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Article: Sodium Glucose Cotransporter-2 Inhibitors in Non-Diabetic Kidney Disease: Evidence in Experimental Models.

Castoldi, Giovanna / Carletti, Raffaella / Barzaghi, Francesca / Meani, Michela / Zatti, Giovanni / Perseghin, Gianluca / Di Gioia, Cira R T / Zerbini, Gianpaolo

Pharmaceuticals (Basel, Switzerland)

2024 Volume 17, Issue 3

Abstract: Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering agents widely used for the treatment of type 2 diabetes mellitus. A number of clinical trials in type 2 diabetic patients with different degrees of renal impairment have ... ...

Abstract	Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering agents widely used for the treatment of type 2 diabetes mellitus. A number of clinical trials in type 2 diabetic patients with different degrees of renal impairment have clearly demonstrated that SGLT2 inhibitors reduce the progression rate of diabetic kidney disease. Furthermore, recent studies have shown that SGLT2 inhibitors also exert a protective effect in the case of non-diabetic kidney disease. Consequently, it has been hypothesized that the nephroprotective activity of these drugs could exceed the canonical impact on glycemic control and that the resulting beneficial effects could be the consequence of their pleiotropic properties (proven reduction of inflammation, fibrosis, oxidative stress and sympathetic nervous activity) both at systemic and tissue levels, suggesting that the efficacy of these drugs could also be extended to non-diabetic nephropathies. This review focuses on the nephroprotective effects of SGLT2 inhibitors in different experimental models of non-diabetic kidney disease. The different glucose-independent mechanisms potentially implemented by SGLT2 inhibitors to ultimately protect the non-diabetic kidney are described in detail, and conflicting results, when present, are discussed.
Language	English
Publishing date	2024-03-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph17030362
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Article: Meniscal Allograft Transplants in Skeletally Immature Patients: A Systematic Review of Indications and Outcomes.

Turati, Marco / Boerci, Linda / Piatti, Massimiliano / Russo, Laura / Rigamonti, Luca / Buonanotte, Francesco / Courvoisier, Aurelien / Zatti, Giovanni / Piscitelli, Daniele / Bigoni, Marco

Healthcare (Basel, Switzerland)

2023 Volume 11, Issue 9

Abstract: Meniscal lesions in skeletally immature patients can lead to joint degradation and knee instability. Meniscal allograft transplant (MAT) surgery is a solution to maintain knee stability. There is a lack of consensus on MAT surgery outcomes in pediatric ... ...

Abstract	Meniscal lesions in skeletally immature patients can lead to joint degradation and knee instability. Meniscal allograft transplant (MAT) surgery is a solution to maintain knee stability. There is a lack of consensus on MAT surgery outcomes in pediatric patients. A systematic review was conducted according to the PRISMA guidelines. PubMed, Scopus and EMBASE databases were searched from 1965 to June 2022. Studies were evaluated using the Newcastle-Ottawa Scale (NOS). Three studies were selected, and 58 patients were included (mean age 15.9 years) in total. The lateral meniscus was involved in 82.8% of all MAT surgeries. Post-meniscectomy syndrome and discoid meniscus were the main indications for MAT surgery. All studies reported improved subjective clinical scores and levels of sport after the surgery. The complication rate was 27.5%. Partial meniscectomy, meniscus knot removal, chondral defect treatment and lysis of adhesions were the most frequent procedures performed during reoperation. MAT surgery can improve clinical outcomes in pediatric patients with strictly selected indications. MAT surgery is safe when there are no limb asymmetries or malalignments, but it remains a challenging procedure with a high complication rate. Long-term follow-up is needed for definitive statements on the use of MAT in skeletally immature patients.
Language	English
Publishing date	2023-05-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2721009-1
ISSN	2227-9032
ISSN	2227-9032
DOI	10.3390/healthcare11091312
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Article ; Online: Cardioprotective Effects of Sodium Glucose Cotransporter 2 Inhibition in Angiotensin II-Dependent Hypertension Are Mediated by the Local Reduction of Sympathetic Activity and Inflammation.

Castoldi, Giovanna / Carletti, Raffaella / Ippolito, Silvia / Colzani, Massimiliano / Pelucchi, Sara / Zerbini, Gianpaolo / Perseghin, Gianluca / Zatti, Giovanni / di Gioia, Cira R T

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: The cardioprotective effects of sodium glucose cotrasponter 2 (SGLT2) inhibitors seem to be independent from the effects on glycemic control, through little-known mechanisms. In this study, we investigate whether the cardioprotective effects of ... ...

