[Ophthalmic manifestations in patients recovered from COVID-19 in Mexico]. / Manifestaciones oftálmicas en pacientes recuperados de COVID-19 en México.

Introduction and objectives: Although the ophthalmic manifestations appear to be associated with the coronavirus disease 2019 (COVID-19), there is not enough evidence. Hence, the aim of this study was to determine the various types and frequency of ophthalmic manifestations in patients recovered from SARS-CoV-2 infection in Mexico. Material and methods: This retrospective, observational and descriptive study included all patients recovered from SARS-CoV-2 infection attending the tertiary level hospital of Mexican Social Security Institute (IMSS) from June 2020 to June 2022. During the hospital admission of patients, the demographic data such age, name, gender was recorded. Ophthalmologic examination was performed under torchlight by an ophthalmologist in the Department of Ophthalmology from IMSS. Data was compiled and statistically analyzed using Fisher's exact test and Spearman correlation. Results: A total of 3,081 SARS-CoV-2-positive patients were recorded, of which 318 (10.32%) met the inclusion criteria. Of them, 21 (6.60%) had ophthalmic manifestations and the female-to-male ratio was 1.6:1. The mean age (±SD) was 47.95 ± 15.27 years and the median (interquartile range) time from the diagnosis of COVID-19, as defined by positive SARS-CoV-2 RT-PCR testing, to detection of the ophthalmic manifestation was 31 (142) days. The most common ocular manifestation was orbital mucormycosis (23.80%). Interestingly, the presence of ophthalmic manifestations was not associated with severe COVID-19 (p = 0.665). Conclusions: The ophthalmic manifestations are infrequent in patients recovered from severe COVID-19. Nevertheless, further large sample studies are needed to confirm these findings.

Ophthalmic manifestations in patients recovered from COVID-19 in Mexico.

INTRODUCTION AND OBJECTIVES: Although the ophthalmic manifestations appear to be associated with the coronavirus disease 2019 (COVID-19), there is not enough evidence. Hence, the aim of this study was to determine the various types and frequency of ophthalmic manifestations in patients recovered from SARS-CoV-2 infection in Mexico. MATERIAL AND METHODS: This retrospective, observational and descriptive study included all patients recovered from SARS-CoV-2 infection attending the tertiary level hospital of Mexican Social Security Institute (IMSS) from June 2020 to June 2022. During the hospital admission of patients, the demographic data such age, name, gender was recorded. Ophthalmologic examination was performed under torchlight by an ophthalmologist in the Department of Ophthalmology from IMSS. Data was compiled and statistically analyzed using Fisher's exact test and Spearman correlation. RESULTS: A total of 3081 SARS-CoV-2-positive patients were recorded, of which 318 (10.32%) met the inclusion criteria. Of them, 21 (6.60%) had ophthalmic manifestations and the female-to-male ratio was 1.6:1. The mean age (±SD) was 47.95±15.27 years and the median (interquartile range) time from the diagnosis of COVID-19, as defined by positive SARS-CoV-2 RT-PCR testing, to detection of the ophthalmic manifestation was 31 (142) days. The most common ocular manifestation was orbital mucormycosis (23.80%). Interestingly, the presence of ophthalmic manifestations was not associated with severe COVID-19 (p=0.665). CONCLUSIONS: The ophthalmic manifestations are infrequent in patients recovered from severe COVID-19. Nevertheless, further large sample studies are needed to confirm these findings.

Hepatocellular carcinoma in the noncirrhotic liver: Clinical features and outcomes in Veracruz, Mexico. / Carcinoma hepatocelular en hígado no cirrótico: características clínicas y resultados en Veracruz, México.

INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is the most frequent primary tumor of the liver. HCC in the noncirrhotic liver accounts for 15-20% of all HCC. Noncirrhotic HCC is a clinically different entity because of the non-neoplastic liver parenchyma involved. Our aim was to describe the presentation, treatment, and predictive survival results of noncirrhotic HCC in Veracruz. MATERIAL AND METHOD: A retrospective study, spanning 13 years, was conducted on patients with noncirrhotic HCC. It analyzed their clinical characteristics, fibrosis/cirrhosis biologic index (NAFLD, MELD, ALBI, APRI, CDS, FIB-4, GUCI, Lok) results, disease treatment, and survival. RESULTS: From a total of 168 cases of HCC, 33 (19.6%) noncirrhotic patients were included in the study. Of those patients, the mean patient age was 67.3 years (51.5% men), 9.1% had hepatitis C virus infection, and 27.3% were alcoholics. Less than 20% of the patients had biologic indexes suggestive of fibrosis/cirrhosis. Mean tumor size was 7.7cm and 42.4% of the patients had alpha-fetoprotein levels>15ng/ml. A total of 52.5% of the tumors were classified as Okuda II and 30.3% of the patients had advanced disease (the Milan criteria). Liver resection was performed on 51.5% of the patients, radiofrequency ablation on 18.2%, and transarterial chemoembolization on 9.1%. The overall 5-year survival rate was 55.4%. Liver resection resulted in the best 5-year survival rate (72.7%). Age>67 years and elevated alpha-fetoprotein levels were associated with poorer survival (P<.05, log-rank). CONCLUSIONS: The characteristics and survival rate of HCC in the noncirrhotic liver were similar to those reported in other studies. Liver resection provided the highest survival rates. The liver fibrosis biologic indexes were not risk factors for survival.

Correlation between preoperative serum alpha-fetoprotein levels and survival with respect to the surgical treatment of hepatocellular carcinoma at a tertiary care hospital in Veracruz, Mexico. / Correlación de los niveles de alfafetoproteína sérica preoperatoria y sobrevida en el tratamiento quirúrgico del hepatocarcinoma en una unidad médica de alta especialidad en Veracruz, México.

INTRODUCTION: Preoperative serum alpha-fetoprotein levels can have predictive value for hepatocellular carcinoma survival. AIM: Our aim was to analyze the correlation between preoperative serum alpha-fetoprotein levels and survival, following the surgical treatment of hepatocellular carcinoma. METHODS: Nineteen patients were prospectively followed (07/2005-01/2016). An ROC curve was created to determine the sensitivity and specificity of alpha-fetoprotein in relation to survival (Kaplan-Meier). RESULTS: Of the 19 patients evaluated, 57.9% were men. The mean patient age was 68.1 ± 8.5 years and survival at 1, 3, and 5 years was 89.4, 55.9, and 55.9%. The alpha-fetoprotein cutoff point was 15.1 ng/ml (sensitivity 100%, specificity 99.23%). Preoperative alpha-fetoprotein levels below 15.1, 200, 400, and 463 ng/ml correlated with better 1 and 5-year survival rates than levels above 15.1, 200, 400, and 463 ng/ml (P<.05). CONCLUSIONS: Elevated preoperative serum alpha-fetoprotein levels have predictive value for hepatocellular carcinoma survival.

Liver resection morbidity, mortality, and risk factors at the departments of hepatobiliary surgery in Veracruz, Mexico. / Morbilidad, mortalidad y factores de riesgo de la cirugía hepática en los departamentos de cirugía hepatobiliar de Veracruz, México.

INTRODUCTION: Liver resection has been associated with high morbidity and mortality, and the most serious complication is liver failure. Patient evaluation is limited to risk scales. The 50-50 criteria and bilirubin peak>7mg/dl have been used as mortality predictors. AIM: The aim of this study was to determine the risk factors associated with morbidity and mortality for liver resection in our population. MATERIAL AND METHODS: A retrospective study was carried out on 51 patients that underwent liver resection. Sociodemographic variables, pathology, and the surgical act were analyzed, together with morbidity and mortality and their associated factors. RESULTS: Fifty-one patients, 23 men and 28 women, were analyzed. They had a mean age of 51.4±19.13 years, 64.7% had concomitant disease, and their mean MELD score was 7.49±1.79. The mean size of the resected lesions was 7.34±3.47cm, 51% were malignant, and 34 minor resections were performed. The Pringle maneuver was used in 64.7% of the cases and the mean blood loss was 1,090±121.76ml. Morbidity of 25.5% was associated with viral hepatitis infection, greater blood loss, transfusion requirement, the Pringle maneuver, lower hemoglobin and PTT values, and higher MELD, INR, bilirubin, and glucose values. A total 3.9% mortality was associated with hyperbilirubinemia, hyperglycemia, and greater blood loss and transfusions. CONCLUSIONS: The main risk factors associated with the morbidity and mortality of liver resection in our population were those related to the preoperative biochemical parameters of the patient and the factors that occurred during the surgical act.

