Dermato-Radiological Evaluation of Congenital Limb Overgrowth Vascular Syndromes.

International Society for the Study of Vascular Anomalies classification defines Congenital Limb Overgrowth Vascular Syndromes (CLOS) as a subset of vascular syndromes with other abnormalities that present with unilateral limb overgrowth. It includes Klippel-Trenaunay Syndrome, Parkes-Weber Syndrome, CLOVES (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Spinal/Skeletal Anomalies/Scoliosis) Syndrome, Proteus Syndrome, PTEN Hamartomatous Syndrome, and Fibroadipose Vascular Anomaly. Due to their rare and complex nature, a multidisciplinary approach to diagnosis and treatment is required. A thorough clinical and radiological workup can go miles in reflecting on the patient's outcome. Here we report five cases of CLOS with their detailed dermato-radiological profiles.

Epidural lipomatosis with foci of hemorrhage and acute compression of the spinal cord in a child with CLOVES syndrome: illustrative case.

BACKGROUND: Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies, and/or scoliosis (CLOVES) syndrome is the most recently described combined vascular anomaly characterized by congenital excessive growth of adipose tissue, vascular malformations, epidermal nevi, and skeletal deformities. This condition exhibits a significant variability in clinical manifestations and a tendency for rapid progression and affects extensive anatomical regions. Information regarding the association of epidural lipomatosis with low-flow venous lymphatic malformations is rare, with few reports in the literature. OBSERVATIONS: The authors present a case of a 6-year-old girl who was admitted to the emergency department complaining of rapidly progressing weakness in her lower extremities and partial loss of sensation in the inguinal area. Radiologically, an extradural mass was identified at the T2-6 level, causing acute spinal cord compression. Urgent decompression and partial resection of the mass were performed. Despite satisfactory intraoperative hemo- and lymphostasis, postoperative lymphorrhea/seroma leakage was encountered as a delayed complication and was managed conservatively. LESSONS: CLOVES syndrome is characterized by the combination of various clinical symptoms, not all of which are included in the abbreviation, as well as a progressively deteriorating course, the emergence of new symptoms, and complications throughout the patient's life. This necessitates ongoing monitoring of such patients.

Monitoring Changes in Biochemical and Metabolite Profiles in Garlic Cloves during Storage.

Storage is important for the garlic cloves industry because it is critical to enabling a year-round supply. This study aimed to investigate the changes in biochemical and metabolic profiles in garlic cloves in terms of different temperatures and cultivars during storage using nontargeted and targeted metabolomics. The results showed that the storage temperatures and times were important factors affecting the composition and metabolite content of garlic cloves. In detail, the metabolic profiling of garlic cloves changed significantly at 22 °C, which was mainly related to sprouting. Furthermore, γ-glutamyl peptide was converted into the corresponding flavor precursors or free amino acids, leading to the fluctuation in the amount of nutrients in garlic cloves. In contrast, the quality of garlic cloves remained stable for 290 days at 0 °C though metabolism still occurred, which indicated that the slight chemical changes did not impact the quality significantly and low temperature could prolong their dormancy.

The Practicality of Preparing Skim Breast Milk at Home for Treatment of Infants Requiring Low Fat Diets.

