Non-cholera Vibrio spp. invasive infections in the summer following May 2023 flood disaster in Romagna, Italy: a case series.

Non-cholera Vibrio spp. includes ubiquitous organisms living in aquatic environments. Their occurrence is associated with global warming and meteorological disasters. In May 2023 the Romagna region, Italy, was affected by severe floods. In the following 15 weeks we observed 5 patients with invasive infections caused by V. vulnificus (3/5) and V. harveyi (2/5). All patients (median age 77 years) had medical comorbidities and shared exposure to seawater. Two patients needed surgery; 2 died. In conclusion, we observed an increased burden of Vibrio spp. invasive infections after May 2023 floods, affecting old patients with predisposing medical conditions.

Very Rapid Improvement in Extended Nitric Oxide Parameters Is Associated With Clinical and Functional Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Dupilumab.

BACKGROUND AND OBJECTIVE: Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. METHODS: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. RESULTS: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main RSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP.

Comparison between the high-definition 3D exoscope and the operating microscope in head and neck reconstruction.

The purpose of this study was to compare the three-dimensional (3D) operating exoscope (OE) with the conventional operating microscope (OM) in head and neck reconstruction. A retrospective cohort study was performed including 50 consecutive patients with no history of previous surgery or irradiation (32 male, 18 female; mean age 59.2 ± 13.3 years), who underwent free flap head and neck reconstruction using a 3D OE (n = 25; OE group) or conventional OM (n = 25; OM group). The mean total operative time was 8.0 ± 1.53 h in the OE group and 7.6 ± 1.52 h in the OM group (P = 0.86). The median (interquartile range) anastomosis time was 78.0 (63.0-91.5) minutes in the OE group and 90.0 (75.5-115.0) minutes in the OM group (P = 0.06). The final free flap survival rate was 100%. Only seven patients experienced a free flap reconstruction-related complication, and they were similarly distributed between the two groups (four in the OE group, three in the OM group; P = 0.68). Secondary outcomes (length of hospital stay, tracheostomy dependence, feeding tube dependence) were comparable in the two groups (P > 0.05). The 3D OE is a viable alternative to the conventional OM for performing standard head and neck free flap reconstructive procedures.

Effects of ospemifene on overactive bladder in postmenopausal women with vulvovaginal atrophy.

OBJECTIVE: Overactive bladder (OAB) is a complex and multifactorial syndrome associated with urinary frequency, urgency and incontinence. The menopause-associated hormonal changes play a role in the development of this condition. Vaginal estrogens are effective in improving OAB in postmenopausal women (PMW) with vulvovaginal atrophy (VVA). Ospemifene is a selective estrogen receptor modulator licensed for the treatment of VVA. This study aimed to evaluate the effects of ospemifene on OAB symptoms in PMW with VVA. METHODS: Forty PMW suffering from OAB and VVA received oral ospemifene (60 mg/day) for 12 weeks. All patients were assessed with a urodynamic study, a 3-day bladder diary and validated questionnaires (International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form [ICIQ-UI SF] and International Consultation on Incontinence Questionnaire - Overactive Bladder [ICIQ-OAB]) at enrollment and at the end of the study. RESULTS: Cytometric capacity, bladder compliance and verbal sensory threshold responses during bladder filling were improved after treatment. The voiding diary showed a significant reduction of daily voids, urge urinary incontinence episodes and nocturnal events. The median overall scores of the ICIQ-UI and ICIQ-OAB were also significantly improved. CONCLUSIONS: Our study suggest that treatment with ospemifene in PMW suffering from OAB is associated with a reduction of OAB symptoms due to a decreased bladder sensitivity and with an improvement in quality of life.

Very rapid improvement of extended nitric oxide parameters, associated with clinical and functional betterment, in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) treated with Dupilumab.

BACKGROUND AND OBJECTIVE: Background: Dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, demonstrating a rapid onset of clinical effects. CRSwNP is characterized by an extended type-2 inflammatory involvement that can be assessed by extended nitric oxide analysis. Objective: In this study we investigated whether Dupilumab is associated with a rapid improvement in extended nitric oxide parameters, lung function and clinical outcomes in patients with CRSwNP. METHODS: : Consecutive patients with CRSwNP and indication to be treated with Dupilumab were evaluated for extended nitric oxide analysis (exhaled, FENO; bronchial, JawNO and alveolar, CalvNO components; nasal, nNO) and lung function 15 and 30 days after treatment initiation, and for clinical outcomes (nasal polyps score, NPS; quality of life questionnaires; visual analogue scales, VAS, for main symptoms, asthma control test, ACT) after 30 days of treatment initiation. RESULTS: 33 patients were enrolled. All extended nitric oxide and lung function parameters significantly improved after 15 days of treatment remaining stable at 30 days. NPS, VAS for main CRSwNP symptoms, quality of life questionnaires and ACT significantly improved after 30 days of treatment initiation. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway districts and this is associated with improved lung function and clinical parameters in patients with CRSwNP.

