Fibromyalgia is characterized by chronic widespread pain, fatigue, and sleep disturbances. Recent theories attribute fibromyalgia to central sensitization syndromes, suggesting altered nociceptive ...processing leads to hyperalgesia and allodynia. Standardized effective treatments are currently lacking. Palmitoylethanolamide and melatonin have shown pain-relieving effects in chronic pain conditions, including fibromyalgia, with excellent safety. Our open-label study assessed the impact of a daily combination of 1200 mg of palmitoylethanolamide and 0.2 mg of melatonin on pain, sleep, and quality of life in fibromyalgia patients. Between June 2023 and March 2024, 50 patients (2016 ACR criteria) were treated and evaluated at baseline, 1 month, 3 months, and 4 months (1 month discontinuation). The assessments included VAS for pain, ISI for insomnia, HAQ for health assessments, and a tender points evaluation. The patients, averaging 54.12 years old with a 3:1 female-to-male ratio, showed significant improvements in VAS, ISI, and HAQ scores relative to their own baselines and a reduction in tender points at 1 and 3 months, which was maintained at 4 months. No adverse events were reported. This study is the first to demonstrate the efficacy of a palmitoylethanolamide and melatonin combination as an adjunct therapy in fibromyalgia, highlighting its potential to reduce pain and improve sleep and quality of life.
Lymphedema is a progressive disease that negatively affects body image and physical, psychological, and social functions. There is lack of evidence in the present literature about the impact of super ...microsurgical lymphaticovenular anastomosis (LVA) on health-related quality of life (HRQoL). The aim of this prospective study is to report the outcomes of patients' HRQoL after LVA for lower and upper extremities lymphedema.
Between September 2015 and February 2017, 74 patients with upper or lower limb lymphedema (ULL or LLL) underwent LVA at our center. Quality of life (QoL) was assessed by lymphedema QoL questionnaire (LyMQoL), which is a validated disease-specific instrument to measure the impact of lymphedema on patient's lives, covering four domains: function, body image, symptoms, and mood. All patients were evaluated preoperatively, 1 month after surgery, and every 3 months up to 1 year. Additionally, we evaluated the episodes of lymphangitis and the need for conservative therapy before and after surgery.
After a mean follow-up of 8.5 months (range: 2-21 months), we observed an increase of 2.3 points in the overall QoL average for upper limb and 2.6 points for lower limb (
< 0.001). A statistically significant improvement in all four domains (
< 0.01) was reported after surgery, being present from the first postoperative months for both upper and lower extremities.
Our study shows that lymphaticovenular anastomosis improves HRQoL in patients affected by ULL and LLL. Additionally, both a reduction of episodes of lymphangitis and a decrease in the need of conservative therapy were observed in this cohort of patients.
Objective
Groin dissection is the procedure with the highest risk of lower limb lymphedema.As lymph stasis causes irreversible alterations to the limb over time,therapies should be administered in ...early stages,or better yet, lymphatic drainage impairment should be prevented.We developed a new preventive approach to lymphedema after groin dissection, and we report our preliminary experience.
Patients and Methods
We enrolled 5 patients undergoing bilateral groin dissection for vulvar cancer. Preoperative study of lower limbs lymphatic function was obtained by lymphoscintigraphy, with lymphatic transport index, indocyanine green (ICG) lymphography, and volume measurement with lower extremity lymphedema (LEL) index calculation. At the end of lymphadenectomy, one groin was closed in the standard way. On the other side, a lymphatic flap pedicled on the distal perforator of the deep branch of the superficial circumflex iliac vessels, was transposed into the groin region. Lymphatic function examination of the limbs was repeated 6 months after surgery.
Results
Before surgery no patient showed lymphatic drainage impairment at lymphoscintigraphy or lymphography, LEL index was in every limb lower than 250 (mean: 217.3 ± 13.83). After surgery the limbs treated with the flap showed no pathological swelling, LEL‐index < 250 (mean: 235.4 ± 13.069), linear pattern at lymphography, and normal lymphoscintigraphy. The untreated limbs showed from moderate to severe edema with 265 < LEL‐index < 310 (mean: 283 ± 16.3), diffuse dermal backflow at lymphography and interruption of lymph flow, with dermal backflow, at lymphoscintigraphy. Mean difference between preoperative and postoperative volumes was 64.8 ± 25.1 in the untreated side and 19 ± 11.7 in the side with the flap. The difference between preoperative and postoperative volumes compared between the treated and untreated side was statistically significant (P < .01).
Conclusion
Our preliminary evidence suggests that this flap can prevent lymphedema after groin dissection. Further studies are necessary to confirm these results.
