Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorders (SMPLPD), demographical, clinical, therapeutic and prognostic aspects: a retrospective monocentric analysis.

Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorders (SMPLPD), also known as PCS-TCLPD, represent a rare group of hematologic diseases primarily affecting the skin. In this retrospective single-centre case series study, we aimed to investigate the demographic, clinical, therapeutic, and prognostic aspects of SMPLPD. We collected data from cases diagnosed between 2010 and the present, employing histopathological and immunohistochemical methods following WHO criteria. We included 22 patients with a median age of 61.50 years and median time between clinical onset and diagnosis of 3.00 months. Surgical excision with conservative margins was the primary choice, showing clinical remission in 17 cases, while non-surgical treatments, including radiotherapy, high-potency steroid treatment and ablative laser, achieved clinical remission in four cases. Clinical presentations varied, but the most common one was a single violaceous nodule/papule on upper body parts. In conclusion, our single-centre case series provides valuable insights into SMPLPD, highlighting the effectiveness of surgical treatments and the potential of non-surgical ones. Even if controversial, the benign nature of SMPLPD emphasizes the importance of achieving tumour clearance with acceptable aesthetic outcomes.

Offloading systems for the treatment of neuropathic foot ulcers in patients with diabetes mellitus: a meta-analysis of randomized controlled trials for the development of the Italian guidelines for the treatment of diabetic foot syndrome.

AIM: To compare the effectiveness of commonly used offloading devices for the treatment of neuropathic foot ulcers in patients with diabetes mellitus. This meta-analysis (MA) has been performed for giving an answer to clinical questions on this topic of the Italian guideline on diabetic foot syndrome. METHODS: The present MA includes randomized controlled studies (duration > 12 weeks) comparing, in patients with diabetes mellitus and non-infected neuropathic foot ulcer: any offloading device vs either no offloading device or conventional footwear; removable versus non-removable offloading devices; surgical procedure vs other offloading approaches. The primary endpoint was ulcer healing. RESULTS: A total of 184 studies were identified, and 18 were considered eligible for the analysis. We found that: any plantar off-loading, when compared to the absence of plantar offloading device, is associated with a higher ulcer healing (MH-OR: 3.13 [1.08, 9.11], p = 0.04, I2 = 0%); total contact cast or nonremovable knee-high walker, compared to other offloading devices, had a higher ulcer healing rate (MH-OR: 2.64 [1.43, 4.89], p = 0.002, I2 = 51%); surgical offloading for active ulcers in combination with post-surgery offloading achieves higher ulcer healing rate when compared to offloading devices alone (MH-OR: 6.77 [1.64, 27.93], p = 0.008, I2 = 0%). CONCLUSIONS: Any plantar offloading, compared to the absence of plantar offloading device, is associated with a higher ulcer healing rate. Total contact cast or nonremovable knee-high walker, compared to other offloading devices, is preferable. Surgical offloading for active ulcers, in combination with post-surgery offloading devices, achieves a higher ulcer healing rate when compared to other offloading devices alone. Further studies with a larger cohort of patients with diabetic neuropathic foot ulcers and extended follow-up periods are necessary.

A multi-national survey to identify clinicians' perspectives concerning Proton Pump inhibitors in patients with systemic sclerosis.

OBJECTIVES: Proton Pump Inhibitors (PPIs) are widely used in SSc for gastroesophageal reflux disease (GERD). However, there is little evidence to support their empirical use and long-term safety has been questioned. Our objective was to better describe clinicians' attitudes toward PPIs prescription and use in SSc patients. METHODS: Clinicians involved in the care of SSc patients were invited through international physician networks and social media to participate in an online survey. RESULTS: Responses from 227 clinicians from 36 countries were evaluable. The majority 'agreed' (41.4 %) or 'strongly agreed' (45.4 %) that GERD is a major cause of morbidity in SSc. Lifestyle modifications are seldom (16 %) considered effective. Only half 'agreed' (43 %) or 'strongly agreed' (11 %) there is solid evidence supporting PPIs efficacy in SSc. The most common reasons for PPIs prescription were symptomatic GERD unresponsive to lifestyle modification (95 %), objective evidence of GERD (82 %), and hoarseness or respiratory symptoms (71 %). There are variable concerns about PPIs long-term safety in SSc. The three highest (mean) reasons (0-10, here 10 is 'very concerned') were: small intestinal bacterial overgrowth (5.5), osteoporosis (5.4), and drug interactions (5.2). There are significant differences in attitudes towards surgery for refractory GERD, and concerns about potential complications. PPIs may have a putative role for disease modification (e.g., ILD and calcinosis), and the role of immunosuppression is uncertain for GI (gastrointestinal) disease in SSc. CONCLUSION: PPIs are frequently prescribed in SSc. Side effects are a recognized concern, especially regarding long-term therapy. There is significant variation in attitudes towards surgical intervention. Future research and practical treatment recommendation for PPIs in SSc are urgently needed.

