A systematic review of the safety and efficacy of currently used treatment modalities in the treatment of patients with PIK3CA-related overgrowth spectrum.

BACKGROUND: PIK3CA (activating mutations of the p110α subunit of phosphatidylinositol 3-kinases)-related overgrowth spectrums (PROS) include a variety of clinical presentations that are associated with hypertrophy of different parts of the body. We performed a systematic literature review to assess the current treatment options and their efficacy and safety for PROS. METHODS: A literature search was performed in Embase, MEDLINE (Ovid), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar to retrieve studies on the treatment of hypertrophy in PROS. Randomized controlled trials, cohort studies, and case series with ≥10 patients were included in the present review. The titles, abstracts, and full text were assessed by two reviewers independently. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: We included 16 studies of the treatment of hypertrophy in PROS patients, 13 (81.3%) from clinical retrospective studies and 3 (13.7%) from prospective cohort studies. The risk of bias grade was low for 2, medium for 12, and high for 2 studies. Of the 16 studies, 13 reported on surgical treatment and 3 reported pharmacologic treatment using phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway inhibitors in PROS patients. In 3 studies, PROS was defined by a mutation in the PIK3CA gene, and 13 studies relied on a clinical definition of PROS. Surgical therapy was beneficial for a specific subgroup of PROS (macrodactyly). However, little has been reported concerning surgery and the potential benefits for other PROS entities. The reported side effects after surgical therapy were mostly prolonged wound healing or scarring. PI3K/mTOR pathway inhibition was beneficial in patients with PROS by reducing hypertrophy and systemic symptoms. The adverse effects reported included infection, changes in blood count, liver enzymes, and metabolic measures. CONCLUSIONS: Surgery is a locally limited treatment option for specific types of PROS. A promising treatment option for PROS is pharmacologic PIK3CA inhibition. However, the level of evidence on the treatment of overgrowth in PROS patients is limited.

A novel multi-study intervention investigating the short and long term effects of a posture bra on whole body and breast kinematics.

BACKGROUND: Poor standing posture has been reported in women with larger breasts, increasing the risk of back pain. Whilst breast reduction surgery can improve posture, conservative measures such as special bras may offer short or long-term relief of symptoms without surgical intervention. RESEARCH QUESTION: This study aimed to utilise a multi-study intervention to investigate the short and long-term kinematic effects of wearing a posture bra. METHODS: Study one utilised biomechanics and physiotherapy expertise to modify the design of a prototype bra to improve posture and breast kinematics; resulting in a second-generation posture bra. To test this bra, 24 females were randomly assigned to control and intervention groups. The control group wore their everyday bra; the intervention group wore the generation 2 posture bra in place of their everyday bra for three months. Pre and post intervention, posture (spine curvature, scapula position, whole body alignment) and breast kinematics were assessed during sitting, standing and walking. Short-term effects of the posture bra were compared to an everyday bra and no bra (study two), whilst the long-term effects were compared using the no bra condition (study three). RESULTS: Biomechanical intervention improved posture and breast kinematics in a prototype posture bra resulting in a second-generation prototype. Pre-intervention, the generation 2 posture bra significantly improved scapula retraction by 6° during both sitting and standing, but also increased deviation of whole body alignment compared to everyday bra and no bra conditions. During walking the posture bra reduced breast motion by 17 % compared to the everyday bra. Following the three-month wearer intervention, scapula depression significantly improved in the intervention group. SIGNIFICANCE: A biomechanically informed posture bra was able to effectively support the breasts and improve scapula position without compromising spinal curvature, reducing the risk of musculoskeletal pain associated with poor posture.

Matrilin-3-Primed Adipose-Derived Mesenchymal Stromal Cell Spheroids Prevent Mesenchymal Stromal-Cell-Derived Chondrocyte Hypertrophy.

Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for articular cartilage repair and regeneration. However, the terminal hypertrophic differentiation of Ad-MSC-derived cartilage is a critical barrier during hyaline cartilage regeneration. In this study, we investigated the role of matrilin-3 in preventing Ad-MSC-derived chondrocyte hypertrophy in vitro and in an osteoarthritis (OA) destabilization of the medial meniscus (DMM) model. Methacrylated hyaluron (MAHA) (1%) was used to encapsulate and make scaffolds containing Ad-MSCs and matrilin-3. Subsequently, the encapsulated cells in the scaffolds were differentiated in chondrogenic medium (TGF-ß, 1-14 days) and thyroid hormone hypertrophic medium (T3, 15-28 days). The presence of matrilin-3 with Ad-MSCs in the MAHA scaffold significantly increased the chondrogenic marker and decreased the hypertrophy marker mRNA and protein expression. Furthermore, matrilin-3 significantly modified the expression of TGF-ß2, BMP-2, and BMP-4. Next, we prepared the OA model and transplanted Ad-MSCs primed with matrilin-3, either as a single-cell suspension or in spheroid form. Safranin-O staining and the OA score suggested that the regenerated cartilage morphology in the matrilin-3-primed Ad-MSC spheroids was similar to the positive control. Furthermore, matrilin-3-primed Ad-MSC spheroids prevented subchondral bone sclerosis in the mouse model. Here, we show that matrilin-3 plays a major role in modulating Ad-MSCs' therapeutic effect on cartilage regeneration and hypertrophy suppression.

The efficacy and safety of Chinese herbal compound or combined with western medicine for pediatric adenoidal hypertrophy: A protocol for systematic review and meta-analysis.

BACKGROUND: Traditional Chinese medicine (TCM) or combined with western medicine in the treatment of pediatric adenoidal hypertrophy has been widely used in clinical practice, but the overall efficacy and safety is still unclear. This paper aims to evaluate the efficacy and safety analysis of TCM or combined with western medicine for pediatric adenoidal hypertrophy. METHODS: PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) were searched for randomized controlled trials of TCM or combined with western medicine for pediatric adenoidal hypertrophy from the date of establishment to July 2020, and Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform (ICTRP), and Chinese Clinical Trials Registry (ChiCTR) were searched for unpublished grey literature. Two researchers independently applied RevMan 5.3 software for data extraction and risk assessment of bias. RESULTS: The effectiveness and safety of TCM or combined with western medicine for pediatric adenoidal hypertrophy is evaluated by means of the Adenoid (A) /(Nasopharyngeal (N) ratio, clinical efficacy, integral score of TCM syndromes, clinical single symptom score, disease specific quality of life for children with obstructive sleep apnea 18 items survey (OSA-18), Interleukin 4 (IL-4) and adverse reaction incidence. CONCLUSION: This study will provide theoretical support for the clinical application of TCM or combined with western medicine for pediatric adenoidal hypertrophy. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/J76AG.

[Ex-Utero Intrapartum Treatment for airway management in congenital giant neck masses]. / Técnica EXIT como manejo de la vía aérea en masas gigantes congénitas de cuello.

INTRODUCTION: Congenital head and neck masses are associated with perinatal asphyxia and brain injury, increasing the risk of death. The EXIT (Ex Utero Intrapartum Treatment) technique con sists of ensuring the newborn's airway while is still receiving placental support. This technique has not been standardized in developing countries. OBJECTIVE: To describe the clinical outcomes of two infants who underwent the EXIT technique. CLINICAL CASE: We present two cases, one with lymphatic malformation diagnosed at 20 weeks of gestational age (WGE) and the second one, a preterm newborn with thyromegaly and polyhydramnios, diagnosed at 35 WGE. In both cases, during the C-section, the EXIT technique was performed with a team of a neonatologist, a gyne cologist, an anesthesiologist, a pediatric surgeon, an otolaryngologist, a nurse, and a respiratory therapist. In both patients, the neonatologist achieved to secure the airway through orotracheal intubation at the first attempt. In the first case, lymphatic malformation was confirmed and re ceived sclerotherapy, and the second one was diagnosed with congenital hypothyroidism which was managed with levothyroxine. The patients needed invasive mechanical ventilation for 7 and 9 days, respectively, and were discharged without respiratory complications. CONCLUSIONS: In these patients, the EXIT technique was a safe procedure, carried out without inconvenience. A multi disciplinary approach and the availability of a neonatal intensive care unit are needed to reduce potential complications and ensure postnatal management. Timely prenatal diagnosis is essential to perform this technique.