To compare the efficacy of adalimumab (ADA) and infliximab (IFX) in patients with non-infectious intermediate uveitis, posterior uveitis, and panuveitis. Demographic, clinical, instrumental, and ...therapeutic data from patients enrolled were collected at the start of treatment, at 12-month follow-up, and at the last follow-up assessment. One hundred seven patients (46 females, 187 eyes) were enrolled, 66 (61.7%) treated with ADA and 41 (38.3%) with IFX. Bilateral involvement was observed in 80 cases. The mean follow-up was 26.45 ± 21.71 months for ADA patients and 56.60 ± 56.04 months for IFX patients. The overall decrease of uveitis frequency during the first 12 months of treatment was 66.7% in the IFX group and 84.2% in the ADA group, compared to the previous 12 months (
p
= 0.09). A significantly higher corticosteroid dosage was found among patients treated with ADA at the last follow-up visit (
p
= 0.008). The percentage of patients co-administered with corticosteroids was significantly higher among ADA patients both at the 12-month visit (
p
= 0.03) and at the last visit (
p
= 0.0004). The frequency of uveitic macular edema (UME) was significantly higher among patients treated with ADA compared to those treated with IFX at the 12-month assessment (
p
= 0.015) and at the last follow-up visit (
p
= 0.011); central macular thickness was significantly higher in ADA group compared to the IFX group at the last follow-up assessment (
p
= 0.04). ADA and IFX have shown a similar efficacy in controlling uveitis relapses, but IFX showed a more pronounced corticosteroid sparing effect and a significantly higher capacity in resolving UME compared to ADA.
Background
Additional prognostic factors and personalized therapeutic alternatives for vulvar squamous cell carcinoma (VSCC), especially for advanced stages with poor prognosis, are urgently needed.
...Objectives
To review and assess literature regarding underlying molecular mechanisms of VSCC target therapeutic and prognostic approaches.
Methods
We performed a narrative literature review from the inception of the database up to January 2020 limited to English language, organizing knowledge in five main fields: extracellular and intracellular cell cycle deregulation, tumor immune microenvironment, tumor angiogenesis and hormones.
Results
EGFR immunohistochemical overexpression/gene amplification, representing early events in VSCC carcinogenesis, have been correlated with a worse prognosis and led to inclusion of erlotinib in cancer guidelines. p16 expression and HPV positivity are linked to a better prognosis, while p53 overexpression is linked to a worse prognosis; thus, biomarkers could help tailoring conventional treatment and follow-up. The implications of PD-L1 positivity in reference to HPV status and prognosis are still not clear, even though pembrolizumab is part of available systemic therapies. The role of tumor angiogenesis emerges through data on microvessel density, immunohistochemical VEGF staining and evaluation of serum VEGF concentrations. Few data exist on hormonal receptor expression, even though hormonal therapy showed great manageability.
Conclusions
We suggest adding p16, p53 and HPV status to routine hystopathological examination of vulvar biopsies or surgical specimens. Predictive biomarkers for anti-EGFR and anti-PD-1/PD-L1 drugs are needed. Enough preclinical data supporting anti-angiogenic target therapies in clinical trials are existing. Hormonal receptor expression deserves further investigation.
Surgical treatment is the gold standard of care for vulvar cancer and is burdened by a high risk of wound complications due to the poor healing typical of the female genital area. Moreover, this ...malignancy has a high risk of local relapse even after wide excision. For these reasons, secondary reconstruction of the vulvoperineal area is a relevant and challenging scenario for gynecologists and plastic surgeons. The presence of tissue already operated on and undermined, scars, incisions, the possibility of previous radiation therapy, contamination of urinary and fecal pathogens in the dehiscent wound or ulcerated tumor, and the unavailability of some flaps employed during the primary procedure are typical complexities of this surgery. Due to the rarity of this tumor, a rational approach to secondary reconstruction has never been proposed in the literature.
In this observational retrospective study, we reviewed the clinical data of patients affected by vulvar cancer who underwent secondary reconstruction of the vulvoperineal area in our hospital between 2013 and 2023. Oncological, reconstructive, demographic, and complication data were recorded. The primary outcome measure was the incidence of wound complications. The secondary outcome measure was the indication of the different flaps, according to the defect, to establish an algorithm for decision-making.
Sixty-six patients were included; mean age was 71.3 ± 9.4 years, and the mean BMI was 25.1 ± 4.9. The mean size of the defect repaired by secondary vulvar reconstruction was 178 cm
± 163 cm
. Vertical rectus abdominis myocutaneous (VRAM), anterolateral thigh (ALT), fasciocutaneous V-Y (VY), and deep inferior epigastric perforator (DIEP) were the flaps more frequently employed. We observed five cases of wound breakdown, one case of marginal necrosis of an ALT flap, and three cases of wound infection. The algorithm we developed considered the geometry and size of the defect and the flaps still available after previous surgery.