Umbilical Cord Mesenchymal Stromal Cells for Cartilage Regeneration Applications.

Chondropathies are increasing worldwide, but effective treatments are currently lacking. Mesenchymal stromal cell (MSCs) transplantation represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA) and rheumatoid arthritis (RA). Umbilical cord- (UC-) MSCs gained increasing interest due to their multilineage differentiation potential, immunomodulatory, and anti-inflammatory properties as well as higher proliferation rates, abundant supply along with no risks for the donor compared to adult MSCs. In addition, UC-MSCs are physiologically adapted to survive in an ischemic and nutrient-poor environment as well as to produce an extracellular matrix (ECM) similar to that of the cartilage. All these characteristics make UC-MSCs a pivotal source for a stem cell-based treatment of chondropathies. In this review, the regenerative potential of UC-MSCs for the treatment of cartilage diseases will be discussed focusing on in vitro, in vivo, and clinical studies.

Elective neck irradiation in the management of esthesioneuroblastoma: a systematic review and meta-analysis.

BACKGROUND: There is no consensus about the optimal management of the neck in clinically node negative esthesioneuroblastoma (ENB). The aim of this study is to assess the impact of elective neck irradiation (ENI) in terms of regional disease control and survival. METHODS: The study was performed according to the PRISMA guidelines searching on Scopus, PubMed/MEDLINE, and Google Scholar databases. The primary outcome was the regional recurrence rate (RRR), that was reported as odds ratio (OR) and 95% confidence interval (CI). Secondary outcomes were the overall survival (OS), and the distant-metastases free survival (DMFS), that were reported as logarithm of the hazard ratios (logHRs) and 95% confidence intervals (CIs). RESULTS: A total of 489 clinically node negative patients were included from 9 retrospective studies. ENI significantly reduced the risk of regional recurrence compared to no treatment. No difference was measured between ENI and observation, according to both OS and DMFS. No stratified analysis could be performed based on Kadish stage and Hyams grade. CONCLUSIONS: ENI should be recommended to improve the regional disease control. No advantage was measured in terms of survival or distant metastases with a low quality of evidence. Further prospective studies should be designed to understand if ENI could be avoided in early stage and low-grade tumors.

Menopause, aging and the failing pelvic floor: a clinician's view.

The management of pelvic organ disorders is common and challenging work. Nowadays, midlife women are more active than they were in the past, and the development of pelvic organ prolapse (POP) disrupts quality of life and impairs social and personal activities. The aging process and hormonal changes have a role in influencing the structure and function of the lower urinary and genital tract. Correct diagnosis of pelvic organ disorders and the identification of women's symptoms are the hallmarks of tailored management. Treatment is multimodal and multidisciplinary; it requires competence in pelvic medicine and surgery. When conservative treatments fail, women with symptomatic POP are candidates for reconstructive surgery: the optimal management requires clinicians who are familiar with all of the available strategies and who are able to choose the best strategies in a tailored manner. Knowing and understanding the management of POP should be integrated into the practice of health-care professionals dealing in menopause.

Thermal robustness of magnetic tunnel junctions with perpendicular shape anisotropy.

The concept of Perpendicular Shape Anisotropy STT-MRAM (PSA-STT-MRAM) has been recently proposed as a solution to enable the downsize scalability of STT-MRAM devices beyond the sub-20 nm technology node. For conventional p-STT-MRAM devices with sub-20 nm diameters, the perpendicular anisotropy arising from the MgO/CoFeB interface becomes too weak to ensure thermal stability of the storage layer. In addition, this interfacial anisotropy rapidly decreases with increasing temperature which constitutes a drawback in applications with a large range of operating temperatures. Here, we show that by using a PSA based storage layer, the source of anisotropy is much more robust against thermal fluctuations than the interfacial anisotropy, which allows considerable reduction of the temperature dependence of the coercivity. From a practical point of view, this is very interesting for applications having to operate on a wide range of temperatures (e.g. automotive -40 °C/+150 °C).