Thymoglobulin Induction Therapy in Deceased Donor Kidney Transplantation: Single-Center Experience in Mexico.

BACKGROUND: Induction therapy is used to reduce the incidence of graft rejection and delayed graft function. Thymoglobulin is the most used inductor agent in deceased donor kidney transplantation due to its lower rejection and delayed graft function rates. METHODS: Retrospective study of patients who underwent deceased donor kidney transplantation from 2011 to 2014. Efficacy and safety outcomes evaluated were primary graft nonfunction, delayed graft function, acute rejection episodes, the lowest leukocyte count during the induction, adverse effects, eGFR, and patient and graft survival. P < .05 was considered statistically significant. RESULTS: A total of 42 patients were registered. Of these, 51.7% were female, with a mean age of 36.4 ± 11.1 years. Mean dialysis time was 112.4 ± 365 months. Mean donor age was 33.7 ± 13.1 years. Of the registered patients, 14.3% were extended criteria donors and 23.8% high-risk. Mean thymoglobulin dose was 4.4 ± 0.8 mg/kg. Primary graft nonfunction was 2.4%. Nineteen percent presented with delayed graft function and 19% with acute rejection. Mean lowest leukocyte count was of 4.6 ± 1.5 × 10(3) cells/mm(3). Mean hospital stay was 11.3 ± 6.3 days. Adverse effects were seen in 59.5% of registered patients, whereas graft survival 1 year and 3 years after transplantation was 85.3% and 56.9%, respectively. Patient survival 1 year and 3 years after transplantation was 85.3% and 53.8%, respectively. Patients who received a higher dose (>4.4 mg/kg) had a shorter hospital stay (9.4 ± 4.6 and 8.1 ± 2.3) than those who received lower dose (13.6 ± 7.9 and 12.8 ± 7.4; P < .05). CONCLUSION: Thymoglobulin induction at doses near 5 mg/kg in deceased donor kidney transplant is efficient and secure at our center.

Induction Immunosuppressive Therapy Use in Deceased Donor Kidney Transplantation: 11-Year Experience in Veracruz, Mexico.

BACKGROUND: Induction therapy reduces the frequency of acute rejection and delayed graft function in renal transplantation. Basiliximab and Thymoglobulin are most commonly used agents for induction. METHODS: A retrospective study of two transplant centers in Veracruz, Mexico compared induction therapy in deceased donor renal transplantation from 2003 to 2014. Efficacy and safety outcomes evaluated were primary graft nonfunction, delayed graft function, acute rejection episodes and hospitalizations during first year, and patient and graft survival. P < .05 was considered statistically significant. RESULTS: Seventy deceased kidney donors (40 male) were studied. Mean donor age was 32.9 ± 14.3 years, mean donor BMI 25.6 ± 4.3 kg/m(2), and mean donor creatinine 1.13 ± 0.58 mg/dL. Main cause of death was trauma (62.9%). In total, 125 kidney transplantations were performed, with female predominance (53.6%) and mean age 33.8 ± 11.8 years. Of these, 66.4% used basiliximab and 33.6% Thymoglobulin. Thymoglobulin patients were significantly older, with lower weight and BMI, and were on dialysis longer than basiliximab patients. DGF was present in 19.3% of basiliximab patients vs 16.7% in Thymoglobulin patients, acute rejection occurred in 16.9% of basiliximab patients vs 19% Thymoglobulin patients. A total of 33.7% basiliximab patients were hospitalized during the first year vs 47.6% Thymoglobulin-induced patients (P > .05). Mean graft survival was 84.2 ± 5.3 months (73.8-94.7) basiliximab vs 32.4 ± 28.7 months (28.7-36.1) Thymoglobulin, Kaplan-Meier survival did not show statistically significant differences between groups (P = .276; CI 95%). CONCLUSION: Similar transplant outcomes were obtained using basiliximab or Thymoglobulin induction in our population.

