were collected., Results: A total of 16 patients were included (5 males; 11 females), with a median age of 12.7 years (interquartile range 8.5-15.2), in whom 25 pathologic scars were treated (14 atrophic and 11 hypertrophic). All sessions were performed under sedation, and patients were discharged the same day, without the need for hospitalization. Regarding scar quality, an improvement was observed in the median Vancouver scale score at 6 weeks after the second session (7 points) compared to the initial median score (12 points), this difference being statistically significant (p = 0.031). No serious adverse effects were observed during the procedure or during subsequent follow-up, with a median follow-up of 14 weeks., Conclusions: Carboxytherapy is an effective and safe minimally invasive therapy for pathologic scars, achieving a significant improvement in scar quality, with almost no contraindications., Level of Evidence: Level IV., Type of Study: Prospective Single-Center Case Series., Competing Interests: Conflicts of interest The authors declare no conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The surgical treatment of otosclerosis consists of the replacement of the stapes using a piston., Aims/objectives: The objective of this study is to assess the audiometric results and quality of life (QOL) of patients who underwent surgery for otosclerosis by stapedectomy with fascia interposition (STIP) or by stapedotomy using CO 2 laser (SLaser) without fascia interposition., Material and Methods: Ninety-one patients operated on for otosclerosis by STIP (40 patients) and by SLaser (51 patients) were included. Audiometric results were graphically displayed using the Amsterdam Hearing Evaluation Plot and were compared to the Common Otology Database (COD) comprising 660 patients. The patients' QOL was assessed with an otological validated survey. The significance level was p  < .05., Results: There was no significant difference in hearing improvement between SLaser and STIP-operated patients. There was no significant difference between our results and that of COD. QOL was significantly improved (+3.5/10) postoperatively for both STIP and SLaser in both social and professional fields., Conclusions and Significance: By comparing QOL and hearing gain of STIP and SLaser, our results suggest that both surgical techniques are a safe and successful treatment for otosclerotic stapes fixation. Further studies aiming at comparing larger series may confirm and refine these results.

Importance: Mavacamten, a cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the EXPLORER-HCM study. However, the full extent of mavacamten's effects on exercise performance remains unclear., Objective: To investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET)., Design, Setting, and Participants: Exploratory analyses of the data from the EXPLORER-HCM study, a randomized, double-blind, placebo-controlled, phase 3 trial that was conducted in 68 cardiovascular centers in 13 countries. In total, 251 patients with symptomatic obstructive HCM were enrolled., Interventions: Patients were randomly assigned in a 1:1 ratio to mavacamten or placebo., Main Outcomes and Measures: The following prespecified exploratory cardiovascular and performance parameters were assessed with a standardized treadmill or bicycle ergometer test protocol at baseline and week 30: carbon dioxide output (VCO2), minute ventilation (VE), peak VE/VCO2 ratio, ventilatory efficiency (VE/VCO2 slope), peak respiratory exchange ratio (RER), peak circulatory power, ventilatory power, ventilatory threshold, peak metabolic equivalents (METs), peak exercise time, partial pressure of end-tidal carbon dioxide (PETCO2), and VO2/workload slope., Results: Two hundred fifty-one patients were enrolled. The mean (SD) age was 58.5 (11.9) years and 59% of patients were male. There were significant improvements with mavacamten vs placebo in the following peak-exercise CPET parameters: peak VE/VCO2 ratio (least squares [LS] mean difference, -2.2; 95% CI, -3.05 to -1.26; P < .001), peak METs (LS mean difference, 0.4; 95% CI, 0.17-0.60; P < .001), peak circulatory power (LS mean difference, 372.9 mL/kg/min × mm Hg; 95% CI, 153.12-592.61; P = .001), and peak PETCO2 (LS mean difference, 2.0 mm Hg; 95% CI, 1.12-2.79; P < .001). Mavacamten also improved peak exercise time compared with placebo (LS mean difference, 0.7 minutes; 95% CI, 0.13-1.24; P = .02). There was a significant improvement in nonpeak-exercise CPET parameters, such as VE/VCO2 slope (LS mean difference, -2.6; 95% CI, -3.58 to -1.52; P < .001) and ventilatory power (LS mean difference, 0.6 mm Hg; 95% CI, 0.29-0.90; P < .001) favoring mavacamten vs placebo., Conclusions and Relevance: Mavacamten improved a range of CPET parameters beyond pVO2, indicating consistent and broad benefits on maximal exercise capacity. Although improvements in peak-exercise CPET parameters are clinically meaningful, the favorable effects of mavacamten on submaximal exertional tolerance provide further insights into the beneficial impact of mavacamten in patients with obstructive HCM., Trial Registration: ClinicalTrials.gov Identifier: NCT03470545.