Nailfold Capillaroscopy Analysis Can Add a New Perspective to Biomarker Research in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), all of which are characterised by inflammation of small-medium-sized vessels. Progressive understanding of these diseases has allowed researchers and clinicians to start discussing nailfold video capillaroscopy (NVC) as a future tool for many applications in daily practice. Today, NVC plays a well-established and validated role in differentiating primary from secondary Raynaud's phenomenon correlated with scleroderma. Nevertheless, there has not been sufficient attention paid to its real potential in the ANCA-associated vasculitis. In fact, the role of NVC in vasculitis has never been defined and studied in a multicentre and multinational study. In this review, we carried out a literature analysis to identify and synthesise the possible role of capillaroscopy for patients with ANCA-associated vasculitis. METHODS: Critical research was performed in the electronic archive (PUBMED, UpToDate, Google Scholar, ResearchGate), supplemented with manual research. We searched in these databases for articles published until November 2023. The following search words were searched in the databases in all possible combinations: capillaroscopy, video capillaroscopy, nailfold-video capillaroscopy, ANCA-associated vasculitis, vasculitis, granulomatosis with polyangiitis, EGPA, and microscopic polyangiitis. RESULTS: The search identified 102 unique search results. After the evaluation, eight articles were selected for further study. The literature reported that capillaroscopy investigations documented non-specific abnormalities in 70-80% of AAV patients. Several patients showed neoangiogenesis, capillary loss, microhaemorrhages, and bushy and enlarged capillaries as the most frequent findings. Furthermore, the difference between active phase and non-active phase in AAV patients was clearly discernible. The non-active phase showed similar rates of capillaroscopy alterations compared to the healthy subjects, but the active phase had higher rates in almost all common abnormalities instead. CONCLUSIONS: Microvascular nailfold changes, observed in patients affected by vasculitis, may correlate with the outcome of these patients. However, these non-specific abnormalities may help in the diagnosis of vasculitis. As such, new analysis analyses are necessary to confirm our results.

A Multinational Survey Investigating the Unmet Needs and Patient Perspectives Concerning Proton Pump Inhibitors in Systemic Sclerosis.

OBJECTIVE: Proton pump inhibitors (PPIs) are widely prescribed to treat gastroesophageal reflux disease (GERD) in Systemic Sclerosis (SSc). However, not all patients adequately respond to the treatment, and there are frequent concerns about the safety of long-term use of PPIs. Our aim was to identify the main problems/complaints of SSc patients on PPIs, as well as understand their unmet needs. METHODS: SSc patients treated with PPIs were invited through international patient associations and social media to participate in an online survey. RESULTS: We gathered 301 valid responses from 14 countries (United Kingdom 19.3% and United States 70.4%). Multiple PPIs use (two: 30% and three: 21% in series) was common. The majority (89%) reported improvement in gastrointestinal symptoms from receiving PPIs. Side effects attributed to receiving PPIs were uncommon (19%); however, most (79%) were potentially concerned. Around half (58%) had received lifestyle information, and most (85%) had searched online for information about PPIs. Only in the minority (12%) had a surgical approach been discussed; however, half (46%) indicated that they would be willing to undergo surgery to resolve their GERD symptoms but had important concerns. CONCLUSION: Despite the frequent use of PPIs in patients with SSc, there is significant heterogeneity in prescription, and combination therapy (PPIs plus other medication for acid reflux) is not uncommon (approximately 40%). Patients have significant concerns about PPIs side effects. Education about PPIs is often neglected, and patients very frequently use online sources to obtain information on drug treatment. A surgical approach is infrequently discussed, and patients fear this potential therapeutic approach.