The Cost of Gastrointestinal Adverse Events and the Impact of Dose-Reductions/Discontinuations on Acute Rejection in Kidney Transplant Patients of Mycophenolate Mofetil-Related Compared to Enteric-Coated Mycophenolate Sodium: A Pharmacoeconomic Study.

BACKGROUND: Mycophenolate mofetil (MMF) is effective in decreasing rejection and graft loss in renal transplant patients. Enteric-coated mycophenolate sodium (EC-MPS) was designed to reduce MMF gastrointestinal (GI) effects. Dose manipulations in MMF/EC-MPS produce GI tolerability, increasing the risk of rejection. Significant differences in tolerance of MMF/EC-MPS may have economic influence in transplant efficacy outcomes. Herein, we performed a pharmacoeconomic evaluation of acute rejection incidence and interventions in GI-intolerant patients using MMF/EC-MPS. METHODS: A cost-effectiveness analysis was performed through a decision tree model with a 1-year time horizon estimating costs and effectiveness of MMF and EC-MPS in renal transplant patients with GI intolerance. The costs and use of resources (US dollars; USD) were from payer perspective (Mexican Social Security). Primary health outcomes were mean cost of acute rejection and GI adverse events treatment. A probabilistic sensitivity analysis (PSA) was generated to test robustness of the model. RESULTS: Calculated incidence of MMF GI intolerance was 44%, and calculated rejection incidence for MMF was 24.05%. Calculated incidence of EC-MPS GI intolerance was 29%, and calculated rejection incidence for EC-MPS was 20.1% Total cost of MMF with GI intolerance during 1-year period plus cost of treating one rejection sums $752,107.25 USD. Total cost of EC-MPS with GI intolerance plus cost of treating one rejection sums $638,018.97 USD. CONCLUSION: EC-MPS-based treatment is a cost-saving alternative vs MMF in GI-intolerant kidney transplant patients. PSA supports the decision to utilize EC-MPS based on cost-effectiveness analysis.

[Presentation, staging, and outcome of patients with hepatocellular carcinoma at a center in Veracruz, Mexico]. / Presentación, clasificación y evolución de los pacientes con carcinoma hepatocelular en un centro de Veracruz, México.

BACKGROUND: Hepatocellular carcinoma (HCC) staging provides a basis for calculating disease prognosis and therapeutic guidance. Liver resection and transplantation are curative options, and ablation therapies are applied to patients that are not candidates for curative treatment. Survival after liver resection or ablation therapies varies. AIMS: To describe the presentation, staging, management, and outcome in patients with HCC in our center. PATIENTS AND METHODS: Forty-two patients had a 7-year prospective follow-up. Survival was calculated with the Kaplan-Meier analysis and the log-rank test was used for its comparison between the staging systems (Okuda, BCLC, and CLIP) and types of treatment (liver resection, radiofrequency ablation, and no surgical treatment). RESULTS: The mean age of the patients was 68.9 ± 9.5 years; 57% were women. A total of 54% of the patients presented with cirrhosis and 31% were infected with hepatitis C virus (HCV). The mean tumor size was 6.48 ± 2.52cm. The CLIP 0, Okuda I, and BCLC A stages had better survival rates than the other stages (P<0.05). Survival with resection was superior (median of 32 months and survival at 1, 3, and 5 years of 83, 39, and 19.7%, respectively) to that of both radiofrequency ablation (median of 25 months and survival at 1 and 3 years of 90 and 17.2%, respectively) and no surgical treatment (1 year < 5%) (P<0.05). CONCLUSION: The patients at our center were diagnosed at late stages of HCC, as is the case in other Mexican populations. Outcome in relation to CLIP and BCLC was similar to the prognoses reported in the literature. The best results were observed in the patients with early stage disease and those that underwent HCC resection surgery.