The objective of this study was to evaluate the efficacy and safety of super pulse CO 2 laser-assisted punctoplasty with canalicular curettage in primary canaliculitis. In this retrospective serial case study, the clinical data of 26 patients who underwent super pulse CO 2 laser-assisted punctoplasty for the treatment of canaliculitis were collected from January 2020 to May 2022. The clinical presentation, intraoperative and microbiologic findings, surgical pain severity, postoperative outcome, and complications were studied. Of the 26 patients, most were females (female:male 20:6), with a mean age of 60.1 ± 16.1 years (range, 19-93). Mucopurulent discharge (96.2%), eyelid redness and swelling (53.8%), and epiphora (38.5%) were the most common presentations. During the surgery, concretions were present in 73.1% (19/26) of the patients. The surgical pain severity scores ranged from 1 to 5, according to the visual analog scale, with a mean score of 3.2 ± 0.8. This procedure resulted in complete resolution in 22 (84.6%) patients and significant improvement in 2 (7.7%) patients, and 2 (7.7%) patients required additional lacrimal surgery with a mean follow-up time of 10.9 ± 3.7 months. The surgical procedure of super pulse CO 2 laser-assisted punctoplasty followed by curettage appears to be a safe, effective, minimally invasive, and well-tolerated treatment for primary canaliculitis., (© 2023. The Author(s).)

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis can be performed in two ways: first, the standard open abdominal technique (Open HIPEC); or second, the closed technique. In recent years, a new technique has been introduced to perform closed HIPEC; the Peritoneal Recirculation System (PRS-1.0 Combat) with CO 2 recirculation technology (PRS Closed HIPEC). The objective of this study is to present our experience with the PRS Closed HIPEC by comparing the intraoperative, postoperative and oncological results with the standard Open HIPEC technique (the Coliseum technique)., Methods: Data on patients undergoing CRS and HIPEC at the Sanchinarro University Hospital, Madrid from October 2012 to June 2021 were collected in a prospective database. The inclusion criteria were patients with primary or recurrent peritoneal metastases in gastrointestinal malignancies or ovarian cancer. The presence of an unresectable peritoneal carcinomatosis, the coexistence of another oncological disease, unresectable and distant metastases were the exclusion criteria., Results: From October 2014 to June 2021, 84 patients underwent CRS and HIPEC at the Sanchinarro University Hospital, Madrid with curative intent. Since the introduction of the PRS Closed HIPEC technique in 2016, 65 patients have been treated. Before the introduction of PRS Closed HIPEC, 19 cases were performed using the Coliseum technique (the Open HIPEC group). The intraoperative results were similar in the two groups. Complete cytoreduction was achieved in all cases in the Open HIPEC group and in 98% in the PRS Closed HIPEC group. The rate of major complications was similar between the groups. Median Overall Survival (OS) resulted better in the Closed HIPEC group (67 months) with respecto to the Open group (43 months) (p < 0,001). Median Disease-Free Survival (DFS) was 15 months in the Open HIPEC group and 40 months in the PRS Closed HIPEC group (p < 0.001)., Conclusion: The Peritoneal Recirculation System with CO 2 recirculation technology (PRS Closed HIPEC) is a reproducible and safe technique and may represent a valid alternative for the administration of HIPEC., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Acne vulgaris is caused by dyslipidemia, dyskeratosis and/or abnormal bacterial growth. The obstruction of skin pores due to hyperkeratosis of the infundibulum contributes to the formation of comedones. Thus, normalizing keratinization of epidermal cells in skin pores might be useful to improve acne. Recently, it has been found that the transcutaneous application of carbon dioxide (CO 2 ) regulates imbalances of the desquamatory process. In this study, we evaluated the efficacy of a skin lotion containing CO 2 on mild acne., Methods: Twenty-four healthy Japanese males (20-29 years old) with mild acne attended this evaluation. The subjects were divided into 2 groups, one group used a skin lotion containing CO 2 and the other group used a