Cranberry, D-mannose and anti-inflammatory agents prevent lower urinary tract symptoms in women undergoing prolapse surgery.

Objective: We assessed the effect on lower urinary tract symptoms (LUTS) of a supplement containing cranberry, D-mannose and anti-inflammatory molecules in postmenopausal women undergoing surgery for cystocele.Study design: Forty postmenopausal women were randomized 1:1 to an active group receiving the nutritional supplement twice a day for 2 weeks starting from surgery, or to a control group receiving surgery only. Primary outcomes were the effectiveness in the postoperative LUTS and urinary tract infections (UTI). LUTS were investigated by a validated questionnaire (ICIQ-FLUTS) at baseline and at week 4. Secondary outcomes were the safety and tolerability of the supplement and other perioperative outcomes.Results: No significant differences were found in perioperative outcomes and in incidence of UTI. After surgery, women treated with the supplement experienced significantly better scores on the filling domain of the questionnaire. A non-significant decrease in voiding scores was also found. No adverse events were detected.Conclusion: The use of an oral supplement containing cranberry, D-mannose and anti-inflammatory molecules decreases the perception of LUTS in postmenopausal women after anterior colporraphy. Our data suggest that perioperative use of nutritional supplements may be useful in the management of postoperative LUTS.

Advances in surgical strategies for prolapse.

Pelvic floor dysfunctions are a complex condition in elderly women; pelvic organ prolapse, urinary or fecal incontinence, constipation, pelvic pain, and sexual dysfunction are common problems. The goal of surgical treatment is functional reconstruction with symptom management and repair of anatomic defects. The recent advancements in surgical treatment of pelvic floor dysfunction allow several good options for choosing the best surgery for each patient. The vaginal procedure is traditionally the gold standard approach for elderly patients, but abdominal surgery is increasing as a mini-invasive approach and the robotic approach is gaining acceptance for treatment of pelvic floor dysfunctions. In elderly individuals, a multitude of factors affects the final result of any reconstructive surgery such as postmenopausal or aging-associated changes in muscle tone and nerve function or changes in the function of the bladder or of the rectum: an understanding of the underlining functional status of pelvic organs is very important in aging women before proceeding to surgery. In this context, pelvic floor dysfunction, particularly in elderly women, should be addressed in a multidisciplinary manner and, at the forefront, centers for surgical planning could be helpful to perform safer, patient-tailored surgery.

Kaposi's sarcoma after T-cell costimulation blockade with abatacept in rheumatoid arthritis: a case report.

WHAT IS KNOWN AND OBJECTIVE: Kaposi's sarcoma (KS) is a malignant neoplasm caused by HHV-8, a pathogen that leads to endothelial cell transformation when host defences are weakened. CASE DESCRIPTION: Here we report the first case of KS during treatment with abatacept, a biologic agent targeting T-cell costimulation. The patient was a 64-year-old female with rheumatoid arthritis who developed multiple firm, purple-reddish nodules on the dorsal aspect of the right hand. Histological examination confirmed KS. WHAT IS NEW AND CONCLUSION: Although a direct causal relationship between KS development and abatacept treatment cannot be proved, we hypothesize a role for costimulation blockade.

On the antiquity of Legg-Calvé-Perthes disease: Skeletal evidence in Iron Age Italy.

Legg-Calvé-Perthes is a very rare disease involving childhood osteochondrosis of the femoral head due to interruption of its blood supply. The etiology is unknown. The signs of the pathology are well described in the literature but few paleopathological cases have been reported, mostly dating from Late Antiquity to Early Middle Ages. Here we report on morphometric and radiological analyses of a skeleton from the Etruscan necropolis of Spina (Ferrara, Italy, 6th-3rd century BCE), to our knowledge the most ancient case of Legg-Calvé-Perthes disease published thus far.

An observational study assessing peripheral neuropathy related to multiple myeloma.

We aimed at assessing the prevalence of peripheral neuropathy in newly diagnosed, treatment-naïve patients with multiple myeloma. We enrolled 153 patients with multiple myeloma at initial diagnosis. All patients underwent neurological examination and nerve conduction study. Patients with suspected pure small fiber neuropathy underwent skin biopsy. Of the 153 patients included in this study, 7.2 % had a multiple myeloma-related neuropathy. All patients suffered from a distal symmetric sensory peripheral neuropathy, associated with age (P = 0.04). Our study on prevalence rate of multiple myeloma-related peripheral neuropathy might provide a basis for improving the clinical management of this condition.

