Expression of VEGF in Peripheral Serum Is a Possible Prognostic Factor in Bone-Regeneration via Masquelet-Technique—A Pilot Study

Two-step Masquelet-technique established a new procedure in the treatment of osseous defects, addressing prerequisites postulated by the “diamond concept”. Increase in blood perfusion and growth factors are enhanced by the “Masquelet-membrane”. To describe this, we measured serum levels of Vascular Endothelial Growth Factor (VEGF) of patients with atrophic non-unions of long bones undergoing Masquelet-technique. From over 500 non-union patients undergoing Masquelet-technique with prospective follow-up we randomly selected 30 patients. 23 were included, 7 lost to follow-up or excluded because of incomplete data. Serum was drawn at specified intervals before and after surgery. Patients were followed for at least 6 months after step 2. Classification into both groups was performed according to radiological results and clinical outcome 6 months after step 2. Concentration of VEGF in patients’ serum was performed via ELISA. 14 achieved osseous consolidation (responder group), 9 cases did not (non-responder). Responders showed a significant increase of serum-VEGF in the first and second week when compared to the preoperative values of step 1. Non-responders showed a significant increase of VEGF in the second week after Steps 1 and 2. Comparison of groups showed significantly higher increase of serum-VEGF week2 after step 1 and preoperative to step 2 for responders. Results show one possibility of illustrating therapeutic progress by monitoring growth factors and possibly allowing prognostic conclusions thereof. This might lead to a more targeted treatment protocol.

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A prospective, observational clinical trial on the impact of COVID-19-related national lockdown on thyroid hormone in young males

Scientific Reports ◽

10.1038/s41598-021-86670-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Giulia Brigante ◽

Giorgia Spaggiari ◽

Barbara Rossi ◽

Antonio Granata ◽

Manuela Simoni ◽

...

Keyword(s):

Clinical Trial ◽

Serum Levels ◽

Stressful Event ◽

Italian Population ◽

Reference Ranges ◽

Endocrine Regulation ◽

Before And After ◽

Hpt Axis ◽

The Impact

AbstractTrying to manage the dramatic coronavirus disease 2019 (COVID-19) infection spread, many countries imposed national lockdown, radically changing the routinely life of humans worldwide. We hypothesized that both the pandemic per se and the consequent socio-psychological sequelae could constitute stressors for Italian population, potentially affecting the endocrine system. This study was designed to describe the effect of lockdown-related stress on the hypothalamic-pituitary-thyroid (HPT) axis in a cohort of young men. A prospective, observational clinical trial was carried out, including patients attending the male infertility outpatient clinic before and after the national lockdown for COVID-19 pandemic. The study provided a baseline visit performed before and a follow-up visit after the lockdown in 2020. During the follow-up visit, hormonal measurements, lifestyle habits and work management were recorded. Thirty-one male subjects were enrolled (mean age: 31.6 ± 6.0 years). TSH significantly decreased after lockdown (p = 0.015), whereas no significant changes were observed in the testosterone, luteinising hormone, follicle-stimulating hormone, estradiol and prolactin serum levels. No patient showed TSH serum levels above or below reference ranges, neither before nor after lockdown. Interestingly, TSH variation after lockdown was dependent on the working habit change during lockdown (p = 0.042). We described for the first time a TSH reduction after a stressful event in a prospective way, evaluating the HPT axis in the same population, before and after the national lockdown. This result reinforces the possible interconnection between psychological consequences of a stressful event and the endocrine regulation.

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Comparison of health care resource use before and after docetaxel treatment among prostate cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.215 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 215-215

Author(s):

M. Mehra ◽

Y. Wu ◽

R. Dhawan

Keyword(s):