skin lotion without CO 2 . Following facial washing, each subject topically applied the skin lotion with or without CO 2 twice a day for 4 weeks. Prior to the start of the evaluation (week 0) and following 2 and 4 weeks of treatment, acne symptoms were assessed by a dermatologist and by instrumental measurements., Results: Topical application of the skin lotion with CO 2 for 4 weeks significantly improved acne symptoms, which was recognized by the subjects. However, treatment with the skin lotion without CO 2 did not improve acne symptoms. This improvement of acne symptoms by CO 2 was not accompanied by changes in sebum levels, skin surface pH, skin capacitance, or porphyrin levels., Conclusion: The transcutaneous application of a lotion with CO 2 improves acne symptoms by normalizing keratinization without affecting skin surface conditions., (© 2022 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objective: To analyze the application efficacy of the carboxytherapy method with the aim of chronic pain syndrome reduction., Material and Methods: The available literature sources, published in the period from 2017 to 2022 yrs and indexed in international abstract databases Scopus, Web of Science and PubMed, have been analyzed. The search was done by following keywords: carboxytherapy, medical rehabilitation, chronic pain. The patient with chronic pain syndrome, who was treated by carboxytherapy during rehabilitation, was also observed, with a subsequent evaluation of the carboxytherapy application in comprehensive treatment., Results: Analysis of available literature has shown that the different methodical variants of carboxytherapy are used to obtain analgesic, antispasmodic, anti-inflammatory and regenerative effects in patients with chronic pain. In the presented clinical case the use of carboxytherapy in the patient with chronic pain syndrome demonstrated the efficacy of technique, expressed in the positive dynamics in the evaluation of pain syndrome reduction on the visual analogue scale and the disability indicators in the Rollan Morris and Oswestry questionnaires., Conclusion: Carboxytherapy reduces the intensity of chronic pain syndrome and can be applied as an additional method in medical rehabilitation. Further studies in this direction are needed.

Introduction: Selective internal radiation therapy (SIRT) is a targeted method of treatment for unresectable liver tumors in which radiation therapy is directly delivered to the tumor(s) via the hepatic vasculature. Successful outcomes with SIRT are dependent on the specific vasculature of the liver and tumor, and the patient therefore needs to attend a "work-up" to map the hepatic vasculature prior to the SIRT procedure. Recent advances in SIRT delivery have enabled same-day or same-stay work-up and procedure, requiring only one hospital visit rather than two. We aimed to evaluate the economic, travel time, and transport-related environmental impact of a new brachytherapy device delivery program, the order-map-treat (OMT) program, in patients with unresectable hepatocellular carcinoma (HCC) in England., Methods: A healthcare resource group (HRG)-based analysis of costs from a national payer (Department of Health and Social Care, DHSC) perspective was conducted assuming that, with OMT, patients would have to attend hospital only once for both the SIRT work-up and procedure versus twice without OMT. Patient travel time and CO 2 emissions were then estimated by identifying the SIRT center closest to the centroid of each clinical commissioning group (CCG) and calculating straight-line distances with a "detour index" to capture the effect of indirect routes via road or rail., Results: It was estimated that 856 patients per annum would be eligible for SIRT treatment for unresectable HCC in England. OMT would be anticipated to save GBP 2842 per patient versus performing SIRT without OMT. Furthermore, across all patients with HCC eligible for SIRT in England, OMT would avoid 74,500 km of travel, 2299 h of travel time, and 13.9 metric tons of patient transport-related CO 2 emissions annually., Conclusion: OMT reduces the number of hospital visits required for SIRT by 50%, resulting in financial savings from the DHSC perspective, time savings from the patient perspective, and reduced CO 2 emissions arising from patient transport., (© 2022. The Author(s).)