Abstract	The cardioprotective effects of sodium glucose cotrasponter 2 (SGLT2) inhibitors seem to be independent from the effects on glycemic control, through little-known mechanisms. In this study, we investigate whether the cardioprotective effects of empagliflozin, a SGLT2 inhibitor, may be associated with myocardial sympathetic activity and inflammatory cell infiltration in an experimental model of angiotensin II-dependent hypertension. Angiotensin II (Ang II), Ang II plus Empagliflozin, physiological saline, or physiological saline plus empagliflozin were administered to Sprague Dawley rats for two weeks. Blood pressure was measured by plethysmographic method. Myocardial hypertrophy and fibrosis were analysed by histomorphometry, and inflammatory cell infiltration and tyrosine hydroxylase expression, implemented as a marker of sympathetic activity, were evaluated by immunohistochemistry. Ang II increased blood pressure, myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase expression, as compared to the control group. Empagliflozin administration prevented the development of myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase overexpression in Ang II-treated rats, without affecting blood glucose and the Ang II-dependent increase in blood pressure. These data demonstrate that the cardioprotective effects of SGLT2 inhibition in Ang II-dependent hypertension may result from the myocardial reduction of sympathetic activity and inflammation and are independent of the modulation of blood pressure and blood glucose levels.
MeSH term(s)	Rats ; Animals ; Angiotensin II/metabolism ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; Rats, Sprague-Dawley ; Sodium-Glucose Transporter 2 ; Blood Glucose ; Tyrosine 3-Monooxygenase/metabolism ; Hypertension/drug therapy ; Hypertension/metabolism ; Cardiomegaly ; Blood Pressure ; Inflammation/drug therapy ; Fibrosis
Chemical Substances	Angiotensin II (11128-99-7) ; empagliflozin (HDC1R2M35U) ; Sodium-Glucose Transporter 2 Inhibitors ; Sodium-Glucose Transporter 2 ; Blood Glucose ; Tyrosine 3-Monooxygenase (EC 1.14.16.2)
Language	English
Publishing date	2023-06-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241310710
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Article ; Online: Clinical outcomes and complications of S53P4 bioactive glass in chronic osteomyelitis and septic non-unions: a retrospective single-center study.

Gatti, Simone Daniel / Gaddi, Diego / Turati, Marco / Leone, Giulio / Arts, Jacobus J / Pessina, Fabio / Carminati, Mattia / Zatti, Giovanni / De Rosa, Laura / Bigoni, Marco

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology

2024 Volume 43, Issue 3, Page(s) 489–499

Abstract: Introduction: Dead space management following debridement surgery in chronic osteomyelitis or septic non-unions is one of the most crucial and discussed steps for the success of the surgical treatment of these conditions. In this retrospective clinical ... ...

Abstract	Introduction: Dead space management following debridement surgery in chronic osteomyelitis or septic non-unions is one of the most crucial and discussed steps for the success of the surgical treatment of these conditions. In this retrospective clinical study, we described the efficacy and safety profile of surgical debridement and local application of S53P4 bioactive glass (S53P4 BAG) in the treatment of bone infections. Methods: A consecutive single-center series of 38 patients with chronic osteomyelitis (24) and septic non-unions (14), treated with bioactive glass S53P4 as dead space management following surgical debridement between May 2015 and November 2020, were identified and evaluated retrospectively. Results: Infection eradication was reached in 22 out of 24 patients (91.7%) with chronic osteomyelitis. Eleven out of 14 patients (78.6%) with septic non-union achieved both fracture healing and infection healing in 9.1 ± 4.9 months. Three patients (7.9%) developed prolonged serous discharge with wound dehiscence but healed within 2 months with no further surgical intervention. Average patient follow-up time was 19.8 months ± 7.6 months. Conclusion: S53P4 bioactive glass is an effective and safe therapeutic option in the treatment of chronic osteomyelitis and septic non-unions because of its unique antibacterial properties, but also for its ability to generate a growth response in the remaining healthy bone at the bone-glass interface.
MeSH term(s)	Humans ; Retrospective Studies ; Bone Substitutes/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Persistent Infection ; Osteomyelitis/drug therapy ; Osteomyelitis/surgery ; Osteomyelitis/microbiology
Chemical Substances	Bone Substitutes ; Anti-Bacterial Agents
Language	English
Publishing date	2024-01-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	603155-9
ISSN	1435-4373 ; 0934-9723 ; 0722-2211
ISSN (online)	1435-4373
ISSN	0934-9723 ; 0722-2211
DOI	10.1007/s10096-023-04737-z
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Article: Non-Union Scoring System (NUSS): Is It Enough in Clinical Practice?