Rejection is a strong graft survival predictor in live donor pediatric renal transplantation using cyclosporine, mycophenolate mofetil, and steroids: 5-year outcomes in a single Mexican center.

Long-term graft function and survival are of particular importance in children assuming that they have a longer transplantation life span than most adults. Because acute rejection episodes (ARE) continue to have a serious impact on graft loss, we analyzed the effects of ARE on 5-year survival and function in our population. Fifty-seven living donor kidney transplant recipients (34 males) younger than 18 years of age (13.5 ± 2.6 years; range, 5-17) were follow up for at feast 12 months using cyclosporine, mycophenolate mofetil, and steroid therapy with or without induction treatment between February 2003 and December 2010. ARE incidence during the first 12 months following transplantation was 14%. One-, 3- and 5-year serum creatinine values were 1.24 ± 0.39, 2.16 ± 2.39, and 1.76 ± 0.9 mg/dL, respectively. Mean calculated creatinine clearances (Schwartz) at 1, 3, and 5 years were 82.5 ± 24.8, 64.7 ± 24.1, and 67 ± 27.5 mL/min*1.73 m(2), respectively. Patient/graft survival rates were 96/85%, 90/72%, and 88/65% at 1, 3, and 5 years, respectively. Patients who experienced an ARE within 12 months following transplantation displayed a reduced 5-year graft survival rate (37.5%) versus those who did not (78%; P = .005). Patients who did not have an ARE during 60 months had a higher graft survival rate (76%) than those who had ARE (33%; P = .001). Patient without basiliximab induction showed a lower 5-year graft survival rate (61% vs 100%; P = not significant [NS]). ARE is an important risk factor for graft loss in the pediatric kidney transplant population.

Individualizing early use of sirolimus in renal transplantation.

One of the main goals in the current care of kidney transplant recipients is to extend long-term graft survival. Efficacious immunosuppressive agents devoid of nephrotoxicity are needed. In human clinical transplantation, sirolimus combined with other immunosuppressive drugs has proven to be a powerful immunosuppressant capable of preventing acute graft rejection, as well as of improving renal function, renal histology, and graft survival when compared with immunosuppressive regimens that include calcineurin inhibitors. The valuable experience gained through many clinical studies allows clinicians to plan sirolimus use. We present a review of the clinical experience and literature review on the use of sirolimus in the first 12 months posttransplantation.

Successful renal transplantation from a deceased donor with pesticide intoxication: a case report.

The number of individuals awaiting organ transplantation exceeds the number of organs. Patients who die from intoxication are rarely accepted as potential organ donors. Herein we have presented the results of kidney transplantations performed from a deceased 20-year-old female donor with suicidal ingestion of a pesticide (carbamate). The procured kidneys were successfully transplanted. Patients and grafts are doing well at 4 months following transplantation. There are few reports of successful transplantation of organs obtained from patients who die from various intoxications. Poisoned patients represent another pool of organ donors for transplantation services.

Neutrophil depletion and chemokine response after liver ischemia and reperfusion.

Neutrophils play a major role in the hepatic microvasculature following liver ischemia and reperfusion (I/R). Leukocyte cytokine chemoattractants (chemokines) are produced by neutrophils and cause neutrophil activation in I/R injury. We examined the role of neutrophils in the production of chemokines in the liver and lung inflammatory response following liver I/R. C57BL/6 mice were subjected to partial liver ischemia for 90 min. Four groups of animals were included: sham group, sham group with neutrophil depletion, ischemic control group, and ischemic control with neutrophil depletion. We evaluated at 3 h liver injury measurements, serum macrophage inflammatory protein-2 (MIP-2) and macrophage inflammatory protein-1 alpha (MIP-1alpha) chemokines, liver and lung tissue myeloperoxidase (MPO), and liver and lung histology. Statistical analysis included analysis of variance (ANOVA), and Student-Newman-Keuls and Kruskal-Wallis multiple comparison Z-value tests. Ischemic controls showed a significant increase in liver enzyme levels along with statistically significant higher liver and lung MPO activity values than the rest of the other groups (p < .05). MIP-2 values were higher in the ischemic control group when compared to the ischemic neutrophil depleted group. MIP-1alpha levels showed opposite results, being significantly lower (p < .05) in the ischemic control as compared to the neutrophil-depleted group. Improved liver and lung histopathological features were observed in the ischemic neutrophil depleted group when compared to the ischemic control group. Our study confirmed the key role of neutrophils in liver I/R injury and appeared to suggest some relationship between neutrophils and the production of certain chemokines, such as MIP-1alpha, which had an inverse relationship in the absence of neutrophils. Further studies will confirm the validity of these preliminary observations.