The aim of this study is to investigate and analyze the effect of different application sequences of CO 2 fractional laser and triamcinolone acetonide injection on the application effect of hypertrophic scar in one operation. Patients with hypertrophic scars who received CO 2 lattice laser combined with triamcinolone acetonide injection from January 2021 to December 2022 were retrospectively analyzed. According to the different initial operations, they were divided into CO 2 FL-TA group and TA-CO 2 FL group. The Vancouver Scar Scale score and scar thickness of the two groups before and after treatment were analyzed. The complications occurred in the two groups during the treatment period. The clinical efficacy of the two groups before and after the treatment was calculated. Before treatment, there was no difference in scar thickness and VSS score between the two groups (P > 0.05). After treatment, the above indexes in CO 2 FL-TA group were significantly better than those in TA-CO 2 FL group (P < 0.05); the incidence of adverse reactions in CO 2 FL-TA group was 9.38%, which was significantly lower than that in TA-CO 2 FL group (18.75%) (P < 0.05); the total effective rate of CO 2 FL-TA group was 90.63%, which was significantly higher than that in TA-CO 2 FL group (65.63%) (P < 0.05). In the process of combined CO 2 fractional laser and triamcinolone acetonide injection in the treatment of hypertrophic scars, CO 2 fractional laser treatment first, and then triamcinolone acetonide injection can reduce the number of treatments, reduce the incidence of adverse reactions, and achieve more satisfactory treatment effect., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Alopecia areata (AA) is a disease that affects the psychological well-being of the affected individuals. Laser-assisted drug delivery and microneedling (MN) are promising methods for the treatment of different dermatological diseases. The aim of the study was to compare the efficacy of topical application of triamcinolone acetonide after fractional carbon dioxide laser versus MN in the treatment of resistant AA from a clinical and dermoscopic perspective. Thirty patients were randomly divided into two groups of 15 patients each: the Laser group received fractional CO 2 laser treatment followed by topical application of triamcinolone acetonide, and the MN group received dermapen treatment followed by topical application of triamcinolone acetonide. In our study, we found no statistically significant difference between the studied groups before and after treatment, except for black dot, which is higher in the MN group than in the laser group (46.7% vs. 13.3%). There is a statistically significant difference between the studied groups in terms of treatment response at the first follow-up, with 13.3% of the laser group seeing terminal hair regrowth compared to 0 in the MN group after 12 weeks. Regarding the degree of improvement, there was no statistically significant difference between the laser group and the MN group. The use of fractional CO 2 laser and MN for transepidermal drug delivery (TED) allowed for more uniform drug distribution. There was no significant difference between the two treatment methods in terms of their high effectiveness in the treatment of resistant AA., (© 2022 Wiley Periodicals LLC.)