Técnica EXIT como manejo de la vía aérea en masas gigantes congénitas de cuello / Ex-Utero Intrapartum Treatment for airway management in congenital giant neck masses

Resumen: Introducción: Las masas congénitas de cabeza y cuello se asocian a asfixia perinatal e injuria cerebral con elevada mortalidad. La técnica EXIT (Ex Útero Intrapartum Treatment) consiste en asegurar la vía aérea del neonato, sin interrumpir la oxigenación y perfusión materno-fetal a través del soporte placentario. Esta técnica no ha sido estandarizada en países de medianos ingresos. Objetivo: Describir el caso clínico de 2 neonatos manejados mediante la técnica EXIT. Caso Clínico: Se reportan dos casos, uno con malformación linfática diagnosticada a la semana 20 gestación y el segundo con tiromegalia y polihidramnios diagnosticados a la semana 35 de gestación. En ambos casos, duran te la cesárea se realizó la técnica EXIT con un equipo conformado por neonatólogo, ginecólogo, anestesiólogo, cirujano pediatra, otorrinolaringólogo, enfermero y terapeuta respiratorio. En los dos pacientes se logró asegurar la vía aérea mediante intubación orotraqueal al primer intento. En el caso 1 se confirmó la malformación linfática y recibió escleroterapia, y en el caso 2 se diagnosticó hipotiroidismo congénito asociado a bocio, que fue manejado con levotiroxina. Los pacientes se mantuvieron 7 y 9 días con ventilación mecánica invasiva respectivamente y egresaron sin complicaciones respiratorias. Conclusiones: La técnica EXIT en estos casos fue un procedimiento seguro, llevado a cabo sin inconvenientes. Se necesita un equipo multidisciplinario y la disponibilidad de una unidad de cuidados intensivos neonatales, con el objetivo de reducir potenciales complica ciones y garantizar el manejo postnatal. Para lograr su ejecución, es indispensable el diagnóstico prenatal oportuno.

Abstract: Introduction: Congenital head and neck masses are associated with perinatal asphyxia and brain injury, increasing the risk of death. The EXIT (Ex Utero Intrapartum Treatment) technique con sists of ensuring the newborn's airway while is still receiving placental support. This technique has not been standardized in developing countries. Objective: To describe the clinical outcomes of two infants who underwent the EXIT technique. Clinical Case: We present two cases, one with lymphatic malformation diagnosed at 20 weeks of gestational age (WGE) and the second one, a preterm newborn with thyromegaly and polyhydramnios, diagnosed at 35 WGE. In both cases, during the C-section, the EXIT technique was performed with a team of a neonatologist, a gyne cologist, an anesthesiologist, a pediatric surgeon, an otolaryngologist, a nurse, and a respiratory therapist. In both patients, the neonatologist achieved to secure the airway through orotracheal intubation at the first attempt. In the first case, lymphatic malformation was confirmed and re ceived sclerotherapy, and the second one was diagnosed with congenital hypothyroidism which was managed with levothyroxine. The patients needed invasive mechanical ventilation for 7 and 9 days, respectively, and were discharged without respiratory complications. Conclusions: In these patients, the EXIT technique was a safe procedure, carried out without inconvenience. A multi disciplinary approach and the availability of a neonatal intensive care unit are needed to reduce potential complications and ensure postnatal management. Timely prenatal diagnosis is essential to perform this technique.

