José Guzman-Esquivel | INSTITUTO MEXICANO DEL SEGURO SOCIAL (original) (raw)

Papers by José Guzman-Esquivel

Research paper thumbnail of Empirical Antibiotic Prescribing in Adult COVID-19 Inpatients over Two Years in Mexico

Antibiotics

Background and Objectives: Empirical antibiotic prescribing in patients with coronavirus disease ... more Background and Objectives: Empirical antibiotic prescribing in patients with coronavirus disease 2019 (COVID-19) has been common even though bacterial coinfections are infrequent. The overuse of antibacterial agents may accelerate the antibiotic resistance crisis. We aimed to evaluate factors predicting empirical antibiotic prescribing to adult COVID-19 inpatients over 2 years (March 2020–February 2021) in Mexico. Materials and Methods: A cross-sectional analysis of a nationwide cohort study was conducted. Hospitalized adults due to laboratory-confirmed COVID-19 were included (n = 214,171). Odds ratios (OR) and 95% confidence intervals (CI), computed by using logistic regression models, were used to evaluate factors predicting empirical antibiotic prescribing. Results: The overall frequency of antibiotic usage was 25.3%. In multiple analysis, the highest risk of antibiotic prescription was documented among patients with pneumonia at hospital admission (OR = 2.20, 95% CI 2.16–2.25). ...

Research paper thumbnail of “I prefer to get coronavirus than to stop working”: the street vendor’s perspective

The Journal of Infection in Developing Countries, 2021

During phase 2 of the COVID-19 pandemic in a Mexican City, informal street vendors (cases) and fo... more During phase 2 of the COVID-19 pandemic in a Mexican City, informal street vendors (cases) and formal employees (controls) were interviewed. A total of 82.6% of street vendors preferred to expose themselves to the coronavirus than to stop working, compared with 18.4% of formal employees (adjusted OR = 19.4, 95%CI: 4.6-81.7, p < 0.001). Street vendors had 7 times less fear of dying from coronavirus (adjusted OR = 0.14, 95% CI: 0.03-0.5, p = 0.005) and showed a 16-times greater lack of real concern for the increase in cases in their community than the formal employees (adjusted OR = 0.06, 95% CI: 0.01-0.3, p = 0.002). Street vendors were the group with the poorest adherence to household and work area containment measures that continued to be in contact with others. The corresponding authorities must plan specific strategies that allow street vendors to survive economically, while at the same time, protecting community health.

Research paper thumbnail of A novel cell-free formulation for the treatment of knee osteoarthritis generates better patient-reported health outcomes in more severe cases

Journal of Orthopaedic Surgery, 2020

Background: The bioactive cell-free formulation (BIOF2) for cartilage regeneration has shown a ma... more Background: The bioactive cell-free formulation (BIOF2) for cartilage regeneration has shown a major therapeutic response in severe knee osteoarthritis. However, its effect on patients with mild or moderate stages of the disease has not been studied. Objective: To evaluate the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, minimal clinically important improvement (MCII) and sleep disturbances in mild, moderate, and severe stages of knee osteoarthritis (OA) with the novel cell-free formulation treatment (BIOF2). Methods: An open-label, nonrandomized, baseline-controlled, parallel group study on patients with mild, moderate, and severe knee OA was conducted to evaluate the effect of intra-articular administration of BIOF2. Clinical improvement was determined through the WOMAC score and MCII, whereas sleep disturbances were measured through a Likert scale questionnaire. Results: At 6 months post-treatment, the mean decrease in the total WOMAC score was 16...

Research paper thumbnail of Patient‑reported health outcomes for severe knee osteoarthritis after conservative treatment with an intra‑articular cell‑free formulation for articular cartilage regeneration combined with usual medical care vs. usual medical care alone: A randomized controlled trial

Experimental and Therapeutic Medicine, 2019

Osteoarthritis (OA) is a major public health problem characterized by joint pain, fatigue, functi... more Osteoarthritis (OA) is a major public health problem characterized by joint pain, fatigue, functional limitation and decreased quality of life of the patient, which results in increased use of healthcare services and high economical costs. A promising novel bioactive cell-free formulation (BIOF2) for cartilage regeneration has recently been tested in pre-clinical and clinical trials, and has demonstrated a success rate similar to that of total joint arthroplasty for the treatment of severe knee OA. The present study evaluated the efficacy of treatment with BIOF2, by including it within a conservative regimen of 'usual medical care' of knee OA, and whether its efficacy was affected in subgroups of patients presenting with comorbidities that exacerbate OA. A prospective, randomized, 2-arm parallel group phase III clinical trial was conducted, which included 105 patients in the 'usual medical care' group (paracetamol/NSAIDs and general care provided by the family physician) and 107 patients in the BIOF2 group (usual medical care + intra-articular BIOF2 application at 0, 1 and 2 months). Two aspects were evaluated at 0, 6 and 12 months: i) Minimal clinically important improvement (MCII), based on 30% improvement of pain from the baseline; and ii) the Patient Acceptable Symptom State (PASS), a questionnaire that determines patient well-being thresholds for articular pain and function. Adverse effects and regular NSAID use were registered. At 12 months, BIOF-2 treatment produced MCII in 70% of the patients and >50% achieved PASS. Excluding the patients with class 2 obesity or malalignment conditions (genu varum or genu valgum >20 degrees), the experimental treatment produced MCII and PASS in 100 and 92% of patients, respectively, compared with 25 and 8% in the group of usual medical care (P<0.001). No patient with malalignment and treatment with BIOF2 achieved PASS. Notably, there were no serious adverse effects. To conclude, BIOF2 is a safe therapeutic alternative that is easy to implement together with usual medical care for knee OA. Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000277. Retrospectively registered June, 2018.