Introduction: The benefits of breast milk (BM) for infants have long been established. However, for health-compromised infants with difficulty processing long-chain triglycerides, BM is often discontinued, and skimmed breast milk (SBM) is used as a dietary treatment. SBM is usually produced for inpatients in a hospital laboratory. The aim of this study was to determine the viability of skimming BM at home. Case Report: A female infant was diagnosed with congenital lipomatous asymmetric overgrowth, vascular malformations, epidermal nevi, and skeletal and spinal anomalies (CLOVES) syndrome, with symptoms of lymphatic malformation, chylothorax, and pleural effusion. The patient's family produced SBM at home after discharge; the SBM met the dietary treatment requirements and kept symptoms under control. Methods: A nonrefrigerated benchtop centrifuge was used to produce SBM at the patient's home. The optimal setting for the centrifuge was determined and then used to process BM samples from the infant's mother. The samples were randomly selected from each 10-day period over 6 months, and 18 samples were processed in total. The hospital laboratory processed the same samples of BM and analyzed the macronutrients with a comparison of the home-produced SBM to the hospital-produced SBM. Results: The home-produced SBM met the dietary treatment requirement of <1.0 g/dL of fat content. Fat was significantly lower, proteins were significantly higher, and carbohydrates and calories were not significantly different compared to hospital-produced SBM. Conclusions: It is viable to consistently produce SBM at home that meets the dietary treatment requirements of health-compromised infants.

Combined surgery and sclerotherapy for 13 years: a case report of a patient with CLOVES.

Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal anomalies (CLOVES) constitute a rare overgrowth disorder resulting from a mosaic function-acquiring mutation in the PIK3CA gene. Targeted drugs for the PI3K-AKT signaling pathway remain under clinical trial and surgery is commonly used to meet both aesthetic and functional requirements for CLOVES patients. We report here the course and experience of a male patient treated at our institution for up to 13 years. The course of treatment consisted of nine anhydrous ethanol sclerotherapy procedures and two segmental trunk mass resections. After undergoing sequential treatment, the patient experienced improved thoracic deformity and scoliosis, enabling him to grow and develop normally.

Whole-genome sequencing of four culturable endophytic bacteria from German hardneck garlic cloves (Allium sativum L.).

We present the whole-genome sequence of four bacterial endophytes associated with German hardneck garlic cloves (Allium sativum L.). Among them, Agrobacterium fabrum and Pantoea agglomerans are associated with plant protection, while Rahnella perminowiae and Stenotrophomonas lactitubi are pathogens. These data will facilitate the identification of genes to improve garlic.

Alpelisib: A Novel Agent for PIK3CA-Related Overgrowth Spectrum.

The aim of this review is to present the information a clinician will need when considering alpelisib therapy for a patient diagnosed with PIK3CA-related overgrowth spectrum (PROS). PROS is a condition caused by a somatic recessive gain-of-function mutation in the gene encoding phosphatidylinositol-3-kinase (PI3K). PROS is rare, affecting approximately 14 births per 1 million. PROS affects many different tissues including skin, bone, vascular, adipose, and connective tissues, thus its presentations vary widely. The presentation of PROS is often described as mosaic, as the disease typically does not affect all cells in the body. For patients two years of age and older requiring systemic therapy, alpelisib is an option which was recently granted accelerated approval by the US Food and Drug Administration (FDA) on April 5, 2022. Alpelisib is an inhibitor of PI3K, slowing the progression of existing lesions and preventing new lesions in patients with PROS. Important drug interactions exist with both CYP3A4 inducers and CYP2C9 substrates. Additionally, providers of patients receiving alpelisib should be aware of potential side effects including hypersensitivity, severe cutaneous adverse reactions, hyperglycemia, pneumonitis, diarrhea, and embryo-fetal toxicity. Despite the potential for adverse events, alpelisib has provided clinical benefit to many patients with PROS as evidenced by the current literature. This review collects and summarizes the currently available evidence, including a recently published case series and multiple case reports. Alpelisib is a promising new option for patients with PROS.

PIK3CA-related overgrowth spectrum (PROS): a rare case report.

Case report. Introduction and Importance: The purpose of this study is to report an extremely rare case of PIK3CA-related overgrowth spectrum. Case Presentation: A 12-year-old boy presented with severe overgrowth in the left lower limb causing severe movement restriction and decreased quality of life. Interventions and Outcome: Episodes of myiasis were manually treated through mechanical removal and the patient was placed on rapamycin therapy for managing vascular malformations. Conclusion: CLOVES syndrome is a rare overgrowth disorder that can be confused with other overgrowth syndromes; however, clinical and imaging findings are essential for pinpointing the correct diagnosis as genetic sequencing may not always prove reliable.