Prostate Cancer ◽

Health Care ◽

Cancer Patients ◽

Average Length ◽

Health Care Resource ◽

Claims Database ◽

Before And After ◽

Docetaxel Treatment ◽

Lost To Follow Up

215 Background: Docetaxel is standard of care among late-stage prostate cancer patients. We analyzed patterns of health care resource utilization (RU) among patients before and after exposure to docetaxel using a large commercial claims database. Methods: A random sample of patients (N = 336) with a diagnosis of prostate cancer (ICD 9 code: 185.X) and a claim for docetaxel (2003–2009) was identified from the PharMetrics database, a nationally representative, non-payer-owned integrated commercial U.S. claims database. All patients had ≥ 12 months of enrollment prior to initiation of docetaxel. Patients were followed from their first docetaxel claim until lost to follow-up or June 30, 2009 (censored). RU was defined as all-cause hospitalization, ER, physician, and ambulatory visits. Incidence rates were derived. Results: Mean age of patients was 67.9 years (SD 10.6); mean number of docetaxel prescriptions was 9.9 (SD 10.3). Mean time to study end/lost to follow-up was 15.41 (SD 12.49) months from the index date. The table shows health care RU for the 12 months before, and over the follow-up period after docetaxel initiation. Hospitalizations, ER, physician, and ambulatory visits were significantly higher in the follow-up period. The average length of hospital stay was significantly longer after docetaxel treatment (8.2 vs 5.5 days). Prior to docetaxel, two-thirds of the patients were on hormonal therapy; 51% on analgesics, and 31% on bisphosphonates. After docetaxel, the proportions were 62%, 58%, and 54%, respectively. Conclusions: The significantly higher RU with disease progression in prostate cancer patients suggests a need for new treatment options that can effectively manage and improve patient outcomes. [Table: see text] [Table: see text]

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Optimization of Medication Regimens in Patients with Type 2 Diabetes and Clinical Atherosclerotic Cardiovascular Disease

Pharmacy ◽

10.3390/pharmacy9040186 ◽

2021 ◽

Vol 9 (4) ◽

pp. 186

Author(s):

Jarred Prudencio ◽

Paige Cajudoy ◽

Donald Waddell

Keyword(s):

Cardiovascular Disease ◽

Positive Impact ◽

Atherosclerotic Cardiovascular Disease ◽

Medication Usage ◽

Pharmacist Interventions ◽

Before And After ◽

Prescription Rates ◽

Lost To Follow Up

The American Diabetes Association recommends that patients with type II diabetes and atherosclerotic cardiovascular disease be prescribed an SGLT-2 inhibitor or GLP-1 agonist for cardioprotective benefit. This project assessed the use of these medications in this patient population in a rural clinic by measuring prescribing rates of SGLT-2/GLP-1 therapy before and after pharmacist interventions. Of the 60 patients identified at baseline, 39.39% (13/33) managed by a pharmacist were prescribed SGLT-2/GLP-1 therapy compared to the 14.81% (4/27) who had not seen a pharmacist (p = 0.025). Of the 43 patients that were not on SGLT-2/GLP-1 therapy at baseline, 13 were lost to follow-up and 13 had contraindications. For the 17 remaining patients, pharmacists recommended initiating SGLT-2/GLP-1 therapy and were able to successfully initiate therapy for 9 patients (52.94%). Pharmacist interventions improved the prescription rates from a baseline of 36.17% (17/47) to 55.3% (26/47) (p = 0.002), with SGLT-2/GLP-1 therapy contraindicated in 27.66% (13/47) of patients. This suggests that patients managed by a pharmacist have medication regimens that were optimized at a greater rate and pharmacists can have a positive impact on the appropriate medication usage in this population.

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Osteogenic Potency of Secretome Bone Marrow Derived Mesenchymal Stem Cells: A Literature Review

Advanced Science Letters ◽

10.1166/asl.2018.12684 ◽

2018 ◽

Vol 24 (8) ◽

pp. 6206-6208

Author(s):