Research paper thumbnail of Adenovirus 5 produces obesity and adverse metabolic, morphological, and functional changes in the long term in animals fed a balanced diet or a high-fat diet: a study on hamsters

Archives of Virology, 2019

Adenovirus 5 (Ad-5) infection is a common cause of acute respiratory infections and the main vect... more Adenovirus 5 (Ad-5) infection is a common cause of acute respiratory infections and the main vector used in gene therapy. There are few studies on the relationship of Ad-5 to obesity. In the present study, we evaluated the chronic effects of Ad-5 infection on golden (Syrian) hamsters fed either a balanced diet (BD) or a high-fat diet (HFD). After a single inoculation with Ad-5 (1 × 10 7 pfu), the body weight of the animals was measured weekly. Medium-term (22 weeks) serum biochemical analyses and long-term (44 weeks) liver morphology, adiposity, and locomotive functionality (movement velocity) assessments were carried out. In the animals fed the BD, adenovirus infection produced hyperglycemia and hyperlipidemia. In the long term, it produced a 57% increase in epididymal pad fat and a 30% body weight gain compared with uninoculated animals. In addition, morphological changes related to non-alcoholic fatty liver disease (NAFLD) were observed. The animals fed the HFD had similar but more severe changes. In addition, the hamsters presented an obesity paradox: at the end of the study, the animals that had the most morphological and functional changes (significantly reduced movement velocity) had the lowest body weight. Despite the fact that an HFD appears to be a more harmful factor in the long term than adenovirus infection alone, infection could increase the severity of harmful effects in individuals with an HFD. Epidemiological studies are needed to evaluate the effect of adenovirus as a precursor of chronic liver and cardiovascular diseases, including the chronic effects of gene therapy.

Research paper thumbnail of Topical 5% potassium permanganate solution accelerates the healing process in chronic diabetic foot ulcers

Biomedical reports, 2018

Potassium permanganate has been reported to be an effective treatment for certain types of wounds... more Potassium permanganate has been reported to be an effective treatment for certain types of wounds. The aim of the present study was to evaluate the use of potassium permanganate in the treatment of diabetic foot ulcers. A single-blind, randomized, controlled clinical trial was conducted on patients with type 2 diabetes mellitus that presented with a foot ulcer persisting for >3 months. The control group (n=10) was treated with the current standard treatment, which comprises of measures for reducing pressure in the ulcerated area, daily cleansing of the ulcer with potable water and antiseptic wash solution, and the application of a disinfectant solution on the entire surface area of the ulcer; while the intervention group (n=15) received the standard treatment plus 5% topical potassium permanganate solution applied once a day for 21 days. In the intervention group, 1 patient did not tolerate the treatment and was eliminated from the study on the first day. The remaining patients t...

Research paper thumbnail of Smoking and female sex as key risk factors associated with severe arthralgia in acute and chronic phases of Chikungunya virus infection

Experimental and therapeutic medicine, 2018

Arthralgia is a potentially incapacitating condition and a persistent symptom in chronic or acute... more Arthralgia is a potentially incapacitating condition and a persistent symptom in chronic or acute episodes of Chikungunya fever caused by infection with the Chikungunya virus (CHIKV). To the best of our knowledge, there are no reports on risk factors associated with the intensity of arthralgias in typical acute episodes of the disease. Although a number of studies have reported on risk factors associated with the development of the chronic stage of the disease, smoking habits have not been analyzed. Smoking is an interesting factor to consider since it is the main environmental risk factor for the development of rheumatoid arthritis (RA), a similar disease to CHIKV in many aspects. In the present study, 140 patients infected with CHIKV were assessed for risk factors associated with severe arthralgia intensity in the acute phase (pain of 9/10 on the visual analog scale of 0-10) and moderate to severe intensity (according to the Routine Assessment of Patient Index Data 3) 3.5 months a...

Research paper thumbnail of A phase I–II controlled randomized trial using a promising novel cell-free formulation for articular cartilage regeneration as treatment of severe osteoarthritis of the knee

European Journal of Medical Research, 2018

BackgroundA promising novel cell-free bioactive formulation for articular cartilage regeneration,... more BackgroundA promising novel cell-free bioactive formulation for articular cartilage regeneration, called BIOF2, has recently been tested in pre-clinical trials. The aim of the present study was to evaluate the efficacy and safety of BIOF2 for intra-articular application in patients with severe osteoarthritis of the knee.MethodsA prospective, randomized, 3-arm, parallel group clinical trial was conducted. It included 24 patients with severe osteoarthritis of the knee (WOMAC score 65.9 ± 17). Before they entered the study, all the patients were under osteoarthritis control through the standard treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed by their family physician. Patients were distributed into three groups of 8 patients each (intra-articular BIOF2, total joint arthroplasty, or conservative treatment with NSAIDs alone). The WOMAC score, RAPID3 score, and Rasmussen clinical score were evaluated before treatment and at months 3, 6, and 12. BIOF2 was applied a...