To compare the therapeutic effect of fractional carbon dioxide (CO 2 ) laser + topical triamcinolone (TA) with intralesional TA on keloids. Twenty-two participants were randomised into two groups: group A, treated with fractional CO 2 laser + topical TA, and group B, treated with intralesional TA. The interventions were performed at every 4-week interval until the keloids were resolved or at the completion of 1 year. At each session, the scar volume, Vancouver Scar Scale (VSS) were assessed. Recurrence was observed for 1 year. The mean scar volumes and VSS scores were not significantly different between the two groups. After 1 year, the scar volume change in group B was greater than group A (86.5% vs 59.1%, P-value = .016). The mean VSS scores were significantly decreased in group A (8.0 ± 1.5 to 4.8 ± 1.6, P-value <.001) and group B (8.4 ± 0.8 to 4.8 ± 1.6, P-value <.001). The keloids were completely resolved in 63.6% and 72.7% of the patients, and recurrence was observed in 9.1% and 18.2% of the patients in groups A and B, respectively. The combination of fractional CO 2 laser with topical TA was an alternative option for the treatment of keloids., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Background: Fractional carbon dioxide (CO2) laser has been considered to be an add-on to conventional treatments of vitiligo., Objective: This study aimed to evaluate the optimal energy and density of the fractional CO2 laser system in stable non-segmental vitiligo (NSV) patients., Method: 48 patients were treated with fractional CO2 laser and sequential phototherapies of narrowband ultraviolet B (NB-UVB), after the CO2 laser treatment, a compound betamethasone solution was topically applied. For the fractional CO2 laser, coverages of 8% and 12.6% were set as low density (Ld) and high density (Hd), and energies of 60 mJ and 80 mJ were set as low energy (Le) and high energy (He), respectively. The patients were randomly assigned to Group A (HeHd), Group B (HeLd) or Group C (LeLd)., Results: Either after 3 or 6 months of enrollment, the efficacy of Group C was better than Group B (p < 0.05). No difference was seen between Group A and Group B or Group A and Group C (p > 0.05). More patients complained higher pain score in Group A as compared with Group C (p < 0.05)., Conclusion: The optimal parameters of the fractional CO2 laser were energy at 60 mJ and density at 8%., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The primary physiological process of respiration produces carbon dioxide (CO 2 ) that reacts with water molecules which subsequently liberates bicarbonate (HCO- 3 ) and protons. Carbonic anhydrases (CAs) are the primary catalyst involved in this conversion. More than 16 isoforms of human CAs show organ or subcellular specific activity. Dysregulation of each CA is associated with multiple pathologies. Out of these members, the overexpression of membrane-bound carbonic anhydrase IX (CAIX) is associated explicitly with hypoxic tumors or various solid cancers. CAIX helps tumors deal with higher CO 2 by sequestering it with bicarbonate ions and helping cancer cells to grow in a comparatively hypoxic or acidic environment, thus acting as a pH adaptation switch. CAIX-mediated adaptations in cancer cells include angiogenesis, metabolic alterations, tumor heterogeneity, drug resistance, and regulation of cancer-specific chemokines. This review comprehensively collects and describe the cancer-specific expression mechanism and role of CAIX in cancer growth, progression, heterogeneity, and its structural insight to develop future combinatorial targeted cancer therapies., Competing Interests: Declaration of Competing Interest Authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However, some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid-dependent individuals receiving methadone., Methods: Opiate-dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800 IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60, or 90 mg) based on the incidence of 'dose-limiting toxicity' (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular, and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 h later. Measures including oxygen saturation, transcutaneous CO 2 , respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone), and adverse events will be obtained using validated questionnaires and examinations periodically for 5 h after dosing., Discussion: Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone, to inform a subsequent proof-of-concept trial of the efficacy baclofen to facilitate opiate detoxification. To proceed, the minimum acceptable dose is 30 mg of baclofen in patients receiving ≤ 60 mg/day methadone based on the clinical experience of baclofen's use in alcoholism and guidelines for the management of opiate dependence., Trial Registration: Clinicaltrials.gov NCT05161351. Registered on 16 December 2021., (© 2022. The Author(s).)