Gastrointestinal Manifestations of CLOVES Syndrome.

Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/skeletal/spinal anomalies (CLOVES) is a recently recognized syndrome. It is caused by somatic mutations in the PIK3CA gene that regulates cell growth and division. Although gastrointestinal manifestations of other PIK3CA-associated disorders have been described, they have not been well-characterized in CLOVES syndrome. We present a case report of a 34-year-old man with an established diagnosis of CLOVES syndrome who underwent a diagnostic colonoscopy for hematochezia and colonic wall thickening on imaging. Colonoscopy revealed widespread variceal-like submucosal lesions. Computed tomography/angiography showed the absence of the inferior mesenteric vein, impairing venous drainage.

Ultrasound-Guided Percutaneous Intercostal Cryoneurolysis for Acute-on-Chronic Pain in CLOVES Syndrome.

Cryoneurolysis is an analgesic method that has been shown to provide extended pain relief in postoperative patients. However, to date, this method has not been described in nonsurgical inpatients with chronic pain experiencing an acute exacerbation. This analgesic modality has the potential to provide pain relief for patients whose expected duration of severe acute pain would outlast that of other regional anesthetic techniques while avoiding opioid escalation and facilitating discharge. We present a patient with acute exacerbation of chronic pain from breast ulcerations caused by congenital lipomatous overgrowth, vascular malformations, epidermal nevis, spinal/skeletal anomalies/scoliosis (CLOVES) syndrome that was successfully treated as an inpatient with a portable cryoneurolysis device.  This is the first reported use of cryoneurolysis in an inpatient setting to treat acute-on-chronic pain in a nonsurgical patient. The authors recommend regional anesthesiologists and acute pain specialists to utilize this technique to provide analgesia in patients with complex pain to facilitate hospital throughput.

Response to sirolimus in capillary lymphatic venous malformations and associated syndromes: Impact on symptomatology, quality of life, and radiographic response.

BACKGROUND: Capillary lymphatic venous malformations (CLVM) and associated syndromes, including Klippel-Trenaunay syndrome (KTS) and congenital lipomatous overgrowth, vascular malformation, epidermal nevi, skeletal, and spinal syndrome (CLOVES), are underrecognized disorders associated with high morbidity from chronic pain, recurrent infections, bleeding, and clotting complications. The rarity of these disorders and heterogeneity of clinical presentations make large-scale randomized clinical drug trials challenging. Identification of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [gene]) mutations in CLVM has made targeted medications, such as sirolimus, attractive treatment options. The aim of this study was to investigate the safety and efficacy of sirolimus therapy in CLVM. PROCEDURE: A combined prospective and retrospective cohort of pediatric and young adult patients with CLVM treated with sirolimus was evaluated for disease response, including symptom improvement, quality of life (QOL), and radiologic response. Sirolimus dosing regimens and toxicities were also assessed. RESULTS: Twenty-nine patients with CLVM, including KTS and CLOVES, were included. Ninety-three percent of patients reported improved QOL, and 86% had improvement in at least one symptom. Most significantly, improvement was noted in 100% of patients with bleeding and 89% with thrombotic complications with corresponding decreases in mean D-dimer (p = .008) and increases in mean fibrinogen (p = .016). No patients had progressive disease on sirolimus. Most common side effects included neutropenia, lymphopenia, infection, and aphthous ulcers/stomatitis. No toxicities were life-threatening, and none required long-term discontinuation of sirolimus. CONCLUSION: Sirolimus appears to be effective at reducing complications and improving QOL in patients with CLVM and associated syndromes. In this patient cohort, sirolimus was well tolerated and resulted in few treatment-related toxicities.

Case report: a step-by-step body contouring approach in a case of young patient with CLOVES syndrome.