Research paper thumbnail of A promising novel formulation for articular cartilage regeneration: Preclinical evaluation of a treatment that produces SOX9 overexpression in human synovial fluid cells

Molecular medicine reports, Jan 20, 2017

Osteoarthritis (OA) is a chronic disorder of synovial joints, in which there is progressive softe... more Osteoarthritis (OA) is a chronic disorder of synovial joints, in which there is progressive softening and disintegration of the articular cartilage. OA is the most common form of arthritis, and is the primary cause of disability and impaired quality of life in the elderly. Despite considerable medical necessity, no treatment has yet been proven to act as a disease‑modifying agent that may halt or reverse the structural progression of OA. The replacement of the joint with a prosthesis appears to be the best option in the advanced stages of the disease. A formulation (BIOF2) for cartilage regeneration has been recently developed. The present study evaluated the effects of BIOF2 on gene expression in human cell cultures, followed by efficacy trials in three OA animal models. Human synovial fluid cells that were exposed to the formulation exhibited increased transcription factor SOX‑9 (SOX9; chondrogenic factor) expression, and decreased mimecan (mineralization inducer) and macrophage‑s...

Research paper thumbnail of Dengue virus-1 NS5 genetic variant associated with a severe clinical infection: Possible reduction of the innate immune response by inhibition of interferon type 1 and the Janus kinase-signal transducer and activator of transcription signaling pathway

International journal of molecular medicine, Jan 17, 2018

Dengue virus (DENV) is currently considered as one of the most important mosquito-borne viral pat... more Dengue virus (DENV) is currently considered as one of the most important mosquito-borne viral pathogens affecting humans. Genetic variations in viruses are likely to be a condition for more effective evasion of the immune system and resulting in severe clinical consequences. The DENV‑1 NS5 gene was sequenced to establish whether during an epidemic burst there were genetic variations of the virus and whether any variant was associated (through a case‑control design) with severe clinical behavior. A total of 31 patients positive for DENV‑1 were enrolled. Among the nucleotide differences between the sequences, only two generated amino acid changes. The variants 124Met/166Ser (amino acid positions according to the report GenBank AJL35015.1), were associated with a severe clinical course of the disease. Via in silico tests, it was identified that the variations generate changes in the protein probably affecting the function of type‑1 interferon, either at the level of its receptor or by ...

Research paper thumbnail of Preclinical analysis of nonsteroidal anti-inflammatory drug usefulness for the simultaneous prevention of steatohepatitis, atherosclerosis and hyperlipidemia

International journal of clinical and experimental medicine, 2015

Nonalcoholic steatohepatitis (NASH) is currently one of the primary liver diseases. Recent studie... more Nonalcoholic steatohepatitis (NASH) is currently one of the primary liver diseases. Recent studies have shown a clinical relation between NASH and atherosclerosis. There is much interest in these two diseases because they are both associated with great morbidity and mortality. Inflammation and the overexpression of COX-2 participate in the pathophysiology of the two diseases, and therefore simultaneous treatment is feasible. The role of the four NSAIDs, meclofenamate, mefenamate, flufenamate, and aspirin, was analyzed in a mouse model of NASH, as well as preclinical atherosclerosis induced by a high-fat diet (HFD). Six mouse groups were formed. Five of the groups were fed a high-fat diet for 6 months and one group was fed a standard diet, acting as the normality reference. Of the five groups fed a high-fat diet, four received a NSAID, each of them identified by the specific drug administered. One group received no treatment. Serum markers (cholesterol, triglycerides, ALT, and AST) a...

Research paper thumbnail of Association of Milk and Meat Consumption with the Development of Breast Cancer in a Western Mexican Population

Breast Care, 2015

Background: Breast cancer is a public health problem and it is the most common gynecologic neopla... more Background: Breast cancer is a public health problem and it is the most common gynecologic neoplasia worldwide. The risk factors for its development are of both hereditary and environmental origin. Certain foods have been clearly associated with modifying the breast cancer risk. The aim of the present analysis was to evaluate the effects of cow's milk and meat consumption on the development of breast cancer in a population from Western Mexico (Colima). Material and Methods: We studied 97 patients presenting with a histopathologic diagnosis of breast cancer and 104 control individuals who did not present with the disease (Breast Imaging Report and Data System (BI-RADS) 1-2). 80% of the population belonged to a low socioeconomic stratum. The main clinical characteristics were analyzed along with the lifetime consumption of meat and milk. Results: High milk consumption increased the breast cancer risk by 7.2 times (p = 0.008) whereas the consumption of meat was not significantly as...

Research paper thumbnail of Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

Oncology Letters, 2015

Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. ... more Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated in vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10-40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50-90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug.

Research paper thumbnail of Protective effect of doxycycline on germinal epithelial loss caused by a high-fat diet

International Urology and Nephrology, 2013

A high-fat diet and male obesity are aspects associated with germinal epithelial alterations and ... more A high-fat diet and male obesity are aspects associated with germinal epithelial alterations and male infertility. Some reports have shown that certain tetracyclines can protect the germinal epithelium from toxic drugs. The aim of the present study design was to evaluate the possible effect of doxycycline on testicular germ cells in individuals fed a Western diet (atherogenic), using a murine model. Two groups of male mice (BALB/c) were fed a high-fat Western diet (HFD). One of these two groups was given doxycycline at a dose of 10 mg/kg/day (HFD+Dox). A third group was fed a standard rodent diet (SD group). After 6 months, the mice were euthanized and morphologic and histopathologic analyses were performed. Germinal epithelial height was similar between the SD group (54 μm) and the HFD+Dox group (53 μm) (p = 0.26), and it was significantly reduced in the HFD group (47 μm) (p = 0.0001). The degree of germinal epithelial loss (DGEL) was significantly lower in the SD (10) and HFD+Dox (12.5) groups than in the HFD group (30) (p = 0.0001 and =0.007, respectively). There were no differences in the DGEL between the SD and HFD+Dox groups (p = 0.42). Doxycycline administration was shown to prevent germinal epithelial loss in the testes of mice fed a high-fat diet. Future studies are necessary to evaluate the clinical usefulness of doxycycline or its analogs in persons with a habitual high-fat diet.

