Acromegaly and pregnancy: a systematic review and meta-analysis.

PURPOSE: To evaluate the association between acromegaly and pregnancy in terms of disease activity, maternal and fetal outcomes. METHODS: This systematic review was conducted according to the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. We focused on observational studies that included pregnant women with acromegaly. The outcomes were acromegaly activity, preterm birth, gestational diabetes, hypertension, eclampsia/preeclampsia, miscarriage, perinatal mortality, low birthweight, small for gestational age, and congenital malformations. Embase, Medline, LILACS, and CENTRAL were our source databases. To perform proportional meta-analyses, we used Stata Statistical Software 17. RESULTS: Nineteen studies were included encompassing a total of 273 pregnancies in 211 women with acromegaly. The overall frequency of control of acromegaly during pregnancy was 62%, and of tumor growth was 9%. No fetal or maternal deaths were reported. The overall frequency of worsening of previous diabetes or development of gestational diabetes was 9%, and of previous hypertension or preeclampsia/eclampsia was 6%. The overall frequency of premature labor was 9% [from 17 studies of 263 pregnancies; 95% confidence interval (CI), 5-13%]; of spontaneous miscarriage was 4% (from 19 studies of 273 pregnancies; 95% CI, 2-11%); of small for gestational age was 5% (from 15 studies of 216 newborns; 95% CI, 3-9%); and of congenital malformations was 1% (from 18 studies of 240 newborns; 95% CI, 0-7%). CONCLUSION: Pregnancy in women with acromegaly is frequently associated with disease control and is safe in relation to fetal and maternal outcomes, as in women without acromegaly.

Systematic review and meta-analysis of the safety of chloroquine and hydroxychloroquine from randomized controlled trials on malarial and non-malarial conditions.

BACKGROUND: Despite the expectations regarding the effectiveness of chloroquine (CQ) and hydroxychloroquine (HCQ) for coronavirus disease (COVID-19) management, concerns about their adverse events have remained. OBJECTIVES: The objective of this systematic review was to evaluate the safety of CQ and HCQ from malarial and non-malarial randomized clinical trials (RCTs). METHODS: The primary outcomes were the frequencies of serious adverse events (SAEs), retinopathy, and cardiac complications. Search strategies were applied to MEDLINE, EMBASE, LILACS, CENTRAL, Scopus, and Trip databases. We used a random-effects model to pool results across studies and Peto's one-step odds ratio (OR) for event rates below 1%. Both-armed zero-event studies were excluded from the meta-analyses. We used the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the certainty of evidence. RESULTS: One hundred and six RCTs were included. We found no significant difference between CQ/HCQ and control (placebo or non-CQ/HCQ) in the frequency of SAEs (OR: 0.98, 95% confidence interval [CI]: 0.76-1.26, 33 trials, 15,942 participants, moderate certainty of evidence). However, there was a moderate certainty of evidence that CQ/HCQ increases the incidence of cardiac complications (RR: 1.62, 95% CI: 1.10-2.38, 16 trials, 9908 participants). No clear relationship was observed between CQ/HCQ and retinopathy (OR: 1.63, 95% CI: - 0.4-6.57, 5 trials, 344 participants, very low certainty of evidence). CONCLUSIONS: CQ and HCQ probably do not increase SAEs, with low frequency of these adverse events on malarial and non-malarial conditions. However, they may increase cardiac complications especially in patients with COVID-19. No clear effect of their use on the incidence of retinopathy was observed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020177818.

Evaluation of ex vivo melanogenic response to UVB, UVA, and visible light in facial melasma and unaffected adjacent skin,

Abstract Background: The independent role of solar radiation in the differential melanogenesis between melasma and adjacent skin is unknown. Objectives: To assess the melanogenic responses of skin with facial melasma and of the adjacent skin to UVB, UVA, and visible light, in an ex vivo model. Methods: This was a quasi-experimental study involving 22 patients with melasma. Facial melasma and adjacent skin samples were collected and stored in DMEM medium, at room temperature. One fragment was placed under the protection from light, while another was exposed to UVB, UVA, and visible light (blue-violet component): 166 mJ/cm2, 1.524 J/cm2, and 40 J/cm2, respectively. Subsequently, all samples were kept for 72 hours in a dark environment and stained by Fontana-Masson to assess basal layer pigmentation, dendrites, and melanin granulation. Results: Effective melanogenesis was observed in the basal layer in melasma and in the normal adjacent skin after all irradiations (p< 0.01), with the following median increment: UVB (4.7% vs. 8.5%), UVA (9.5% vs. 9.9%), and visible light (6.8% vs. 11.7%), with no significant difference between anatomical sites. An increase in melanin granulation (coarser melanosomes) was observed only after irradiation with UVA and only in the skin with melasma (p= 0.05). An increase in the melanocyte dendrite count induced by UVB radiation was observed in both anatomical sites (p≤ 0.05). Study limitations: Use of an ex vivo model, with independent irradiation regimes for UVB, UVA, and visible light. Conclusions: Melanogenesis induced by UVB, UVA, and visible light was observed both in melasma and in the adjacent skin. The morphological patterns suggest that different irradiations promote individualized responses on the skin with melasma.