Selective steroid receptor modulators in reproductive medicine.

A key step forward in the treatment of hormone-dependent diseases has been made since the discovery of tissue-specific steroid receptor modulators (SRMs), or receptor ligands that elicit agonistic or antagonistic effects in a cell- and tissue-dependent manner. In reproductive medicine, selective estrogen receptors modulators (SERMs) and selective progesterone receptors modulator (SPRMs) were discovered and developed since the 1970s. SERMs were first released for the treatment of infertility and later developed in areas such as osteoporosis prevention and breast cancer treatment. The later discovery of SPRMs has provided molecules active on the inhibition of ovulation, on the endometrium and on leiomyoma cells, which are currently being developed for their antiproliferative effects in breast cancer and endometriosis. New molecules and new routes of administration of SERMs and SPRMs are in development for cancer treatment, long-term contraception and endometriosis. Based on the future advancements on the understanding of the mechanisms of action of these compounds, it is to be expected that future SRMs will emerge for newer indications.

Magnetic resonance imaging-quantified small bowel motility is a sensitive marker of response to medical therapy in Crohn's disease.

BACKGROUND: Magnetic resonance enterography (MRE) can measure small bowel motility, reduction in which reflects inflammatory burden in Crohn's Disease (CD). However, it is unknown if motility improves with successful treatment. AIM: To determine if changes in segmental small bowel motility reflect response to anti-TNFα therapy after induction and longer term. METHODS: A total of 46 patients (median 29 years, 19 females) underwent MRE before anti-TNFα treatment; 35 identified retrospectively underwent repeat MRE after median 55 weeks of treatment and 11 recruited prospectively after median 12 weeks. Therapeutic response was defined by physician global assessment (retrospective group) or a ≥3 point drop in the Harvey-Bradshaw Index (prospective group), C-reactive protein (CRP) and the MaRIA score. Two independent radiologists measured motility using an MRE image-registration algorithm. We compared motility changes in responders and nonresponders using the Mann-Whitney test. RESULTS: Anti-TNFα responders had significantly greater improvements in motility (median = 73.4% increase from baseline) than nonresponders (median = 25% reduction, P < 0.001). Improved MRI-measured motility was 93.1% sensitive (95%CI: 78.0-98.1%) and 76.5% specific (95% CI: 52.7-90.4%) for anti-TNFα response. Patients with CRP normalisation (<5 mg/L) had significantly greater improvements in motility (median = 73.4% increase) than those with persistently elevated CRP (median = 5.1%, P = 0.035). Individuals with post-treatment MaRIA scores of <11 had greater motility improvements (median = 94.7% increase) than those with post-treatment MaRIA score >11 (median 15.2% increase, P = 0.017). CONCLUSIONS: Improved MRI-measured small bowel motility accurately detects response to anti-TNFα therapy for Crohn's disease, even as early as 12 weeks. Motility MRI may permit early identification of nonresponse to anti-TNFα agents, allowing personalised treatment.

Extracorporeal membrane oxygenation as bridge to lung transplantation.

Lung transplantation (OLT) is a viable option for end-stage pulmonary diseases in selected patients with satisfactory long-term results. However, the paucity of available donors engenders a prolonged stay on the waiting list with progressive decline of lung function. In cases of sudden respiratory failure, admission to an intensive care unit with institution of extracorporeal membrane oxygenation (ECMO) may be an option while a waiting an emergency OLT. In 12 OLT candidates we started ECMO because of acute decline of lung function. Eleven patients had cystic fibrosis and the other subject, histiocytosis X. In 7 patients bilateral OLT was performed after a mean waiting time of 6 days from ECMO institution; 5 patients died on ECMO at a mean time of 11.6 days. After OLT 2 patients required reoperation for hemothorax; renal failure and acute leg ischemia occurred in 2 patients. The mean weaning time from ECMO after OLT was 2.14 days. No patient died in the perioperative period and 1-year survival was 85.7%. ECMO represents a valid option as a bridge to urgent OLT for selected candidates.

Forced expression of OCT4 influences the expression of pluripotent genes in human mesenchymal stem cells and fibroblasts.