Objective: Aerosol inhalation is commonly used in the treatment of chronic obstructive pulmonary emphysema (COPE). This study aimed to evaluate the effectiveness of aerosol inhalation combined with a vibration expectoration machine on COPE., Methods: From June 2019 to June 2020, 110 patients receiving COPE treatment in Linyi Central Hospital in China were included in this randomized controlled trial. All patients were randomly assigned into one of two groups using the random number table. A total of 55 patients were given aerosol inhalation combined with the use of a vibration expectoration machine in the study group, and 55 patients were given aerosol inhalation alone in the control group. The general data, clinical efficacy arterial blood gas index, pulmonary function index and serum levels of insulin-like growth factor 1 (IGF-1), alpha 1 antitrypsin (α1-AT) and platelet-derived growth factor-B (PDGF-B) were compared., Results: There was no difference in baseline characteristics between the 2 groups (P > .05). After treatment, the clinical efficacy in the study group was significantly higher than in the control group (96.36% vs 81.82%, respectively; P = .023), daily sputum production in the study group was significantly higher compared with the control group (80.92 ± 10.29 vs 58.63 ± 9.02 ml, respectively; P < .001) and hospitalization time was significantly reduced in the study group (11.87 ± 1.76 vs 17.62 ± 1.92 days, respectively; P < .001). In addition, the respiratory rate was significantly lower in the study group (17.43 ± 1.61 vs 22.08 ± 3.25, respectively; P < .001). Partial pressure of oxygen (P[O2]) was significantly higher (76.29 ± 7.34 vs 66.81 ± 7.93 mmHg, respectively; P < .001) and partial pressure of carbon dioxide (P[CO2]) was significantly lower (34.82 ± 6.02 vs 39.83 ± 6.01 mmHg respectively; P < .001) in the study group compared with the control group. In addition, forced expiratory volume in the first second (FEV1) (1.79 ± 0.36 vs 1.66 ± 0.28 L, respectively), forced vital capacity (FVC) (2.58 ± 0.28 vs 2.42 ± 0.11 L, respectively), forced expiratory volume in the first second as a percentage of the predicted value (FEV1%pred) (65.32 ± 4.03 vs 59.83 ± 4.76 L, respectively) and maximal mid-expiratory flow (MMEF) (1.51 ± 0.27% vs 1.36 ± 0.12%, respectively) were all significantly increased after treatment in the study group compared with the control group (all P < .001). The IGF-1 (104.92 ± 11.27 vs 137.83 ± 11.02 ng/mL, respectively) and PDGF-B (124.39 ± 14.29 vs 249.93 ± 33.49 ng/L, respectively) were significantly reduced in the study group after treatment (all P < .001). The α1-AT (2.82 ± 0.38 vs 2.17 ± 0.22 g/L, respectively) were significantly increased after treatment in the study group compared with the control group., Conclusion: Aerosol inhalation combined with the use of a vibration expectoration machine is worthy of clinical application, and can effectively improve outcomes in patients with COPE.

To explore the curative effect of antibiotic combined with mucosolvan perfusion under fiber bronchoscope in treatment of pneumonia after severe cerebral hemorrhage. The clinical data of 120 patients with pneumonia after severe cerebral hemorrhage admitted to our hospital from January 2017 to December 2019 were collected. All patients were divided into the lavage group and perfusion group by random number method, with 60 patients in each group. Patients in the lavage group received antibiotics combined with mucosolvan lavage therapy under fiber bronchoscope, while patients in the perfusion group received antibiotics combined with mucosolvan perfusion therapy under fiber bronchoscope. Clinical pulmonary infection score (CPIS), arterial blood gas index, clinical symptom improvement, and hospitalization costs were compared between the two groups before and after treatment. CPIS scores were improved after treatment in both groups (P < .05), and CPIS scores of patients in the perfusion group were lower than those in the lavage group at 3, 5, and 7 days after treatment (P < .05). The blood oxygen saturation and partial arterial oxygen pressure of the perfusion group were all higher than those of the lavage group (P < .05), while the partial carbon dioxide pressure was lower than that of the lavage group (P < .05). In the perfusion group, the duration of cough, adequacy of fever, disappearance of rhonchus in the lungs, and the length of hospital stay were less than those in the lavage group (P < .05). The hospitalization costs of perfusion group were lower than that of lavage group (P < .05). The combination of antibiotics and mucosolvan infusion therapy under fiber bronchoscope can effectively