Bariatric Surgery for Patients with Overweight/Obesity. A Comprehensive Grading Methodology and Network Metanalysis of Randomized Controlled Trials on Weight Loss Outcomes and Adverse Events.

This study aims to compare different types of metabolic bariatric surgery (MBS) with lifestyle intervention/medical therapy (LSI/MT) for the treatment of overweight/obesity. The present and network meta-analysis (NMA) includes randomized trials. MBS was associated with a reduction of BMI, body weight, and percent weight loss, when compared to LSI/MT, and also with a significant reduction of HbA1c and a higher remission of diabetes. Meta-regression analyses revealed that BMI, a higher proportion of women, and a longer duration of trial were associated with greater effects of MBS. The NMA showed that all surgical procedures included (except greater curvature plication) were associated with a reduction of BMI. MBS is an effective option for the treatment of obesity. The choice of BMI thresholds for eligibility for surgery of patients with different complications should be performed making an evaluation of risks and benefits in each BMI category.

Visceral larva Migrans in a Young Italian Patient: A Diagnostic Dilemma.

BACKGROUND: The association of fever, focal hepatic lesions and peripheral hyper-eosinophilia (FHLH) can be observed in both infectious and non-infectious conditions. Fascioliasis, capillariasis, toxocariasis, all causes of visceral larva migrans (VLM), represent most of the former, whilst lymphomas, eosinophilic leukemias and mastocytosis belong in the non-infectious conditions. METHODS: We prospectively followed a young patient presenting with FHLH in the Tuscany region of Italy. RESULTS: The patient was subject to serological and parasitological examination in an attempt to clarify the origin of the lesions. Serologies for both Fasciola hepatica and Toxocara spp. were positive, with the latter presenting a higher index. We opted for treatment with a prolonged course of albendazole due to the serological results and being toxocariasis more frequent in our setting. The patient was then subject to radiological follow-up. The patient responded to treatment with albendazole as shown by a decrease in eosinophils, seronegativization for Toxocara spp., clinical and radiological improvement. Toxocariasis was hence considered the most likely diagnosis. CONCLUSIONS: Parasitic infections cannot be disregarded in the presence of FHLH. Differential diagnosis between these parasitic infections can be challenging due to the presence of similar clinical presentations and serological cross-reactions, and follow-up of the patient is needed to ensure optimal treatment outcomes.

Metabolic bariatric surgery as a therapeutic option for patients with type 2 diabetes: A meta-analysis and network meta-analysis of randomized controlled trials.

AIM: To compare different types of metabolic surgery with non-surgical therapy for the treatment of type 2 diabetes (T2D). METHODS: The present network meta-analysis (NMA) includes randomized clinical trials (duration ≥ 52 weeks) comparing different surgery techniques with non-surgical therapy in diabetes patients. The primary endpoints were endpoint HbA1c, body mass index (BMI) and diabetes remission. The secondary endpoints included fasting plasma glucose, lipid profile, blood pressure, arterial hypertension and dyslipidaemia remission, quality of life and surgical adverse events. Indirect comparisons of different types of surgery were performed by NMA. Mean and 95% confidence intervals for continuous variables, and the Mantel-Haenzel odds ratio for categorial variables, were calculated. RESULTS: The types of surgical procedure included laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), bilio-pancreatic diversion (BPD), greater curvature plication (GCP), one-anastomosis gastric bypass (OAGB) and Duodeno-Jejunal bypass. Thirty-six trials were included. Metabolic bariatric surgery (MBS) was associated with a significantly higher reduction of HbA1c, diabetes remission and BMI compared with medical therapy. In the NMA, a significant reduction of HbA1c was observed with OAGB and SG. Complete diabetes remission significantly increased with all surgical procedures in comparison with non-surgical therapy, except for GCP. In addition, only BPD, RYGB and OAGB were associated with a significant reduction of BMI. CONCLUSIONS: MBS is an effective option for the treatment of T2D in patients with obesity. Further long-term trials of appropriate quality are needed for assessing the risk-benefit ratio in some patient cohorts, such as those with a BMI of less than 35 kg/m2 and aged older than 65 years.

Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort).

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Transthyretin Cardiac Amyloidosis: A Cardio-Orthopedic Disease.

Orthopaedic manifestations of wild-type transthyretin amyloidosis are frequent and characteristic, including idiopathic bilateral carpal tunnel syndrome, idiopathic lumbar canal stenosis, atraumatic rupture of the brachial biceps tendon, and, more rarely, finger disease and rotator cuff. These manifestations often coexisting in the same patient, frequently male and aged, steadily precede cardiac involvement inducing a rapidly progressive heart failure with preserved ejection fraction. Although transthyretin cardiac amyloidosis remains a cardiac relevant disease, these extracardiac localisation may increase diagnostic suspicion and allow for early diagnosis assuming the role of useful diagnostic red flags, especially in light of new therapeutic opportunities that can slow or stop the progression of the disease. For the cardiologist, the recognition of these extracardiac red flags is of considerable importance to reinforce an otherwise less emerging diagnostic suspicion. For orthopedists and rheumatologists, the presence in an old patient with or without clinical manifestations of cardiovascular disease, of an unexpected and inexplicable constellation of musculoskeletal symptoms, can represent a fundamental moment for an early diagnosis and treatment is improving a patient's outcome.

Development of the Italian Clinical Practice Guidelines on Bariatric and Metabolic Surgery: Design and Methodological Aspects.

Development of the Italian clinical practice guidelines on bariatric and metabolic surgery, as well as design and methodological aspects. BACKGROUND: Obesity and its complications are a growing problem in many countries. Italian Society of Bariatric and Metabolic Surgery for Obesity (Società Italiana di Chirurgia dell'Obesità e delle Malattie Metaboliche-SICOB) developed the first Italian guidelines for the treatment of obesity. METHODS: The creation of SICOB Guidelines is based on an extended work made by a panel of 24 members and a coordinator. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology has been used to decide the aims, reference population, and target health professionals. Clinical questions have been created using the PICO (Patient, Intervention, Comparison, Outcome) conceptual framework. The definition of questions used the two-step web-based Delphi method, made by repeated rounds of questionnaires and a consensus opinion from the panel. RESULTS: The panel proposed 37 questions. A consensus was immediately reached for 33 (89.2%), with 31 approved, two rejected and three which did not reach an immediate consensus. The further discussion allowed a consensus with one approved and two rejected. CONCLUSIONS: The areas covered by the clinical questions included indications of metabolic/bariatric surgery, types of surgery, and surgical management. The choice of a surgical or a non-surgical approach has been debated for the determination of the therapeutic strategy and the correct indications.

Severe neurologic impairment and respiratory failure after fall and hip fracture in an elderly woman.

Fat embolism syndrome is a rare complication of long bone fractures and orthopedic surgery. We report a case of a 90-year-old woman who developed severe neurologic impairment and respiratory failure few hours after an accidental fall complicated by fracture of the left femur neck and left humerus.

Dural Metastasis without Subdural Hematoma or Subdural Fluid Collection in a Patient with Signet Ring Cell Gastric Adenocarcinoma.

BACKGROUND Signet ring cell (SRC) gastric adenocarcinoma is an aggressive histotype associated with poor prognosis, especially in advanced gastric cancer. Dural metastasis is rarely described in the literature, and clinical manifestations are generally related to subdural hematoma. Here we present a case of advanced SRC gastric cancer with dural neoplastic involvement in the absence of subdural hematoma or subdural fluid collection. CASE REPORT A 39-year-old woman presented with multiple episodes of confusion and headache. She had a history of SRC gastric adenocarcinoma that had been treated with neoadjuvant chemotherapy and total gastrectomy without evidence of disease relapse at follow-up. During hospitalization, she experienced persistent drowsiness and frequent generalized seizures that were nonresponsive to antiepileptic drugs. Brain computed tomography showed a dural right parafalcine nodular lesion suggestive of metastasis, and an SRC presence was detected in a cerebrospinal fluid sample. Cerebral magnetic resonance imaging showed isolated diffuse dural neoplastic involvement without evidence of subdural hematoma or subdural fluid collection. We considered palliative treatment with intrathecal chemotherapy, but it was not carried out because of clinical worsening and subsequent death. CONCLUSIONS In the very few case reports in the literature, dural metastasis in advanced gastric cancer is mainly associated with subdural hematoma. In our case, the absence of any subdural effusion, which is an even rarer condition, along with an unusual clinical presentation dominated by generalized seizures represented a diagnostic challenge. Given the aggressive course of the disease, a rapid diagnosis could allow a faster specific treatment to relieve a patient's symptoms.