Ismail Hadisoebroto Dilogo ◽

Jessica Fiolin ◽

Petrus Aprianto

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Factors ◽

Bone Healing ◽

Mechanical Stability ◽

Healing Process ◽

Study Groups ◽

Non Union ◽

Acute Kidney Disease ◽

Diamond Concept

Treatment of non-union bone healing has been an unsolved problem in Orthopaedic surgery despite many advances. The most commonly adapted concept is the diamond concept including the osteoprogenitor cells, osteoinductive proteins, osteoconductive scaffolds and mechanical stability. Recent study groups worldwide have been studying the Mesenchymal Stem Cells as an adjunct to increase the bone healing process. However, newer literatures have shown that only few number of MSC transplanted will integrate. This paracrine mechanism is mediated by active secretion of cytokines, growth factors and enzymes called the secretome which is produced as a byproduct during the process of MSC culture. The addition of secretome itself alone is predicted to have the similar effect as the transplantation of MSC with less cost needed, and easier to obtain. The effect of MSC secretome has shown positive result on neurodegenerative disease, acute kidney disease, and cancer; but the effect on bone regeneration itself has never been studied. The MSC secretome have been proven to contain various cytokines (TGβ, some interleukins, GCSF, and many other cytokines) and growth factors (VEGF, EGF, PDGF, IGF-1, IGF-II, PLGF, HGF, NGF, BDNF). We also suspect the osteoinductive profile of MSC secretome due to the existence of BMP-2 which can be analysed using the ELISA spectrophotometry. The osteoinductive profile of secretome MSC will be able to replace the need of recombinant human BMP-2 (rhBMP-2) transplantation in treating bone defect and diminish the risk of excessive inflammation created by BMP-2 and also the carcinogenic potency.

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Acupuncture and Auricular Acupressure in Relieving Menopausal Hot Flashes of Bilaterally Ovariectomized Chinese Women: A Randomized Controlled Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nep001 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 18

Author(s):

Jue Zhou ◽

Fan Qu ◽

Xisheng Sang ◽

Xiaotong Wang ◽

Rui Nan

Keyword(s):

Chinese Women ◽

Controlled Trial ◽

Hormone Replacement ◽

Hot Flashes ◽

Serum Levels ◽

Auricular Acupressure ◽

Significant Difference ◽

Before And After ◽

Pre Treatment

The objective of this study is to explore the effects of acupuncture and auricular acupressure in relieving menopausal hot flashes of bilaterally ovariectomized Chinese women. Between May 2006 and March 2008, 46 bilaterally ovariectomized Chinese women were randomized into an acupuncture and auricular acupressure group (n= 21) and a hormone replacement therapy (HRT) group (Tibolone,n= 25). Each patient was given a standard daily log and was required to record the frequency and severity of hot flashes and side effects of the treatment felt daily, from 1 week before the treatment started to the fourth week after the treatment ended. The serum levels of follicle stimulating hormone (FSH), LH and E2were detected before and after the treatment. After the treatment and the follow-up, both the severity and frequency of hot flashes in the two groups were relieved significantly when compared with pre-treatment (P< .05). There was no significant difference in the severity of hot flashes between them after treatment (P> .05), while after the follow-up, the severity of hot flashes in the HRT group was alleviated more. After the treatment and the follow-up, the frequency of menopausal hot flashes in the HRT group was reduced more (P< .05). After treatment, the levels of FSH decreased significantly and the levels of E2increased significantly in both groups (P< .05), and they changed more in the HRT group (P< .05). Acupuncture and auricular acupressure can be used as alternative treatments to relieve menopausal hot flashes for those bilaterally ovariectomized women who are unable or unwilling to receive HRT.

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Ifosfamide induced encephalopathy in a child with osteosarcoma

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220963545 ◽

2020 ◽

pp. 107815522096354

Author(s):

Hakan Sarbay ◽

Ülkü F. Demir ◽

Güliz Yılmaz ◽

Abdullah A. Atay ◽

Barış Malbora

Keyword(s):

Methylene Blue ◽

Case Report ◽

Treatment Protocol ◽

Supportive Therapy ◽

Neurological Findings ◽

Electrolyte Disturbances ◽

Before And After ◽

Life Threatening ◽

Reversible Encephalopathy

Background Ifosfamide (IFO) is an alkylating agent used to treat broad range of malignancies. One of the life-threatening toxic effects is reversible neurotoxicity. In this report; we presented a case report of ifosfamide induced encephalopathy (IIE) in a child with osteosarcoma in order to emphize that it is important to continue ifosfamide treatment as well as the importance of this potentially fatal complication. Case report Following the 20th week of ifosfamide treatment, the patient's follow-up with the diagnosis of osteosarcoma developed neurological findings. Laboratory analyzes before and after ifosfamide infusion were normal. No pathological findings were seen on MR imaging. Hypoglycemia, electrolyte disturbances, encephalitis, meningitis, metastasis and posterior reversible encephalopathy syndrome (PRES) were not considered. Electroencephalography was found compatible with neuronal hyperexcitability originating from the left hemisphere. With the diagnosis of ifosfamide induced encephalopathy, prophylaxis with methylene blue was received before the next infusion of ifosfamide. Neurological findings were not observed in the patient's follow-up. Conclusion Patients who develop IIE can continue their treatment protocol with methylene blue prophylaxis and supportive therapy.