Research paper thumbnail of Reply to the comments of Kathpalia et al. to the article: effect of intraprostatic epinephrine on intraoperative blood loss reduction during transurethral resection of the prostate

International Urology and Nephrology, 2012

Research paper thumbnail of A dramatic case of genital radionecrosis

International Urology and Nephrology, 2009

Background Epidermoid carcinoma of the penis presents in 1% of malignant tumors in men. Penis can... more Background Epidermoid carcinoma of the penis presents in 1% of malignant tumors in men. Penis cancer treatment has traditionally been total or partial amputation. There are authors who consider radiation to be part of penis cancer treatment in select casesespecially the use of brachytherapy and external radiation. Clinical case The case of a 48-year-old male who in 2004 presented with an ulcerated lesion of the penis that was left unattended to is presented. Two years later, he sought medical attention and physical examination revealed an ulcerated penile lesion with poorly defined edges and limited to the glans. Diagnosis The lesion was biopsied and the histopathological study reported Epidermoid Carcinoma. After radiological studies, it was classified as stage T2-N0-M0. Treatment Total penectomy without lymphadenectomy was performed. The patient received adjuvant treatment of 15 sessions of cobalt radiation treatment at a dose of 3,500 cGy. Six months later, the patient noticed the presence of erythema at the genital and inguinal level which later ulcerated and extended toward the perineum. The disease progressed tragically and the patient died 2 years later.

Research paper thumbnail of Effect of intraprostatic epinephrine on intraoperative blood loss reduction during transurethral resection of the prostate

International Urology and Nephrology, 2012

Objective To determine whether the use of intraprostatic epinephrine during transurethral resecti... more Objective To determine whether the use of intraprostatic epinephrine during transurethral resection of the prostate reduces intraoperative blood loss. Methods A random, double-blind, prospective study was carried out on twenty-three patients that underwent transurethral resection of the prostate. Patients were divided into two groups: (1) group receiving intraoperative intraprostatic injection of epinephrine (thirteen patients) and (2) group receiving intraoperative intraprostatic injection of saline solution as placebo (ten patients). Blood loss was quantified with the following formula: irrigation solution hemoglobin 9 1000/intraoperative presurgical serum hemoglobin. The variables analyzed were blood loss, resection time, presurgical prostate volume, and grams of resected tissue. Students t test and Pearson correlation were used for their analysis. Results There were thirteen patients in the epinephrine group and ten patients in the placebo group. Mean blood loss in the epinephrine group was significantly lower than in the placebo group (127.48 mL ± 77.0 mL vs. 336.63 ± 185.6 mL, 95% CI, 45-234, P \ 0.001). There were no statistically significant differences in mean resected grams or mean resection time between the two groups. One patient in the epinephrine group presented with intraoperative hypertensive crisis (7.7%). Conclusions Intraprostatic epinephrine injection can be used to reduce blood loss during transurethral resection of the prostate in selected patients. Cardiovascular monitoring should be carried out during its application. Resection time and grams of resected tissue continue to be the most influential factors in relation to blood loss in patients undergoing this treatment modality.

Research paper thumbnail of Antitumor effect of meclofenamic acid on human androgen-independent prostate cancer: a preclinical evaluation

International Urology and Nephrology, 2011

Purpose Prostate cancer is a worldwide public health problem and its treatment continues to be a ... more Purpose Prostate cancer is a worldwide public health problem and its treatment continues to be a therapeutic challenge especially in patients with metastatic androgen-independent cancer. Inflammation is a process that has been involved in the origin of this cancer and its inhibition has been postulated as a prophylactic and therapeutic strategy. The present study evaluated two non-steroidal anti-inflammatory drugs (meclofenamic acid and mefenamic acid) that have been studied very little in regard to cancer treatment. Methods In vitro, the cytotoxic effects of meclofenamic acid and mefenamic acid were determined in human prostate cancer cell lines (LNCaP: androgendependent; and PC3: androgen-independent). In vivo trials were divided into two phases; meclofenamic acid toxicity was initially determined at different doses (0, 5, 10 and 20 mg/kg/day/25 days) in BALB/ c mice, after which a trial using non-toxic doses was carried out to evaluate the antitumor efficacy of the drug in a PC3/nude-mouse model of human androgen-independent prostate cancer. Results In vitro trials showed that only meclofenamic acid is highly cytotoxic in neoplastic prostate cells. The 5 and 10 mg/kg/day/25 day doses did not cause relevant toxicity in the BALB/c mouse trial, and so both doses were used in the nude-mouse model of cancer trial. This latter trial showed that meclofenamic acid significantly reduces tumor growth, prolongs survival, and is even capable of generating

Research paper thumbnail of Association between human papillomavirus in men and their sexual partners and uterine cervical intraepithelial neoplasia

International Urology and Nephrology, 2008

Objectives To determine whether the presence of human papillomavirus (HPV) in men is a risk facto... more Objectives To determine whether the presence of human papillomavirus (HPV) in men is a risk factor in the development of intraepithelial cervical neoplasia in their sexual partners and to corroborate HPV frequency and type. Materials and methods A case-control study was carried out in the city of Colima, Mexico, from

Research paper thumbnail of Metalloproteinase-1 usefulness in urethral stricture treatment