Genetic reprogramming of adult cells to generate induced pluripotent stem (iPS) cells is a new and important step in sidestepping some of the ethical issues and risks involved in the use of embryonic stem cells. iPS cells can be generated by introduction of transcription factors, such as OCT4, SOX2, KLF4, and CMYC. iPS cells resemble embryonic stem cells in their properties and differentiation potential. The mechanisms that lead to induced pluripotency and the effect of each transcription factor are not completely understood. We performed a critical evaluation of the effect of overexpressing OCT4 in mesenchymal stem cells and fibroblasts and found that OCT4 can activate the expression of other stemness genes, such as SOX2, NANOG, CMYC, FOXD3, KLF4, and ßCATENIN, which are not normally or are very weakly expressed in mesenchymal stem cells. Transient expression of OCT4 was also performed to evaluate whether these genes are affected by its overexpression in the first 48 h. Transfected fibroblast cells expressed around 275-fold more OCT4 than non-transfected cells. In transient expression, in which cells were analyzed after 48 h, we detected only the up-regulation of FOXD3, SOX2, and KLF4 genes, suggesting that these genes are the earlier targets of OCT4 in this cellular type. We conclude that forced expression of OCT4 can alter cell status and activate the pluripotent network. Knowledge gained through study of these systems may help us to understand the kinetics and mechanism of cell reprogramming.

Lung transplantation for cystic fibrosis: outcome of 101 single-center consecutive patients.

Bilateral sequential lung transplantation (BSLT) is nowadays considered a valid therapeutic option for patients with end stage cystic fibrosis. We report our experience with 104 BSLTs in 101 patients. The overall survivals at 1, 3, 5, 10 years were 79%, 65%, 58%, and 42%, respectively. Perioperative mortality was 14.8% (n = 15). The leading causes of perioperative mortality were primary graft dysfunction and sepsis. Three patients were retransplanted owing to obliterative bronchiolitis. In 70 cases (69%), patients displayed ≥ 1 additional risk factors: previous lung resections, colonization by Burkholderia cepacia, diabetes, pneumothorax, or noninvasive ventilatory support. The mean preoperative 1-second forced expiratory volume of 0.69 ± 0.2 L (22%) increased to 85% at 1 year after the operation. The mean time on the waiting list was 12 ± 5 months. The 5 patients treated with extracorporeal membrane oxygenation before urgent transplantation were operated after 3, 5, 6, 30, and 3 days respectively. During the procedure, cardiopulmonary bypass was required in 33 patients (32%). Lung transplantation represents a unique opportunity to ameliorate the quality and improve the survival of patients affected by cystic fibrosis. Timing of referral and patient selection remain crucial for success.

Interferon-γ inhibits integrin-mediated extracellular signal-regulated kinase activation stimulated by fibronectin binding in thyroid cells.

Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by the presence of specific antibodies and by a lymphocytic infiltration of the thyroid secreting inflammatory cytokines. Macrophages, lymphocytes, and cytokines play a pivotal role in both development and progression of Th1-mediated autoimmune diseases, and a direct role in the destruction of thyroid follicles and follicular cell function in autoimmune thyroiditis. Integrins are integral membrane receptors involved in cell-extra-cellular matrix (ECM) interaction with both structural and signaling functions. The integrin- ECM interaction is necessary for the correct function and survival of thyroid follicular cells. The purpose of this study was to determine the effect of cytokine stimulation on integrin expression and signaling in the thyroid cell. Primary cultures from normal thyroids were treated with interferon-γ (IFN-γ), INF-α, tumor necrosis factor-α, interleukin 1a or these cytokines all together. Integrin expression, cell adhesion to fibronectin (FN) and FN-stimulated extracellular signal-regulated kinase (ERK) phosphorylation were determined after cytokine treatment. IFN-γ and IFN-α were the most effective, reducing the expression of the integrin αvß3 and slightly increasing the α3ß1. Cell treatment with IFN-γ strongly impaired cell adhesion to FN. At the same time, the treatment with IFN-γ dramatically inhibited the stimulation of ERK phosphorylation induced by cell adhesion to FN. In conclusion, IFN-γ inhibits the expression of the integrin αvß3, reducing the cell adhesion to FN and the following intracellular signaling in thyroid cells in culture. These results suggest that integrins may be a target of the infiltrating lymphocytes and have a role in the pathogenesis of autoimmune thyroiditis.