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Serum Markers of Refractoriness and Enteropathy-Associated T-Cell Lymphoma in Coeliac Disease

Cancers ◽

10.3390/cancers13102289 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2289

Author(s):

Marco Vincenzo Lenti ◽

Nicola Aronico ◽

Paolo Giuffrida ◽

Valentina Antoci ◽

Giovanni Santacroce ◽

...

Keyword(s):

Coeliac Disease ◽

Serum Levels ◽

Serum Markers ◽

Upper Gastrointestinal Endoscopy ◽

Significant Difference ◽

Before And After ◽

Work Up

The persistence or recurrence of symptoms in patients with coeliac disease (CD), despite a gluten-free diet (GFD), must prompt further work-up for excluding refractory CD (RCD). The aim of this study was to assess the accuracy of serum markers in predicting refractoriness in CD patients. This study included 72 patients affected by CD followed-up at our center, namely 49 uncomplicated CD before and after GFD and 23 RCD. Serum levels of chromogranin A (CgA) and β2-microglobuline were measured at baseline and at follow-up (median time of 13 months) in each group of patients. Cut-off points for each marker were estimated to differentiate RCD from uncomplicated CD patients. Serum levels of CgA and β2-microglobuline were significantly higher in patients with RCD compared to uncomplicated CD (p < 0.001), both at baseline and at follow-up, with no significant difference between RCD type 1 and type 2. The estimated cut-off point for CgA was 90.2 ng/mL (sensitivity 83%, specificity 100%), while for β2-microglobuline it was 696 mcg/L (sensitivity 100%, specificity of 100%). To conclude, CgA and β2-microglobuline could be useful serological markers of refractoriness in CD, with the ability to discriminate those patients who should undergo upper gastrointestinal endoscopy for making a definite diagnosis.

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Immune response dynamics and Lutzomyia longipalpis exposure characterize a biosignature of visceral leishmaniasis susceptibility in a canine cohort

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009137 ◽

2021 ◽

Vol 15 (2) ◽

pp. e0009137

Author(s):

Manuela da Silva Solcà ◽

Maiara Reis Arruda ◽

Bruna Martins Macedo Leite ◽

Tiago Feitosa Mota ◽

Miriam Flores Rebouças ◽

...

Keyword(s):

Immune Response ◽

Visceral Leishmaniasis ◽

Clinical Manifestations ◽

Parasite Load ◽

Serum Levels ◽

Lutzomyia Longipalpis ◽

Response Dynamics ◽

Before And After ◽

One Year

Background Reports have shown correlations between the immune response to vector saliva and Leishmaniasis outcome. We followed dogs in an endemic area for two years characterizing resistance or susceptibility to canine visceral leishmaniasis (CVL) according to Leishmania infantum diagnosis and clinical development criteria. Then, we aimed to identify a biosignature based on parasite load, serum biological mediators’ interactions, and vector exposure intensity associated with CVL resistance and susceptibility. Methodology/Principal findings A prospective two-year study was conducted in an area endemic for CVL. Dogs were evaluated at 6-month intervals to determine infection, clinical manifestations, immune profile, and sandfly exposure. CVL resistance or susceptibility was determined upon the conclusion of the study. After two years, 78% of the dogs were infected with L. infantum (53% susceptible and 47% resistant to CVL). Susceptible dogs presented higher splenic parasite load as well as persistence of the parasite during the follow-up, compared to resistant ones. Susceptible dogs also displayed a higher number of correlations among the investigated biological mediators, before and after infection diagnosis. At baseline, anti-saliva antibodies, indicative of exposure to the vector, were detected in 62% of the dogs, reaching 100% in one year. Higher sandfly exposure increased the risk of susceptibility to CVL by 1.6 times (CI: 1.11–2.41). We identified a discriminatory biosignature between the resistant and susceptible dogs assessing splenic parasite load, interaction of biological mediators, PGE2 serum levels and intensity of exposure to sandfly. All these parameters were elevated in susceptible dogs compared to resistant animals. Conclusions/Significance The biosignature identified in our study reinforces the idea that CVL is a complex multifactorial disease that is affected by a set of factors which are correlated and, for a better understanding of CVL, should not be evaluated in an isolated way.