Comparison of the efficacy of two surgical procedures on adenoidal hypertrophy in children.

OBJECTIVE: The aim of this study was to explore the treatment effects of two surgical procedures, performed with nasal endoscopy, on treating adenoidal hypertrophy in children. METHODS: A total of 100 children diagnosed with adenoidal hypertrophy were treated with curettage combined with microwave thermocoagulation and with low-temperature plasma radiofrequency ablation under nasal endoscopic guidance; 6 months after surgery, the effects on snoring, nasal congestion, hearing loss, and gland residue were retrospectively analyzed. RESULTS: Differences in snoring and hearing loss between the two groups were not statistically significant (P>0.05), but the differences in nasal congestion and gland residue between the two groups were statistically significant (P<0.05); the therapeutic effect was superior in the low-temperature plasma radiofrequency ablation group than in the curettage combined with microwave thermocoagulation group. CONCLUSION: Low-temperature plasma radiofrequency ablation with nasal endoscopy can achieve a better comprehensive effect on treating adenoidal hypertrophy in children than curettage combined with microwave thermocoagulation.

Treatment of Hypertrophic Granulation Tissue: A Literature Review.

BACKGROUND: Hypertrophic granulation tissue (HGT) is an uncommon but a frustrating complication of wound healing. Given its low prevalence and often refractory nature, many treatment options have been explored. OBJECTIVE: No comprehensive review exists on HGT management in dermatology literature; thus, the authors hope to compile a review of available treatments. MATERIALS AND METHODS: An exhaustive key word search of 3 databases was performed for treatment of HGT. Results from these reports were summarized in this review. RESULTS: Methods of treatment included silver nitrate, topical steroids (n = 11), intralesional steroids (n = 55), steroid tape (n = 25), surgical removal, polyurethane foam dressing (n = 32), and pulsed-dye laser (n = 13). CONCLUSION: With all treatment methods, the cases and studies reported varying degrees of successful treatment with HGT reduction. Given the lack of published literature, it remains unknown whether the initial injury preceding HGT formation determines treatment modality success. For HGT refractory to silver nitrate, choice of treatment depends on accessibility, ease of use, cost, and location of the wound. Intralesional and topical steroids should both be considered. Polyurethane foam can be considered an adjunct treatment. If resources allow, laser treatment should also be considered.

Botulinum Toxin Injections for Masseter Reduction in East Asians.

BACKGROUND: Cultural ideals for a slimmer face have led to an upsurge in interest in facial contouring among East Asians. Although surgical resection has traditionally been the main treatment option, botulinum toxin injection is becoming a popular, noninvasive alternative. OBJECTIVE: To describe the use of botulinum toxin injection for masseter reduction in East Asians. METHODS: An electronic search of the PubMed database was performed for studies published from 2000 to 2017 that meet the word combination of botulinum toxin, masseter, hypertrophy, and/or lower face contouring. Only the studies conducted in East Asian countries were analyzed in this review, exception of one study from Thailand. RESULTS: A total of 12 publications were identified. Each study was reviewed to extract relevant information on patient selection, injection techniques, efficacy, dosage, frequency, and main side effects of treating masseters with botulinum toxin. CONCLUSION: Botulinum toxin injection for masseter reduction in East Asians is efficacious and generally considered safe with no significant side effects. Future areas for investigation include defining the criteria for benign masseteric hypertrophy, minimum effective dosage of botulinum toxin, and the potential long-term effects of the injection.

Towards adulthood with a solitary kidney.