International Urology and Nephrology, 2011

Research paper thumbnail of Empirical Antibiotic Prescribing in Adult COVID-19 Inpatients over Two Years in Mexico

Antibiotics

Background and Objectives: Empirical antibiotic prescribing in patients with coronavirus disease ... more Background and Objectives: Empirical antibiotic prescribing in patients with coronavirus disease 2019 (COVID-19) has been common even though bacterial coinfections are infrequent. The overuse of antibacterial agents may accelerate the antibiotic resistance crisis. We aimed to evaluate factors predicting empirical antibiotic prescribing to adult COVID-19 inpatients over 2 years (March 2020–February 2021) in Mexico. Materials and Methods: A cross-sectional analysis of a nationwide cohort study was conducted. Hospitalized adults due to laboratory-confirmed COVID-19 were included (n = 214,171). Odds ratios (OR) and 95% confidence intervals (CI), computed by using logistic regression models, were used to evaluate factors predicting empirical antibiotic prescribing. Results: The overall frequency of antibiotic usage was 25.3%. In multiple analysis, the highest risk of antibiotic prescription was documented among patients with pneumonia at hospital admission (OR = 2.20, 95% CI 2.16–2.25). ...

Research paper thumbnail of “I prefer to get coronavirus than to stop working”: the street vendor’s perspective

The Journal of Infection in Developing Countries, 2021

During phase 2 of the COVID-19 pandemic in a Mexican City, informal street vendors (cases) and fo... more During phase 2 of the COVID-19 pandemic in a Mexican City, informal street vendors (cases) and formal employees (controls) were interviewed. A total of 82.6% of street vendors preferred to expose themselves to the coronavirus than to stop working, compared with 18.4% of formal employees (adjusted OR = 19.4, 95%CI: 4.6-81.7, p < 0.001). Street vendors had 7 times less fear of dying from coronavirus (adjusted OR = 0.14, 95% CI: 0.03-0.5, p = 0.005) and showed a 16-times greater lack of real concern for the increase in cases in their community than the formal employees (adjusted OR = 0.06, 95% CI: 0.01-0.3, p = 0.002). Street vendors were the group with the poorest adherence to household and work area containment measures that continued to be in contact with others. The corresponding authorities must plan specific strategies that allow street vendors to survive economically, while at the same time, protecting community health.

Research paper thumbnail of A novel cell-free formulation for the treatment of knee osteoarthritis generates better patient-reported health outcomes in more severe cases

Journal of Orthopaedic Surgery, 2020

Background: The bioactive cell-free formulation (BIOF2) for cartilage regeneration has shown a ma... more Background: The bioactive cell-free formulation (BIOF2) for cartilage regeneration has shown a major therapeutic response in severe knee osteoarthritis. However, its effect on patients with mild or moderate stages of the disease has not been studied. Objective: To evaluate the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, minimal clinically important improvement (MCII) and sleep disturbances in mild, moderate, and severe stages of knee osteoarthritis (OA) with the novel cell-free formulation treatment (BIOF2). Methods: An open-label, nonrandomized, baseline-controlled, parallel group study on patients with mild, moderate, and severe knee OA was conducted to evaluate the effect of intra-articular administration of BIOF2. Clinical improvement was determined through the WOMAC score and MCII, whereas sleep disturbances were measured through a Likert scale questionnaire. Results: At 6 months post-treatment, the mean decrease in the total WOMAC score was 16...

Research paper thumbnail of Patient‑reported health outcomes for severe knee osteoarthritis after conservative treatment with an intra‑articular cell‑free formulation for articular cartilage regeneration combined with usual medical care vs. usual medical care alone: A randomized controlled trial

Experimental and Therapeutic Medicine, 2019

Osteoarthritis (OA) is a major public health problem characterized by joint pain, fatigue, functi... more Osteoarthritis (OA) is a major public health problem characterized by joint pain, fatigue, functional limitation and decreased quality of life of the patient, which results in increased use of healthcare services and high economical costs. A promising novel bioactive cell-free formulation (BIOF2) for cartilage regeneration has recently been tested in pre-clinical and clinical trials, and has demonstrated a success rate similar to that of total joint arthroplasty for the treatment of severe knee OA. The present study evaluated the efficacy of treatment with BIOF2, by including it within a conservative regimen of 'usual medical care' of knee OA, and whether its efficacy was affected in subgroups of patients presenting with comorbidities that exacerbate OA. A prospective, randomized, 2-arm parallel group phase III clinical trial was conducted, which included 105 patients in the 'usual medical care' group (paracetamol/NSAIDs and general care provided by the family physician) and 107 patients in the BIOF2 group (usual medical care + intra-articular BIOF2 application at 0, 1 and 2 months). Two aspects were evaluated at 0, 6 and 12 months: i) Minimal clinically important improvement (MCII), based on 30% improvement of pain from the baseline; and ii) the Patient Acceptable Symptom State (PASS), a questionnaire that determines patient well-being thresholds for articular pain and function. Adverse effects and regular NSAID use were registered. At 12 months, BIOF-2 treatment produced MCII in 70% of the patients and >50% achieved PASS. Excluding the patients with class 2 obesity or malalignment conditions (genu varum or genu valgum >20 degrees), the experimental treatment produced MCII and PASS in 100 and 92% of patients, respectively, compared with 25 and 8% in the group of usual medical care (P<0.001). No patient with malalignment and treatment with BIOF2 achieved PASS. Notably, there were no serious adverse effects. To conclude, BIOF2 is a safe therapeutic alternative that is easy to implement together with usual medical care for knee OA. Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000277. Retrospectively registered June, 2018.