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Impact of the Innate Inflammatory Response on ICU Admission and Death in Hospitalized Patients with COVID-19

Biomedicines ◽

10.3390/biomedicines9111675 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1675

Author(s):

Jorge Monserrat ◽

Angel Asunsolo ◽

Ana Gómez-Lahoz ◽

Miguel A. Ortega ◽

Jose Maria Gasalla ◽

...

Keyword(s):

Growth Factors ◽

Retrospective Cohort ◽

Prognostic Value ◽

Outcome Measure ◽

Serum Levels ◽

Hospitalized Patients ◽

Icu Admission ◽

Cytokines And Chemokines ◽

Marker Combination

Objective: To describe the capacity of a broad spectrum of cytokines and growth factors to predict ICU admission and/or death in patients with severe COVID-19. Design: An observational, analytical, retrospective cohort study with longitudinal follow-up. Setting: Hospital Universitario Príncipe de Asturias (HUPA). Participants: 287 patients diagnosed with COVID-19 admitted to our hospital from 24 March to 8 May 2020, followed until 31 August 2020. Main outcome measures: Profiles of immune response (IR) mediators were determined using the Luminex Multiplex technique in hospitalized patients within six days of admission by examining serum levels of 62 soluble molecules classified into the three groups: adaptive IR-related cytokines (n = 19), innate inflammatory IR-related cytokines (n = 27), and growth factors (n = 16). Results: A statistically robust link with ICU admission and/or death was detected for increased serum levels of interleukin (IL)-6, IL-15, soluble (s) RAGE, IP10, MCP3, sIL1RII, IL-8, GCSF and MCSF and IL-10. The greatest prognostic value was observed for the marker combination IL-10, IL-6 and GCSF. Conclusions: When severe COVID-19 progresses to ICU admission and/or death there is a marked increase in serum levels of several cytokines and chemokines, mainly related to the patient’s inflammatory IR. Serum levels of IL-10, IL-6 and GCSF were most prognostic of the outcome measure.

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Chronic Osteomyelitis of the tibia and ankle treated with Limb Salvage Reconstruction

Journal of Bone and Joint Infection ◽

10.7150/jbji.40337 ◽

2019 ◽

Vol 4 (6) ◽

pp. 306-313 ◽

Cited By ~ 2

Author(s):

Aaron Lam ◽

Shawn S. Richardson ◽

Josh Buksbaum ◽

Jonathan Markowitz ◽

Michael W. Henry ◽

...

Keyword(s):

Risk Factor ◽

Diabetic Neuropathy ◽

Limb Salvage ◽

Chronic Osteomyelitis ◽

Treatment Protocol ◽

Case Series ◽

Salvage Treatment ◽

Retrospective Case ◽

Non Union

Abstract. Introduction: To confirm the success of our limb salvage treatment protocol and determine what factors are predictive of success versus failure in limb salvage techniques for patients with chronic osteomyelitis of the tibia and ankle.Methods: Retrospective case series analyzing factors and outcomes in patients who underwent limb salvage techniques for chronic osteomyelitis of tibia or ankle. Main outcome measurements included infection controlled without the need for amputation or chronic antibiotic suppression and union of infected non-unions.Results: Mean follow-up was 3.9 years. Out of the sixty-seven patients (mean age: 51.4 years) treated for chronic osteomyelitis, fifty-four had an associated non-union. Sixty-one patients (91.0%) had their infection controlled by limb salvage. Five ultimately required amputation and one remained on daily chronic antibiotics. Diabetics complicated with neuropathy and increasing numbers of limb salvage surgeries were associated with a significantly higher failure rate. Forty-eight out of fifty-four patients (88.9%) also had successful healing of their infected non-union. Diabetes and need for more limb salvage surgeries were also found to have a significantly higher failure rate.Conclusions: Limb salvage is a reliable and successful treatment for patients with chronic osteomyelitis and infected non-unions of the lower extremities. Diabetic neuropathy is a risk factor that impedes success.Level of Evidence: Prognostic Level IV.

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