Around 1/1000 people have a solitary kidney. Congenital conditions mainly include multicystic dysplastic kidney and unilateral renal aplasia/agenesis; acquired conditions are secondary to nephrectomy performed because of urologic structural abnormalities, severe parenchymal infection, renal trauma, and renal or pararenal tumors. Children born with congenital solitary kidney have a better long-term glomerular filtration rate than those with solitary kidney secondary to nephrectomy later in life. Acute and chronic adaptation processes lead to hyperfiltration followed by fibrosis in the remnant kidney, with further risk of albuminuria, arterial hypertension, and impaired renal function. Protective measures rely on non-pharmacological renoprotection (controlled protein and sodium intake, avoidance/limitation of nephrotoxic agents, keeping normal body mass index, and limitation of tobacco exposure). Lifelong monitoring should include blood pressure and albuminuria assessment, completed by glomerular filtration rate (GFR) estimation in case of abnormal values. In the absence of additional risk factors to solitary kidney, such assessment can be proposed every 5 years. There is no current consensus for indication and timing of pharmacological intervention.

Cerebrospinal fluid leakage after turbinate submucosal diathermy: an unusual complication.

Submucosal diathermy of the inferior turbinate (SMDIT) is a generally safe procedure to control inferior turbinate hypertrophy. We present a case of a cerebrospinal fluid (CSF) leak at the craniocervical junction after SMDIT done in another institution. A 27-year-old man presented 3 weeks after undergoing SMDIT with signs and symptoms of meningitis and postnasal rhinorrhea. Nasal endoscopy and imaging revealed a nasopharyngeal CSF fistula at the craniocervical junction. Transnasal endoscopic repair and reconstruction was performed with no recurrence on repeat imaging and clinical follow up. We describe the first reported case in the literature of an iatrogenic CSF fistula caused by SMDIT, an unusual and potentially fatal complication, and its surgical management. SIMILAR CASES PUBLISHED: 0 CONFLICT OF INTEREST: None.

Unilateral hypertrophy of the labia minora: A case series.

Asymmetric hypertrophy of the labia minora is a variant of normal anatomy that has not been described in the pediatric dermatology literature. Although often asymptomatic, in some cases, it can cause functional, emotional, and psychological problems. We report the clinical characteristics and outcomes of four children who presented with unilateral labium minus hypertrophy. This case series aims to establish awareness of this condition among pediatric dermatologists and provide recommendations regarding management.

[Comparison between the effect of endoscopic-assisted low temperature plasma and electric planer on the treatment of adenoid hypertrophy: a Meta-analysis].

OBJECTIVE: To compare the effect of endoscopic-assisted low temperature plasma (ELTP) and electric planer (EP) on the treatment of adenoid hypertrophy.
 Methods: We searched China National Knowledge Infrastructure (CNKI), Wanfang Database, Weipu Database, Chinese Biomedical Literature (CMB), PubMed, Embase, Cochrane Database, and collected the randomized controlled studies regarding the effect of ELTP and EP on the treatment of adenoid hypertrophy from January 2007 to June 2016. Methodologies were used to evaluate the included studies, and Meta-analysis was performed by Revman 5.2.
 Results: Thirteen studies including 1 448 patients fulfilled the study requirement. Seven hundred and twenty-two patients were treated with ELTP, and 726 patients were treated with EP. The Meta-analysis showed: compared with EP, ELTP could improve the cure rare (OR=3.19, 95% CI 1.42 to 7.15, P=0.005), reduce the blood loss during surgery (MD=-20.35, 95% CI -20.84 to -19.87, P<0.001), shorten the operation time (MD=-15.71, 95% CI -18.06 to -12.17, P<0.001), and reduce the incidence of complications (OR=0.13, 95% CI 0.06 to 0.30, P<0.001), while there was no difference between the 2 groups in the postoperative residual rate of adenoid, postoperative hemorrhage rate and the rate of torus tubarius injury.
 Conclusion: Comparing with EP, ELTP shows more advantages in the adenoidectomy.

Effect of Roux-en-Y gastric bypass and diet-induced weight loss on diabetic kidney disease in the Zucker diabetic fatty rat.