CLOVES syndrome is a rare overgrowth disorder caused by gene mutations. This case study describes a 28-year-old woman with CLOVES syndrome who underwent multiple surgeries to achieve a positive outcome while preserving lymphovascular structures. The report underscores the importance of a multidisciplinary approach and tailored surgical interventions for managing CLOVES.

Regulation of the Gut Microbiota and Inflammation by ß-Caryophyllene Extracted from Cloves in a Dextran Sulfate Sodium-Induced Colitis Mouse Model.

Ulcerative colitis is an inflammatory bowel disease characterized by symptoms such as abdominal pain, diarrhea, bleeding, and weight loss. Ulcerative colitis is typically treated with anti-inflammatory drugs; however, these drugs are associated with various side effects, limiting their use. ß-Caryophyllene (BCP), a natural compound derived from cloves, has antioxidant, antibacterial, and anti-inflammatory activities. In this study, we aimed to investigate the effects of BCP on colitis in a dextran sulfate sodium (DSS)-induced colitis mouse model. BCP was administered for seven days, followed by 2.5% DSS for additional seven days to induce colitis. Changes in stool weight, recovery of gut motility, colon length, colon histology, myeloperoxidase activity, inflammatory cytokines (TNF-α, IL-1ß, IL-6, IgA, and IgG), and the gut microbiota were observed. Administration of BCP increased stool weight, restored gut motility, and considerably increased colon length compared to those in the untreated colitis mouse model. In addition, the amount of mucin and myeloperoxidase activity in the colon increased, whereas the concentrations of IL-1ß, IL-6, and TNF-α decreased following the administration of BCP. Furthermore, BCP reduced the abundance of Proteobacteria which can cause intestinal immune imbalance. These results suggest that BCP has a potential to be developed as a preventive agent for colitis.

Antibacterial activity of essential oils extracted from the unique Chinese spices cassia bark, bay fruits and cloves.

Spices are widely used in daily life such as diet and have certain activity. Especially in China, spices have been mainly used as condiments for thousands of years in order to improve the sensory quality of food; in addition, they and their derivatives can also be used as preservatives. In this study, three spices with unique Chinese characteristics widely used were selected: cassia bark (bark of Cinnamomum camphora Presl), bay fruits (Laurus nobilis), and cloves (Syzygiumaromaticum). The main components and antibacterial ability of these three spices were analyzed by simulated extraction method. Through headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) analysis, it was determined that the main active compounds in the essential oils of cassia bark, bay fruits and cloves were cinnamaldehyde (78.11%), cinnamaldehyde (61.78%) and eugenol (75.23%), respectively. The agar plate diffusion test and the simulated food culture medium experiment confirmed that the essential oils extracted from the three flavors have antibacterial effects on Listeria monocytogenes, Listeria innocua, Listeria welshimeri, Listeria ivanovii, Listeria grayi and Vibrio parahaemolyticus. The antibacterial activity of different strains has different optimal extraction conditions. Generally speaking, cinnamon essential oil has the strongest antibacterial activity, while laurel fruit has the lowest antibacterial activity. The study proved the antibacterial activity of these three Chinese-specific spices and provided some new ideas and methods for the subsequent research and preparation of natural food additives and food antibacterial agents.

Use of intercostal nerve block for chest wall pain in a patient with CLOVES syndrome.

Congenital lipomatous overgrowth, vascular malformations, epidermal nevi and scoliosis/skeletal/spinal anomalies (CLOVES) syndrome is an extremely rare overgrowth syndrome characterized by complex vascular malformations. Management requires an interdisciplinary approach including debulking operations for tissue overgrowth, embolization therapy for vascular malformations and management of chronic pain due to congenital and recurrent vascular overgrowth and from scar tissue from surgical interventions. Here, we present a 35-year-old female with complex medical history due to CLOVES syndrome, with large vascular malformations on her chest, status post debulking/embolization previously and now with continued chronic nociceptive and neuropathic pain, largely due to the recurrent nature of vascular malformations, but now finding some relief with fluoroscopy-guided intercostal nerve blocks which she never experienced before.