Gaddi, Diego / Gatti, Simone D / Piatti, Massimiliano / Poli, Andrea / De Rosa, Laura / Riganti, Andrea / Zatti, Giovanni / Bigoni, Marco / Turati, Marco

Indian journal of orthopaedics

2022 Volume 57, Issue 1, Page(s) 137–145

Abstract: Introduction: Bone consolidation defects represent a real orthopedic challenge because of the absence of validated treatment guidelines that can assist the surgeon in his choices. The aim of this study is to evaluate the appropriateness of the Non-Union ...

Abstract	Introduction: Bone consolidation defects represent a real orthopedic challenge because of the absence of validated treatment guidelines that can assist the surgeon in his choices. The aim of this study is to evaluate the appropriateness of the Non-Union Scoring System NUSS treatment protocol in the management of long bone non-unions by comparing it to the experience-based therapeutic approach carried out in our facility. Materials and methods: We conducted a comparative outcome study of a retrospective series of 89 patients surgically treated for long bone non-union in our facility vs. clinical results reported by Calori et al. obtained following the NUSS treatment protocol. Results: Radiographic healing was reached in 13/13 non-unions (100%) in group NUSS 1, in 58/62 (93.5%) in group NUSS 2, and in 13/14 (92.9%) in group NUSS 3. The mean time to radiographic healing was 5.69 ± 2.09 months in group 1, 7.38 ± 3.81 months in group 2 and 9.23 ± 2.31 months in group 3. 91% of patients in group I, 69% in group II and 48% in group III received what would be considered by the NUSS treatment protocol an "overtreatment", especially from a biological stand point. The comparative outcome analysis shows that our case series achieved significantly higher global healing rates ( Conclusion: From the results obtained, we can assume that the NUSS treatment protocol might underestimate the necessary therapies, particularly from a biological point of view.
Language	English
Publishing date	2022-12-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	603194-8
ISSN	0019-5413
ISSN	0019-5413
DOI	10.1007/s43465-022-00767-5
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Zs.A 1720: Show issues

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Article ; Online: Johann Peter Frank (1745-1821) and the Pathogenesis of Back Pain.

Riva, Michele Augusto / Anghilieri, Filippo Maria / Belingheri, Michael / Zatti, Giovanni

Spine

2019 Volume 44, Issue 19, Page(s) E1159–E1160

Abstract: Johann Peter Frank (1745-1821) is generally known as one of the founders of the modern Hygiene and Public Health. It is less known his contribution in investigating the pathogenesis of spinal disorders. In his "De Vertebralis Columnae in Morbis ... ...

Abstract	: Johann Peter Frank (1745-1821) is generally known as one of the founders of the modern Hygiene and Public Health. It is less known his contribution in investigating the pathogenesis of spinal disorders. In his "De Vertebralis Columnae in Morbis Dignitate" (1791), Frank first proposed to use the Latin term "rhachialgia" (back pain) to indicate all the painful states of spine. He focused on the "plethora spinali" in the vessels of the spinal cord and its membrane, sustaining that blood congestion was the origin of all the spinal disorders. He also believed that the excess of blood was able to generate a "diffuse inflammation" of vertebral and medullary structures. The innovative concepts developed by Johann Peter Frank demonstrated that he could be worthily considered as a pioneer in the study of spinal disorders.Level of Evidence: 5.
MeSH term(s)	Back Pain/etiology ; Back Pain/history ; Back Pain/pathology ; Back Pain/physiopathology ; Germany ; History, 18th Century ; History, 19th Century ; Humans ; Physicians/history ; Public Health/history ; Spinal Diseases/etiology ; Spinal Diseases/history ; Spinal Diseases/pathology ; Spinal Diseases/physiopathology
Language	English
Publishing date	2019-09-12
Publishing country	United States
Document type	Historical Article ; Journal Article
ZDB-ID	752024-4
ISSN	1528-1159 ; 0362-2436
ISSN (online)	1528-1159
ISSN	0362-2436
DOI	10.1097/BRS.0000000000003074
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Article ; Online: Updates on etiopathogenesis of musculoskeletal injuries in adolescent athletes.