BACKGROUND: Reductions in urinary protein excretion after Roux-en-Y gastric bypass (RYGB) surgery in patients with diabetic kidney disease have been reported in multiple studies. OBJECTIVES: To determine the weight loss dependence of the effect of RYGB on urinary protein excretion by comparing renal outcomes in Zucker diabetic fatty rats undergoing either gastric bypass surgery or a sham operation with or without weight matching. SETTING: University laboratories. METHODS: Zucker diabetic fatty rats underwent surgery at 18 weeks of age. A subgroup of sham operated rats were weight matched to RYGB operated rats by restricting food intake. Urinary protein excretion was assessed at baseline and at postoperative weeks 4 and 12. Renal histology and macrophage-associated inflammation were assessed at postoperative week 12. RESULTS: Progressive urinary protein excretion was attenuated by both RYGB and diet-induced weight loss, albeit to a lesser extent by the latter. Both weight loss interventions produced equivalent reductions in glomerulomegaly, glomerulosclerosis, and evidence of renal macrophage infiltration. CONCLUSION: Weight loss per se improves renal structure and attenuates renal inflammatory responses in an experimental animal model of diabetic kidney disease. Better glycemic control post-RYGB may in part explain the greater reductions in urinary protein excretion after gastric bypass surgery.

Risk Factors for Complications after Reduction Mammoplasty: A Meta-Analysis.

BACKGROUND: Reduction mammoplasty (RM) is a proven method of treating macromastia, but the risk factors for postoperative complications have not been clearly identified. Through this meta-analysis, the authors aimed to identify the risk factors of RM complications. METHODS: An extensive search of the literature describing complications after RM was performed using the PubMed Central, Embase, and Cochrane databases. The following risk factors were extracted: age, body mass index (BMI), tissue resection weight per breast (TRW), smoking and radiation therapy. Odds ratios (OR) were pooled with 95% confidence intervals (CI) to evaluate the relationship between these risk factors and complications after RM. RESULTS: A total of 16 unique studies including 10 593 patients were included in the final analysis. It showed that there was a significant difference in complications in BMI ≥30 kg/m2 (OR 0.73; 95% CI: 0.61-0.89, p = 0.001) and smoking (OR 1.56; 95% CI: 0.98-2.49, p = 0.06). Infection in those with BMI ≥30 kg/m2 showed a significant difference (OR 0.68; 95% CI: 0.52-0.89, p = 0.004), as well as wound dehiscence in smokers (OR 2.73; 95% CI: 1.60-4.67, p = 0.0002) and infection in irradiated breasts (OR 20.38; 95% CI: 3.42-121.35, p = 0.0009). However, there was no significant difference in age ≥50 years (OR 0.96; 95% CI: 0.71-1.29, p = 0.78), combined TRW ≥1000 g (OR 1.04; 95% CI: 0.43-2.50, p = 0.93). CONCLUSIONS: BMI ≥30 kg/m2 and smoking increase the risk of complications. Persons who are obese or irradiated are more likely to develop infections, and smokers experienced a higher incidence of wound dehiscence than did nonsmokers. However, patients aged ≥50 years and TRW ≥1000 g are not associated with complications from RM.

Virginal Breast Hypertrophy: Different Presentations of 2 Cases and the Role of Tamoxifen as an Adjuvant Therapy.

BACKGROUND: Virginal breast hypertrophy is a rapid and massive enlargement of one or both breasts. There are several proposed causes and treatment options for virginal breast hypertrophy, but the investigations to support these theories are lacking. CASES: We report two premenarchal girls with virginal breast hypertrophy who presented as different clinical cases. After their surgical interventions, their clinical courses were followed for more than 2 years with tamoxifen as an adjuvant therapy. SUMMARY AND CONCLUSION: Breast size and shape disorders can be a disturbing cosmetic problem for adolescents who worry about their body image. A combination treatment of breast reduction surgery and tamoxifen is reasonable and can eliminate the need for repeated surgeries for girls with virginal breast hypertrophy.