A systematic approach to secondary vulvar reconstruction can provide good surgical results with a low rate of complications. The geometry of the defect and the use of both traditional and perforator flaps should guide the choice of the reconstructive technique.
To create a comprehensive algorithmic approach to reconstruction after vulvar cancer ablative surgery, which includes both traditional and perforator flaps, evaluating anatomical subunits and shape ...of the defect.
We retrospectively reviewed 80 cases of reconstruction after vulvar cancer ablative surgery, performed between June 2006 and January 2016, transferring 101 flaps. We registered the possibility to achieve the complete wound closure, even in presence of very complex defects, and the postoperative complications. On the basis of these experience, analyzing the choices made and considering the complications, we developed an algorithm to help with the selection of the flap in vulvoperineal reconstruction after oncologic ablative surgery for vulvar cancer.
We employed eight types of different flaps, including 54 traditional fasciocutaneous V-Y flaps, 23 rectus abdominis myocutaneous flaps, 11 anterolateral thigh flaps, three V-Y gracilis myocutaneous flaps, three free style perforators V-Y flaps from the inner thigh, two Limberg flaps, two lotus flaps, two deep inferior epigastric artery perforator flap, and one superficial circumflex iliac artery perforator flap. The structures most frequently involved in resection were vulva, perineum, mons pubis, groins, vagina, urethra and, more rarely, rectum, bladder, and lower abdominal wall.
The algorithm we implemented can be a useful tool to help flap selection. The key points in the decision-making process are: anatomical subunits to be covered, overall shape and symmetry of the defect and some patient features such as skin laxity or previous radiotherapy. Perforator flaps, when feasible, must be considered standard in vulvoperineal reconstruction, although in some cases traditional flaps remain the best choice.
A few studies have reported the safety profile of interleukin (IL)-1 blockers from real life. The aim of this study is to describe anakinra (ANA) and canakinumab (CAN) safety profile in children and ...adults, based on data from a real-life setting. Demographic, clinical, and therapeutic data from patients treated with ANA and CAN were retrospectively collected and analyzed. Four hundred and seventy five patients were enrolled; ANA and CAN were prescribed in 421 and 105 treatment courses, respectively. During a mean follow-up of 24.39 ± 27.04 months, 89 adverse events (AE) were recorded; 13 (14.61%) were classified as serious AE (sAE). The overall estimated rate of AE and sAE was 8.4 per 100 patients/year. Safety concerns were more frequent among patients aged ≥ 65 years compared with patients < 16 years (
p
= 0.002). No differences were detected in the frequency of safety concerns between monotherapy and combination therapy with immunosuppressants (
p
= 0.055), but a significant difference was observed when injection site reactions were excluded from AE (
p
= 0.01). No differences were identified in relation to gender (
p
= 0.462), different lines of biologic therapy (
p
= 0.775), and different dosages (
p
= 0.70 ANA;
p
= 0.39 CAN). The overall drug retention rate was significantly different according to the occurrence of safety concerns (
p
value < 0.0001); distinguishing between ANA and CAN, significance was maintained only for ANA (
p
< 0.0001 ANA;
p >
0.05 CAN). Treatment duration was the only variable associated with onset of AE (OR = 0.399 C.I. 0.250–0.638,
p
= 0.0001). ANA and CAN have shown an excellent safety profile; the risk for AE and sAE tends to decrease over time from the start of IL-1 inhibition.
Inguinofemoral lymphadenectomy, frequently performed for vulvar cancer, is burdened with substantial immediate and long-term morbidity. One of the most disabling treatment-related sequelae is lower ...limb lymphedema (LLL). The present study aims to describe the wound complications and the severity of LLL in patients who have undergone groin dissection for vulvar cancer and immediate inguinal reconstruction with the Lymphatic Superficial Circumflex Iliac Perforator flap (L-SCIP). We retrospectively reviewed the data of patients who underwent bilateral groin dissection and unilateral inguinal reconstruction with the L-SCIP. The presence and severity of postoperative LLL during the follow-up period were assessed by lymphoscintigraphy and limbs' volume measurement. In addition, immediate complications at the level of the inguinal area were registered. The changes between preoperative and postoperative limb volumes were analyzed by Student's
test.
values < 0.05 were considered significant. Thirty-one patients were included. The mean variation of volume was 479 ± 330 cc3 in the side where groin reconstruction had been performed, and 683 ± 425 cc3 in the contralateral side, showing smaller variation in the treated side (
= 0.022). Lymphoscintigraphy confirmed the clinical findings. Based on our results, inguinal reconstruction with L-SCIP performed at the same time of groin dissection in patients treated for vulvar cancer can provide a significant protective effect on LLL.
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