Turati, Marco / Boerci, Linda / Piatti, Massimiliano / Zanchi, Nicolò / Zatti, Giovanni / Accadbled, Franck / Bigoni, Marco

Minerva pediatrics

2020 Volume 75, Issue 1, Page(s) 133–135

MeSH term(s)	Humans ; Adolescent ; Musculoskeletal Diseases ; Athletes
Language	English
Publishing date	2020-10-27
Publishing country	Italy
Document type	Journal Article
ZDB-ID	3062664-X
ISSN	2724-5780
ISSN (online)	2724-5780
DOI	10.23736/S2724-5276.20.05944-7
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Article ; Online: Femoral revision in periprosthetic fractures using a titanium modular fluted tapered stem: mortality and clinical and radiological outcomes.

Munegato, Daniele / Caminita, Agostino Dario / Sotiri, Romeo / Rossi, Andrea / Bigoni, Marco / Zatti, Giovanni

Hip international : the journal of clinical and experimental research on hip pathology and therapy

2020 Volume 30, Issue 2_suppl, Page(s) 101–107

Abstract: Introduction: The aim of the study was to evaluate the mortality and the outcomes of femoral revision in periprosthetic femoral fractures (PFF) using a titanium modular fluted tapered stem.: Methods: We retrospectively reviewed femoral revisions ... ...

Abstract	Introduction: The aim of the study was to evaluate the mortality and the outcomes of femoral revision in periprosthetic femoral fractures (PFF) using a titanium modular fluted tapered stem. Methods: We retrospectively reviewed femoral revisions performed for PFF with a titanium modular fluted tapered stem in 25 patients. The average age was 74.32 years. In 21 patients the type of fracture was Vancouver B2 and type B3 in 4 cases. The mean follow-up was 29.16 (0.83-104.1) months SD ± 29.49. Results: The 30-day and 1-year mortality were 8% and 12% respectively. The mean value of the Charlson Comorbidity Index was 4.8 and the mean value of ASA score was 2.4. The average time to surgery from admittance was 5.45 days with 20% of patients operated on within 48 hours. A significant correlation was found between ASA score and mortality. The mean HHS was 76 points; good-excellent results were recorded in 56% of patients. 72% had no pain and 28% had slight pain (VAS 1-3). 52% of patients were able to walk without pain, limp or aids. The mean implant subsidence was 1.57 mm and superior to 5 mm in 2 cases. As complications we recorded 4 implant dislocations (16%) and 2 infections. Reoperation rate was 12%. Conclusions: Femoral revision with a modular fluted tapered stem in patients with periprosthetic fractures results in good clinical and radiological outcomes. However, mortality remains high and, despite the modularity design, dislocation is the most frequent complication.
MeSH term(s)	Aged ; Arthroplasty, Replacement, Hip/adverse effects ; Femoral Fractures/diagnostic imaging ; Femoral Fractures/surgery ; Hip Prosthesis/adverse effects ; Humans ; Periprosthetic Fractures/diagnostic imaging ; Periprosthetic Fractures/surgery ; Prosthesis Design ; Reoperation ; Retrospective Studies ; Titanium ; Treatment Outcome
Chemical Substances	Titanium (D1JT611TNE)
Language	English
Publishing date	2020-12-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1162513-2
ISSN	1724-6067 ; 1120-7000
ISSN (online)	1724-6067
ISSN	1120-7000
DOI	10.1177/1120700020971313
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Article: Prokineticin 2 and Cytokine Content in the Synovial Fluid of Knee Osteoarthritis and Traumatic Meniscal Tear Patients: Preliminary Results.

Turati, Marco / Franchi, Silvia / Crippa, Marco / Rizzi, Laura / Rigamonti, Luca / Sacerdote, Paola / Gatti, Simone Daniel / Piatti, Massimiliano / Galimberti, Giulia / Munegato, Daniele / Amodeo, Giada / Omeljaniuk, Robert J / Zatti, Giovanni / Torsello, Antonio / Bigoni, Marco

Journal of clinical medicine

2023 Volume 12, Issue 13

Abstract: Knee osteoarthritis (OA) is a chronic degenerative inflammatory-based condition caused by a cascade of different intra-articular molecules including several cytokines. Among the cytokines, prokineticins (PKs) have recently been identified as important ... ...