improve the clinical efficacy, reduce the hospitalization cost, and improve the prognosis of patients with pneumonia after severe cerebral hemorrhage., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Striae Distensae (SD) are quite common complaint in dermatology practice. They are linear lesions of variable length and width according to the site and the causative condition. Several treatment modalities have been tried. To achieve satisfactory results, a combination therapy is often needed. To evaluate the efficacy and safety of fractional CO 2 laser versus carboxytherapy in the treatment of Striae Distensae clinically and radiologically. Thirty Egyptian patients with striae distensae, received a split body therapy: the left side was treated by fractional CO 2 laser and the right side was treated by carboxytherapy in the same session. Six sessions were done with 4 weeks apart. Clinical evaluation by measurement of the width of widest striae on both sides, global aesthetic improvement scale (GAIS), and Likert satisfaction scale. Radiological evaluation by measurement of cutaneous thickness of widest striae on both sides by ultrasonography. There was a highly statistically significant decrease in the median width of the widest striae distensae on both sides after the last session (P < 0.01). Regarding GAIS, satisfaction scale and ultrasound, there was highly statistically significant improvement on laser side than carboxytherapy side (P < 0.01) after last session. Both fractional CO 2 laser and carboxytherapy may be considered as safe and effective lines of treatment for striae distensae, but fractional CO 2 laser showed excellent improvement clinically, radiologically when compared with carboxytherapy which made it a promising module in treatment of striae distensae., (© 2022 Wiley Periodicals LLC.)

Background: Updates of treatment methods of stable vitiligo are needed to give better outcomes with a shorter duration of treatment., Objective: To test the effect of transdermal 5-fluorouracil (5-FU) delivery using fractional CO 2 (FrCO 2 ) laser versus intralesional 5-FU injection, with narrow-band type ultraviolet B (UVB) (NB-UVB) therapy after both, in the treatment of stable vitiligo., Patients and Methods: The present study comprised 40 patients with nearly symmetrical stable vitiligo lesions. The left side was treated with FrCO 2  laser followed by topical 5-FU (FrCO 2  + 5-FU), while the right side was treated with 5-FU intradermal injection. Both procedures were done at 2-week intervals for 3 sessions followed by 24 sessions of narrow-band UVB for both sides., Results: Repigmentation was demonstrated on the left side of 90% of patients and the right side of 85% of patients. As much as >50% improvement was demonstrated on the left side of 50% of patients, and the right side of 55% of patients. Intralesional 5-FU showed a statistically significant difference in repigmentation compared to FrCO 2  + 5-FU., Conclusion: Both 5-FU injection and FrCO 2  + 5-FU were effective therapeutic modalities for vitiligo. Patients were more compliant with FrCO 2  + 5-FU., (© 2021 Wiley Periodicals LLC.)

Management of alopecia areata (AA) is often challenging especially when patients have AA lesion refractory to conventional treatments such as corticosteroids, contact immunotherapy, and systemic therapy. Reports indicate adipocyte-derived stem cell conditioned media (ASC-CM) can activate hair growth and micro-injury using fractional laser or microneedling can also induce wound healing and hair regeneration, which suggests ASC-CM combined with fractional laser or microneedling might provide alternative therapeutic option for a refractory patch of AA. This study aimed to evaluate the clinical efficacy and safety of ASC-CM combined with 10,600 nm carbon dioxide fractional laser or microneedling for the treatment of refractory patch of AA. This retrospective study was based on evaluations of 14 patients with a refractory patch of AA treated with ASC-CM, combined with a 10,600 nm carbon dioxide fractional laser, or microneedling from March 2017 to August 2020. The efficacy of treatment was assessed by extents of hair regrowth percentages of involved areas. Of the 14 enrolled patients, 9 (64.3%) showed > 50% hair regrowth and 6 patients (42.9%) showed complete recovery. In the responder group (n = 9), mean period to achieve > 50% hair regrowth was 11.3 weeks (range 8-16 weeks). In the non-responder group (n = 5), 4 patients (28.6%) showed < 25% of hair regrowth and 1 patient show slight hair regrowth (7.1%) after 3 months of treatment. This study showed ASC-CM combined with 10,600 nm carbon dioxide fractional laser or microneedling