Research paper thumbnail of Adenovirus 5 produces obesity and adverse metabolic, morphological, and functional changes in the long term in animals fed a balanced diet or a high-fat diet: a study on hamsters

Archives of Virology, 2019

Adenovirus 5 (Ad-5) infection is a common cause of acute respiratory infections and the main vect... more Adenovirus 5 (Ad-5) infection is a common cause of acute respiratory infections and the main vector used in gene therapy. There are few studies on the relationship of Ad-5 to obesity. In the present study, we evaluated the chronic effects of Ad-5 infection on golden (Syrian) hamsters fed either a balanced diet (BD) or a high-fat diet (HFD). After a single inoculation with Ad-5 (1 × 10 7 pfu), the body weight of the animals was measured weekly. Medium-term (22 weeks) serum biochemical analyses and long-term (44 weeks) liver morphology, adiposity, and locomotive functionality (movement velocity) assessments were carried out. In the animals fed the BD, adenovirus infection produced hyperglycemia and hyperlipidemia. In the long term, it produced a 57% increase in epididymal pad fat and a 30% body weight gain compared with uninoculated animals. In addition, morphological changes related to non-alcoholic fatty liver disease (NAFLD) were observed. The animals fed the HFD had similar but more severe changes. In addition, the hamsters presented an obesity paradox: at the end of the study, the animals that had the most morphological and functional changes (significantly reduced movement velocity) had the lowest body weight. Despite the fact that an HFD appears to be a more harmful factor in the long term than adenovirus infection alone, infection could increase the severity of harmful effects in individuals with an HFD. Epidemiological studies are needed to evaluate the effect of adenovirus as a precursor of chronic liver and cardiovascular diseases, including the chronic effects of gene therapy.

Research paper thumbnail of Topical 5% potassium permanganate solution accelerates the healing process in chronic diabetic foot ulcers

Biomedical reports, 2018

Potassium permanganate has been reported to be an effective treatment for certain types of wounds... more Potassium permanganate has been reported to be an effective treatment for certain types of wounds. The aim of the present study was to evaluate the use of potassium permanganate in the treatment of diabetic foot ulcers. A single-blind, randomized, controlled clinical trial was conducted on patients with type 2 diabetes mellitus that presented with a foot ulcer persisting for >3 months. The control group (n=10) was treated with the current standard treatment, which comprises of measures for reducing pressure in the ulcerated area, daily cleansing of the ulcer with potable water and antiseptic wash solution, and the application of a disinfectant solution on the entire surface area of the ulcer; while the intervention group (n=15) received the standard treatment plus 5% topical potassium permanganate solution applied once a day for 21 days. In the intervention group, 1 patient did not tolerate the treatment and was eliminated from the study on the first day. The remaining patients t...

Research paper thumbnail of Smoking and female sex as key risk factors associated with severe arthralgia in acute and chronic phases of Chikungunya virus infection

Experimental and therapeutic medicine, 2018

Arthralgia is a potentially incapacitating condition and a persistent symptom in chronic or acute... more Arthralgia is a potentially incapacitating condition and a persistent symptom in chronic or acute episodes of Chikungunya fever caused by infection with the Chikungunya virus (CHIKV). To the best of our knowledge, there are no reports on risk factors associated with the intensity of arthralgias in typical acute episodes of the disease. Although a number of studies have reported on risk factors associated with the development of the chronic stage of the disease, smoking habits have not been analyzed. Smoking is an interesting factor to consider since it is the main environmental risk factor for the development of rheumatoid arthritis (RA), a similar disease to CHIKV in many aspects. In the present study, 140 patients infected with CHIKV were assessed for risk factors associated with severe arthralgia intensity in the acute phase (pain of 9/10 on the visual analog scale of 0-10) and moderate to severe intensity (according to the Routine Assessment of Patient Index Data 3) 3.5 months a...

Research paper thumbnail of A phase I–II controlled randomized trial using a promising novel cell-free formulation for articular cartilage regeneration as treatment of severe osteoarthritis of the knee

European Journal of Medical Research, 2018

BackgroundA promising novel cell-free bioactive formulation for articular cartilage regeneration,... more BackgroundA promising novel cell-free bioactive formulation for articular cartilage regeneration, called BIOF2, has recently been tested in pre-clinical trials. The aim of the present study was to evaluate the efficacy and safety of BIOF2 for intra-articular application in patients with severe osteoarthritis of the knee.MethodsA prospective, randomized, 3-arm, parallel group clinical trial was conducted. It included 24 patients with severe osteoarthritis of the knee (WOMAC score 65.9 ± 17). Before they entered the study, all the patients were under osteoarthritis control through the standard treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed by their family physician. Patients were distributed into three groups of 8 patients each (intra-articular BIOF2, total joint arthroplasty, or conservative treatment with NSAIDs alone). The WOMAC score, RAPID3 score, and Rasmussen clinical score were evaluated before treatment and at months 3, 6, and 12. BIOF2 was applied a...