Abstract	Knee osteoarthritis (OA) is a chronic degenerative inflammatory-based condition caused by a cascade of different intra-articular molecules including several cytokines. Among the cytokines, prokineticins (PKs) have recently been identified as important mediators of inflammation and pain. This observational study examined the potential involvement of PK2 in degenerative or traumatic knee disease. Fifteen patients presenting knee osteoarthritis (OA group) and 15 patients presenting a traumatic meniscal tear (TM group) were studied. Synovial fluid samples from affected knees were assessed for PK2, IL-10, and TNF-α using the ELISA method. At a long-term follow-up (minimum 5 years, mean = 6.1 years), patients in the TM group underwent clinical re-evaluation with PROMs (Tegner Activity Scale, IKDC, Lysholm, SKV); in addition, X-ray visualization was used to assess the presence of secondary OA. PK2 was detected in synovial fluids of both TM and OA patients and the levels were comparable between the two groups, while IL-10 levels were significantly greater in the OA group than those in TM patients. PK2 levels correlated with those of IL-10. PK2 levels were greater in blood effusions compared to clear samples, did not differ significantly between sexes, nor were they related to differences in weight, height, or injury (meniscal laterality, time since dosing). No correlation was found between PROMs and radiological classifications in patients in the TM group at final follow-up. These data are the first observations of PK2 in synovial fluid following traumatic meniscus injury. These findings suggest possible further prognostic indices and therapeutic targets to limit the development of secondary OA.
Language	English
Publishing date	2023-06-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12134330
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Article ; Online: Frailty and post-operative delirium influence on functional status in patients with hip fracture: the GIOG 2.0 study.

Gandossi, Chiara Maria / Zambon, Antonella / Ferrara, Maria Cristina / Tassistro, Elena / Castoldi, Giuseppe / Colombo, Francesca / Mussi, Chiara / Martini, Emilio / Sergi, Giuseppe / Coin, Alessandra / Zatti, Giovanni / Trevisan, Caterina / Volpato, Stefano / Ungar, Andrea / Bellelli, Giuseppe

Aging clinical and experimental research

2023 Volume 35, Issue 11, Page(s) 2499–2506

Abstract: Background: This study analyzes the effect of frailty and Post-Operative Delirium (POD) on the functional status at hospital discharge and at 4-month follow-up in patients with hip fracture (HF).: Methods: Multicenter prospective observational study ... ...

Abstract	Background: This study analyzes the effect of frailty and Post-Operative Delirium (POD) on the functional status at hospital discharge and at 4-month follow-up in patients with hip fracture (HF). Methods: Multicenter prospective observational study of older patients with HF admitted to 12 Italian Orthogeriatric centers (July 2019-August 2022). POD was assessed using the 4AT. A 26-item Frailty Index (FI) was created using data collected on admission. The outcome measures were Cumulated Ambulation Score (CAS) ≤ 2 at discharge and a telephone-administered CAS ≤ 2 after 4 months. Poisson regression models were used to assess the effect of frailty and POD on outcomes. Results: 984 patients (median age 84 years, IQR = 79-89) were recruited: 480 (48.7%) were frail at admission, 311 (31.6%) developed POD, and 158 (15.6%) had both frailty and POD. In a robust Poisson regression, frailty alone (Relative Risk, RR = 1.56, 95% Confidence Intervals, CI 1.19-2.04, p = 0.001) and its combination with POD (RR = 2.57, 95% CI 2.02-3.26, p < 0.001) were associated with poor functional status at discharge. At 4-month follow-up, the combination of frailty with POD (RR 3.65, 95% CI 1.85-7.2, p < 0.001) increased the risk of poor outcome more than frailty alone (RR 2.38, 95% CI 1.21-4.66, p < 0.001). Conclusions: POD development exacerbates the negative effect that frailty exerts on functional outcomes in HF patients.
MeSH term(s)	Humans ; Aged, 80 and over ; Frailty/complications ; Emergence Delirium ; Functional Status ; Delirium ; Prospective Studies ; Hip Fractures/surgery ; Risk Factors
Language	English
Publishing date	2023-08-05
Publishing country	Germany
Document type	Observational Study ; Multicenter Study ; Journal Article
ZDB-ID	2104785-6
ISSN	1720-8319 ; 1594-0667
ISSN (online)	1720-8319
ISSN	1594-0667
DOI	10.1007/s40520-023-02522-8
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