may offer effective and safe treatment options for a refractory patch of AA., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sneathia sanguinegens is a fastidious, Gram-negative, rod-shape organism rarely isolated from human specimens. In the present report, we describe a case of periprosthetic knee joint infection due to the organism, which occurred in a female patient receiving immunosuppressants for underlying lupus nephritis. The causative organism was isolated from the synovial fluid in the affected knee joint through inoculating the material on chocolate agar and incubation for 15 days under 5% CO 2 . Moreover, the organism was capable to be subcultured on chocolate agar with incubation for a few days under 5% CO 2 , demonstrating that this uncommon organism, although generally considered as a strict anaerobe, is culturable in aerobic condition if appropriate media and a sufficient incubation time are given. The patient was treated with intravenous cefepime, an antibiotic highly active to the isolated organism in an in vitro study, in addition to intraarticular debridement and exchanging a polyethylene insert in the affected joint. The antimicrobial therapy with cefepime was given for 19 days and, thereafter, changed with oral levofloxacin. Although the patient showed full recovery after administration of levofloxacin for 100 days, an in vitro study conducted later revealed that levofloxacin was inactive to the isolated organism., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

New treatment modalities are rising for better clinical improvement in alopecia areata. This work aims to evaluate the efficacy of fractional CO 2 laser and microneedling as a transepidermal drug delivery in cases with alopecia areata. The study included 30 patients with alopecia areata. All lesions in each patient have received randomly two different treatment modalities, fractional CO 2 laser or microneedling followed by triamcinolone acetonide (TA) application according to group assignment. Sessions were done every month for a maximum of six sessions or complete resolution. Response to treatment was assessed on SALT score and dermoscopic imaging. Both treatment modalities showed a significant clinical improvement of alopecia areata, with a statistically significant reduction of SALT score for fractional CO 2 laser group and microneedling group (p value <0.001). Moreover, there is a significant difference in the SALT score between both modalities (p = 0.013), whereas the reduction of the SALT score was more evident in microneedling group. On comparing the dermoscopy findings in fractional CO 2 laser and microneedling treated areas before and after treatment, a significant reduction was found regarding all dermoscopic findings of alopecia areata. Fractional CO 2 laser and microneedling as a transepidermal drug delivery could be a novel and effective treatment modality in alopecia areata. Dermoscopy is very useful to identify disease activity and early signs of clinical improvement during treatment., (© 2022 Wiley Periodicals LLC.)

Current therapeutic agents for onychomycosis have limited efficacy or cause side effects. Recently, successful treatment using fractional CO 2 lasers has been reported; however, the results are inconsistent. We analyzed the real-world effectiveness of a Fractional CO 2 laser for the treatment of Onychomycosis A single-center retrospective chart review was conducted during January 2015-December 2018. Patients, diagnosed with onychomycosis through fungal culture and/or potassium hydroxide staining, underwent three or more fractional CO 2 laser treatments and used topical antifungal agents. Treatment effects were assessed by using clinical images at 6, 12 months, and the last visit. Ninety-six patients were included; they underwent an average of 7.7 laser treatment sessions. Finally, 15 patients (15.6%) showed complete response (100% clearing of all nails), 24 patients (25%) showed partial response, and 57 patients (59.4%) showed no response (no 100% clearing of nails among all treated toenails per patient including mild improvement or temporary cosmetic improvement). Multivariable logistic regression analysis revealed longer disease duration (p = 0.006, OR = 1.16 [95% CI: 1.05-1.31]), patients with diabetes (p = 0.021, OR = 9.82 [95% CI: 1.75-94.01]) and fewer number of laser treatment sessions (p = 0.001, OR = 0.76 [95% CI: 0.64-0.89]) were significantly associated with non-response group. In conclusion, fractional CO 2 laser with topical antifungal could be a safe alternative treatment in patients with onychomycosis, who are difficult to take oral antifungals., (© 2022 Wiley Periodicals LLC.)