Evaluation of ex vivo melanogenic response to UVB, UVA, and visible light in facial melasma and unaffected adjacent skin.

BACKGROUND: The independent role of solar radiation in the differential melanogenesis between melasma and adjacent skin is unknown. OBJECTIVES: To assess the melanogenic responses of skin with facial melasma and of the adjacent skin to UVB, UVA, and visible light, in an ex vivo model. METHODS: This was a quasi-experimental study involving 22 patients with melasma. Facial melasma and adjacent skin samples were collected and stored in DMEM medium, at room temperature. One fragment was placed under the protection from light, while another was exposed to UVB, UVA, and visible light (blue-violet component): 166 mJ/cm2, 1.524 J/cm2, and 40 J/cm2, respectively. Subsequently, all samples were kept for 72 hours in a dark environment and stained by Fontana-Masson to assess basal layer pigmentation, dendrites, and melanin granulation. RESULTS: Effective melanogenesis was observed in the basal layer in melasma and in the normal adjacent skin after all irradiations (p < 0.01), with the following median increment: UVB (4.7% vs. 8.5%), UVA (9.5% vs. 9.9%), and visible light (6.8% vs. 11.7%), with no significant difference between anatomical sites. An increase in melanin granulation (coarser melanosomes) was observed only after irradiation with UVA and only in the skin with melasma (p = 0.05). An increase in the melanocyte dendrite count induced by UVB radiation was observed in both anatomical sites (p ≤ 0.05). STUDY LIMITATIONS: Use of an ex vivo model, with independent irradiation regimes for UVB, UVA, and visible light. CONCLUSIONS: Melanogenesis induced by UVB, UVA, and visible light was observed both in melasma and in the adjacent skin. The morphological patterns suggest that different irradiations promote individualized responses on the skin with melasma.

Standardization of organoid culture for evaluation of melanogenesis induced by UVB, UVA and visible light

Abstract Background: Organoid cultures are primary cultures that maintain architectural characteristics and the relationships between cells, as well as the extracellular matrix. They are alternatives for pathophysiological or therapeutic investigation rather than animal and in vitro tests. Objective: Development of a cutaneous organoid culture model, aiming at the study of radiation-induced melanogenesis. Method: A validation study, which involved biopsies of the skin of the back of the adult ear. One sample was irradiated with different doses of UVB, UVA, or visible light (VL); the other was maintained in the dark for 72 h. The viability of the tissues was evaluated from the morphological and architectural parameters of the histology, and the expression of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, by real-time polymerase chain reaction (PCR). The radiation-induced melanin pigmentation was standardized according to the doses of each radiation and evaluated by digital image analysis (Fontana-Masson). Results: The primary skin culture was standardized at room temperature using DMEM medium. The doses of UVB, UVA, and VL (blue light) that induced differential melanogenesis were: 166 mJ/cm2, 1.524 J/cm2, and 40 J/cm2. The expression of the GAPHD constitutional gene did not differ between the sample of skin processed immediately after tissue collection and the sample cultured for 72 h in the standardized protocol. Study limitations: This was a preliminary study that evaluated only the viability and integrity of the melanogenic system, and the effect of the radiation alone. Conclusions: The standardized model maintained viable melanocytic function for 72 h at room temperature, allowing the investigation of melanogenesis induced by different forms of radiation.

Standardization of organoid culture for evaluation of melanogenesis induced by UVB, UVA and visible light.

BACKGROUND: Organoid cultures are primary cultures that maintain architectural characteristics and the relationships between cells, as well as the extracellular matrix. They are alternatives for pathophysiological or therapeutic investigation rather than animal and in vitro tests. OBJECTIVE: Development of a cutaneous organoid culture model, aiming at the study of radiation-induced melanogenesis. METHOD: A validation study, which involved biopsies of the skin of the back of the adult ear. One sample was irradiated with different doses of UVB, UVA, or visible light (VL); the other was maintained in the dark for 72h. The viability of the tissues was evaluated from the morphological and architectural parameters of the histology, and the expression of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene, by real-time polymerase chain reaction (PCR). The radiation-induced melanin pigmentation was standardized according to the doses of each radiation and evaluated by digital image analysis (Fontana-Masson). RESULTS: The primary skin culture was standardized at room temperature using DMEM medium. The doses of UVB, UVA, and VL (blue light) that induced differential melanogenesis were: 166mJ/cm2, 1.524J/cm2, and 40J/cm2. The expression of the GAPHD constitutional gene did not differ between the sample of skin processed immediately after tissue collection and the sample cultured for 72h in the standardized protocol. STUDY LIMITATIONS: This was a preliminary study that evaluated only the viability and integrity of the melanogenic system, and the effect of the radiation alone. CONCLUSIONS: The standardized model maintained viable melanocytic function for 72h at room temperature, allowing the investigation of melanogenesis induced by different forms of radiation.