Research paper thumbnail of A promising novel formulation for articular cartilage regeneration: Preclinical evaluation of a treatment that produces SOX9 overexpression in human synovial fluid cells

Molecular medicine reports, Jan 20, 2017

Osteoarthritis (OA) is a chronic disorder of synovial joints, in which there is progressive softe... more Osteoarthritis (OA) is a chronic disorder of synovial joints, in which there is progressive softening and disintegration of the articular cartilage. OA is the most common form of arthritis, and is the primary cause of disability and impaired quality of life in the elderly. Despite considerable medical necessity, no treatment has yet been proven to act as a disease‑modifying agent that may halt or reverse the structural progression of OA. The replacement of the joint with a prosthesis appears to be the best option in the advanced stages of the disease. A formulation (BIOF2) for cartilage regeneration has been recently developed. The present study evaluated the effects of BIOF2 on gene expression in human cell cultures, followed by efficacy trials in three OA animal models. Human synovial fluid cells that were exposed to the formulation exhibited increased transcription factor SOX‑9 (SOX9; chondrogenic factor) expression, and decreased mimecan (mineralization inducer) and macrophage‑s...

Research paper thumbnail of Dengue virus-1 NS5 genetic variant associated with a severe clinical infection: Possible reduction of the innate immune response by inhibition of interferon type 1 and the Janus kinase-signal transducer and activator of transcription signaling pathway

International journal of molecular medicine, Jan 17, 2018

Dengue virus (DENV) is currently considered as one of the most important mosquito-borne viral pat... more Dengue virus (DENV) is currently considered as one of the most important mosquito-borne viral pathogens affecting humans. Genetic variations in viruses are likely to be a condition for more effective evasion of the immune system and resulting in severe clinical consequences. The DENV‑1 NS5 gene was sequenced to establish whether during an epidemic burst there were genetic variations of the virus and whether any variant was associated (through a case‑control design) with severe clinical behavior. A total of 31 patients positive for DENV‑1 were enrolled. Among the nucleotide differences between the sequences, only two generated amino acid changes. The variants 124Met/166Ser (amino acid positions according to the report GenBank AJL35015.1), were associated with a severe clinical course of the disease. Via in silico tests, it was identified that the variations generate changes in the protein probably affecting the function of type‑1 interferon, either at the level of its receptor or by ...

Research paper thumbnail of Preclinical analysis of nonsteroidal anti-inflammatory drug usefulness for the simultaneous prevention of steatohepatitis, atherosclerosis and hyperlipidemia

International journal of clinical and experimental medicine, 2015

Nonalcoholic steatohepatitis (NASH) is currently one of the primary liver diseases. Recent studie... more Nonalcoholic steatohepatitis (NASH) is currently one of the primary liver diseases. Recent studies have shown a clinical relation between NASH and atherosclerosis. There is much interest in these two diseases because they are both associated with great morbidity and mortality. Inflammation and the overexpression of COX-2 participate in the pathophysiology of the two diseases, and therefore simultaneous treatment is feasible. The role of the four NSAIDs, meclofenamate, mefenamate, flufenamate, and aspirin, was analyzed in a mouse model of NASH, as well as preclinical atherosclerosis induced by a high-fat diet (HFD). Six mouse groups were formed. Five of the groups were fed a high-fat diet for 6 months and one group was fed a standard diet, acting as the normality reference. Of the five groups fed a high-fat diet, four received a NSAID, each of them identified by the specific drug administered. One group received no treatment. Serum markers (cholesterol, triglycerides, ALT, and AST) a...

Research paper thumbnail of Association of Milk and Meat Consumption with the Development of Breast Cancer in a Western Mexican Population

Breast Care, 2015

Background: Breast cancer is a public health problem and it is the most common gynecologic neopla... more Background: Breast cancer is a public health problem and it is the most common gynecologic neoplasia worldwide. The risk factors for its development are of both hereditary and environmental origin. Certain foods have been clearly associated with modifying the breast cancer risk. The aim of the present analysis was to evaluate the effects of cow's milk and meat consumption on the development of breast cancer in a population from Western Mexico (Colima). Material and Methods: We studied 97 patients presenting with a histopathologic diagnosis of breast cancer and 104 control individuals who did not present with the disease (Breast Imaging Report and Data System (BI-RADS) 1-2). 80% of the population belonged to a low socioeconomic stratum. The main clinical characteristics were analyzed along with the lifetime consumption of meat and milk. Results: High milk consumption increased the breast cancer risk by 7.2 times (p = 0.008) whereas the consumption of meat was not significantly as...

Research paper thumbnail of Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

Oncology Letters, 2015

Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. ... more Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated in vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10-40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50-90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug.

Research paper thumbnail of Protective effect of doxycycline on germinal epithelial loss caused by a high-fat diet

International Urology and Nephrology, 2013

A high-fat diet and male obesity are aspects associated with germinal epithelial alterations and ... more A high-fat diet and male obesity are aspects associated with germinal epithelial alterations and male infertility. Some reports have shown that certain tetracyclines can protect the germinal epithelium from toxic drugs. The aim of the present study design was to evaluate the possible effect of doxycycline on testicular germ cells in individuals fed a Western diet (atherogenic), using a murine model. Two groups of male mice (BALB/c) were fed a high-fat Western diet (HFD). One of these two groups was given doxycycline at a dose of 10 mg/kg/day (HFD+Dox). A third group was fed a standard rodent diet (SD group). After 6 months, the mice were euthanized and morphologic and histopathologic analyses were performed. Germinal epithelial height was similar between the SD group (54 μm) and the HFD+Dox group (53 μm) (p = 0.26), and it was significantly reduced in the HFD group (47 μm) (p = 0.0001). The degree of germinal epithelial loss (DGEL) was significantly lower in the SD (10) and HFD+Dox (12.5) groups than in the HFD group (30) (p = 0.0001 and =0.007, respectively). There were no differences in the DGEL between the SD and HFD+Dox groups (p = 0.42). Doxycycline administration was shown to prevent germinal epithelial loss in the testes of mice fed a high-fat diet. Future studies are necessary to evaluate the clinical usefulness of doxycycline or its analogs in persons with a habitual high-fat diet.