Clinical and Molecular Spectrum of Sporadic Vascular Malformations: A Single-Center Study.

Sporadic vascular malformations (VMs) are a large group of disorders of the blood and lymphatic vessels caused by somatic mutations in several genes-mainly regulating the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways. We performed a cross-sectional study of 43 patients affected with sporadic VMs, who had received molecular diagnosis by high-depth targeted next-generation sequencing in our center. Clinical and imaging features were correlated with the sequence variants identified in lesional tissues. Six of nine patients with capillary malformation and overgrowth (CMO) carried the recurrent GNAQ somatic mutation p.Arg183Gln, while two had PIK3CA mutations. Unexpectedly, 8 of 11 cases of diffuse CM with overgrowth (DCMO) carried known PIK3CA mutations, and the remaining 3 had pathogenic GNA11 variants. Recurrent PIK3CA mutations were identified in the patients with megalencephaly-CM-polymicrogyria (MCAP), CLOVES, and Klippel-Trenaunay syndrome. Interestingly, PIK3CA somatic mutations were associated with hand/foot anomalies not only in MCAP and CLOVES, but also in CMO and DCMO. Two patients with blue rubber bleb nevus syndrome carried double somatic TEK mutations, two of which were previously undescribed. In addition, a novel sporadic case of Parkes Weber syndrome (PWS) due to an RASA1 mosaic pathogenic variant was described. Finally, a girl with a mild PWS and another diagnosed with CMO carried pathogenic KRAS somatic variants, showing the variability of phenotypic features associated with KRAS mutations. Overall, our findings expand the clinical and molecular spectrum of sporadic VMs, and show the relevance of genetic testing for accurate diagnosis and emerging targeted therapies.

In-Situ Comparative Study of Eucalyptus, Basil, Cloves, Thyme, Pine Tree, and Tea Tree Essential Oil Biocide Efficacy.

Bio-colonization is a dynamic and multiphasic process headed by microorganisms. Conventional treatments to process affected stone materials include chemical biocides, whose formulations are mainly composed of quaternary ammonium salts(QAs), reported to be toxic for human health, dangerous for the environment, and not biodegradable. Accordingly, novel green and eco-friendly products are a promising alternative to treat stone materials deteriorated by microorganism colonization. In this study, the efficacy of pure essential oils (EOs) and a mix of EOs was assessed in situ and compared to a conventional biocide based on QAs, and two commercially green products based on EOs, which were taken as references, through application on a mosaic located at the Archaeological Park of Ostia Antica (Rome). The EO biocide efficacy was analyzed by ultraviolet induced luminescence, spectro-colorimetry and bio-luminometry analyses while the possibility of their permanence on simulated substrate was studied by FTIR spectroscopy. It was observed by FTIR analysis, that EOs considered volatile can leave a residue after the application; typical fingerprint bands at about 2926, 1510, and 1455 cm-1 were recorded in the EO spectra. Every tested oil was confirmed to have a biocide action although minimal in relation to the most conventional products based on QAs. The synergy of the essential oils revealed positive results, showing a stronger biocide efficacy. Further investigation should be carried out to develop the method of application and study of essential oils on cultural heritage.

How we approach the diagnosis of a vascular anomaly.

Vascular anomalies represent a diverse group of complex disorders that can cause significant complications, including coagulopathies, pain, and decreased function. The diagnosis of vascular anomalies is often challenging due to heterogeneity of presenting phenotypes and overlapping clinical features with other pediatric conditions. Pediatric hematologists/oncologists (PHO) are uniquely positioned for an essential role in diagnosing, managing, and coordinating the multidisciplinary care required to maximize the quality of life of these patients. Here, we review the diagnostic approach involved in patients with vascular anomalies and utilize cases to highlight the challenges involved, and how PHOs can play a vital part in the care of these patients.