Protein O- and C-Glycosylation pathways in Toxoplasma gondii and Plasmodium falciparum.

Apicomplexan parasites are amongst the most prevalent and morbidity-causing pathogens worldwide. They are responsible for severe diseases in humans and livestock and are thus of great public health and economic importance. Until the sequencing of apicomplexan genomes at the beginning of this century, the occurrence of N- and O-glycoproteins in these parasites was much debated. The synthesis of rudimentary and divergent N-glycans due to lineage-specific gene loss is now well established and has been recently reviewed. Here, we will focus on recent studies that clarified classical O-glycosylation pathways and described new nucleocytosolic glycosylations in Toxoplasma gondii, the causative agents of toxoplasmosis. We will also review the glycosylation of proteins containing thrombospondin type 1 repeats by O-fucosylation and C-mannosylation, newly discovered in Toxoplasma and the malaria parasite Plasmodium falciparum. The functional significance of these post-translational modifications has only started to emerge, but the evidence points towards roles for these protein glycosylation pathways in tissue cyst wall rigidity and persistence in the host, oxygen sensing, and stability of proteins involved in host invasion.

A rare case of Candida glabrata spondylodiscitis: case report and literature review.

BACKGROUND: Spondylodiscitis is an infection of the vertebral column, the incidence of which is increasing due to an increase in the susceptible population and improved ascertainment. This disease has been associated with a wide range of microorganisms. Fungal spondylodiscitis is uncommon (0.5-1.6%) and strongly associated with immunosuppression and diabetes (Gouliouris et al., 2010). A rare case of Candida glabrata spondylodiscitis in a non-neutropenic diabetic patient is reported herein, along with a review of the literature. CASE REPORT: A case of C. glabrata spondylodiscitis of L3-L4 metameres was diagnosed. The diagnosis was obtained through open biopsy of an abscess and culture examination. The patient was treated with anidulafungin and surgical debridement of the lesion. CONCLUSIONS: The diagnosis of spondylodiscitis is often delayed or missed. Physicians should consider this entity in the differential diagnosis of lumbar pain in order to initiate an appropriate therapy to prevent spinal cord lesions and disability. This is particularly relevant in the case of a fungal aetiology, as there is a recognized global shift towards invasive candidiasis due to non-albicans Candida species, in particular C. glabrata, which has variable susceptibility to antifungal drugs.

Ethanol and isopropanol in concentrations present in hand sanitizers sharply reduce excystation of Giardia and Entamoeba and eliminate oral infectivity of Giardia cysts in gerbils.

Enteric protozoan parasites, which are spread by the fecal-oral route, are important causes of diarrhea (Giardia duodenalis) and amebic dysentery (Entamoeba histolytica). Cyst walls of Giardia and Entamoeba have a single layer composed of fibrils of ß-1,3-linked GalNAc and ß-1,4-linked GlcNAc (chitin), respectively. The goal here was to determine whether hand sanitizers that contain ethanol or isopropanol as the active microbicide might reduce transmission of these parasites. We found that treatment with these alcohols with or without drying in a rotary evaporator (to model rapid evaporation of sanitizers on hands) kills 85 to 100% of cysts of G. duodenalis and 90 to 100% of cysts of Entamoeba invadens (a nonpathogenic model for E. histolytica), as shown by nuclear labeling with propidium iodide and failure to excyst in vitro. Alcohols with or without drying collapsed the cyst walls of Giardia but did not collapse the cyst walls of Entamoeba. To validate the in vitro results, we showed that treatment with alcohols eliminated oral infection of gerbils by 1,000 G. duodenalis cysts, while a commercial hand sanitizer (Purell) killed E. invadens cysts that were directly applied to the hands. These results suggest that expanded use of alcohol-based hand sanitizers might reduce the transmission of Giardia and Entamoeba.