Research paper thumbnail of Reply to the comments of Kathpalia et al. to the article: effect of intraprostatic epinephrine on intraoperative blood loss reduction during transurethral resection of the prostate

International Urology and Nephrology, 2012

Research paper thumbnail of A dramatic case of genital radionecrosis

International Urology and Nephrology, 2009

Background Epidermoid carcinoma of the penis presents in 1% of malignant tumors in men. Penis can... more Background Epidermoid carcinoma of the penis presents in 1% of malignant tumors in men. Penis cancer treatment has traditionally been total or partial amputation. There are authors who consider radiation to be part of penis cancer treatment in select casesespecially the use of brachytherapy and external radiation. Clinical case The case of a 48-year-old male who in 2004 presented with an ulcerated lesion of the penis that was left unattended to is presented. Two years later, he sought medical attention and physical examination revealed an ulcerated penile lesion with poorly defined edges and limited to the glans. Diagnosis The lesion was biopsied and the histopathological study reported Epidermoid Carcinoma. After radiological studies, it was classified as stage T2-N0-M0. Treatment Total penectomy without lymphadenectomy was performed. The patient received adjuvant treatment of 15 sessions of cobalt radiation treatment at a dose of 3,500 cGy. Six months later, the patient noticed the presence of erythema at the genital and inguinal level which later ulcerated and extended toward the perineum. The disease progressed tragically and the patient died 2 years later.

Research paper thumbnail of Effect of intraprostatic epinephrine on intraoperative blood loss reduction during transurethral resection of the prostate

International Urology and Nephrology, 2012

Objective To determine whether the use of intraprostatic epinephrine during transurethral resecti... more Objective To determine whether the use of intraprostatic epinephrine during transurethral resection of the prostate reduces intraoperative blood loss. Methods A random, double-blind, prospective study was carried out on twenty-three patients that underwent transurethral resection of the prostate. Patients were divided into two groups: (1) group receiving intraoperative intraprostatic injection of epinephrine (thirteen patients) and (2) group receiving intraoperative intraprostatic injection of saline solution as placebo (ten patients). Blood loss was quantified with the following formula: irrigation solution hemoglobin 9 1000/intraoperative presurgical serum hemoglobin. The variables analyzed were blood loss, resection time, presurgical prostate volume, and grams of resected tissue. Students t test and Pearson correlation were used for their analysis. Results There were thirteen patients in the epinephrine group and ten patients in the placebo group. Mean blood loss in the epinephrine group was significantly lower than in the placebo group (127.48 mL ± 77.0 mL vs. 336.63 ± 185.6 mL, 95% CI, 45-234, P \ 0.001). There were no statistically significant differences in mean resected grams or mean resection time between the two groups. One patient in the epinephrine group presented with intraoperative hypertensive crisis (7.7%). Conclusions Intraprostatic epinephrine injection can be used to reduce blood loss during transurethral resection of the prostate in selected patients. Cardiovascular monitoring should be carried out during its application. Resection time and grams of resected tissue continue to be the most influential factors in relation to blood loss in patients undergoing this treatment modality.

Research paper thumbnail of Antitumor effect of meclofenamic acid on human androgen-independent prostate cancer: a preclinical evaluation

International Urology and Nephrology, 2011

Purpose Prostate cancer is a worldwide public health problem and its treatment continues to be a ... more Purpose Prostate cancer is a worldwide public health problem and its treatment continues to be a therapeutic challenge especially in patients with metastatic androgen-independent cancer. Inflammation is a process that has been involved in the origin of this cancer and its inhibition has been postulated as a prophylactic and therapeutic strategy. The present study evaluated two non-steroidal anti-inflammatory drugs (meclofenamic acid and mefenamic acid) that have been studied very little in regard to cancer treatment. Methods In vitro, the cytotoxic effects of meclofenamic acid and mefenamic acid were determined in human prostate cancer cell lines (LNCaP: androgendependent; and PC3: androgen-independent). In vivo trials were divided into two phases; meclofenamic acid toxicity was initially determined at different doses (0, 5, 10 and 20 mg/kg/day/25 days) in BALB/ c mice, after which a trial using non-toxic doses was carried out to evaluate the antitumor efficacy of the drug in a PC3/nude-mouse model of human androgen-independent prostate cancer. Results In vitro trials showed that only meclofenamic acid is highly cytotoxic in neoplastic prostate cells. The 5 and 10 mg/kg/day/25 day doses did not cause relevant toxicity in the BALB/c mouse trial, and so both doses were used in the nude-mouse model of cancer trial. This latter trial showed that meclofenamic acid significantly reduces tumor growth, prolongs survival, and is even capable of generating

Research paper thumbnail of Association between human papillomavirus in men and their sexual partners and uterine cervical intraepithelial neoplasia

International Urology and Nephrology, 2008

Objectives To determine whether the presence of human papillomavirus (HPV) in men is a risk facto... more Objectives To determine whether the presence of human papillomavirus (HPV) in men is a risk factor in the development of intraepithelial cervical neoplasia in their sexual partners and to corroborate HPV frequency and type. Materials and methods A case-control study was carried out in the city of Colima, Mexico, from

Research paper thumbnail of Metalloproteinase-1 usefulness in urethral stricture treatment

International Urology and Nephrology, 2011