L-selectin blockade and liver function in rats after uncontrolled hemorrhagic shock.

Hemorrhagic shock (HS) and resuscitation can be seen as a global body ischemia-reperfusion (I/R) injury characterized by neutrophil infiltration and organ damage. Liver dysfunction occurs early after HS. Adhesion molecules are needed for the first steps ofneutrophil migration. Thus, the purpose of this study was to investigate the role of L-selectin in the liver after uncontrolled HS and resuscitation. Forty-eight Sprague Dawley rats were subjected to uncontrolled HS and resuscitation. Animals were divided into three groups: sham, uncontrolled HS and resuscitation, and uncontrolled HS and resuscitation with anti-L-selectin treatment. At 6 we evaluated liver injury tests, liver tissue myeloperoxidase (MPO), and liver histology. Survival was followed for 3 days and compared between groups. Statistical analysis included Fisher's exact test and one-way analysis of variance. Survival significantly increased from 30% in the control group to 60% in the treated group (p < .05). Hepatocellular and structural injury as well as neutrophil infiltration was significantly decreased in treated animals (p < .05). Thus, blockade of L-selectin resulted in decreased hepatocellular injury and increased survival in our model of uncontrolled HS. Selectins may be important therapeutic targets for blockade in the treatment of HS.

Nitric oxide diminishes apoptosis and p53 gene expression after renal ischemia and reperfusion injury.

BACKGROUND: The role of nitric oxide in the ischemic injury of the kidney is still controversial. The aim of this study was to reevaluate the beneficial effect of exogenous nitric oxide and define its effects as regulator of gene p53 expression and apoptosis in the ischemic renal injury. METHODS: Sprague-Dawley rats were subjected to 75 min of renal warm ischemia and contralateral nephrectomy. The animals were divided into six groups (n=6 per group): Two sham groups at 4 and 24 hr, two ischemic control (IC) at same times and two treated groups (Na-NP), studied at same intervals, where sodium nitroprusside (5 mg/kg) was given 15 min before reperfusion. The parameters evaluated included: serum creatinine, blood urea nitrogen, neutrophil infiltration determined by myeloperoxidase, gene p53 expression determined by reverse transcriptase polymerase chain reaction, apoptosis determined by peroxidase in situ technique and light histology. RESULTS: There were significant improvements in serum creatinine and blood urea nitrogen at 24 hr in the NA-NP group when compared with the IC group (P<0.05). Myeloperoxidase levels were higher in the IC when evaluated against the Na-NP groups. Na-NP exhibited a downregulating effect in the expression of gene p53 when compared to the IC group. Apoptosis was more evident in the IC group and had moderately increased histological damage when compared to the Na-NP group. CONCLUSIONS: Nitric oxide demonstrated a protective effect in the ischemic injury of the kidney and exerted an antiapoptotic action dowregulating the expression of gene p53.

P-selectin and chemokine response after liver ischemia and reperfusion.

BACKGROUND: P-selectin plays a major role in the earliest phase of polymorphonuclear neutrophil recruitment in the hepatic microvasculature after liver ischemia and reperfusion. Leukocyte cytokine chemoattractants (chemokines) cause polymorphonuclear neutrophil activation in ischemia and reperfusion injury. In this study, we examined the role of P-selectin in the production of chemokines in the liver and lung inflammatory response after 90 minutes of warm ischemia. STUDY DESIGN: Thirty-six C57BL/6 mice were subjected to partial liver ischemia for 90 minutes. Three groups of animals were included (n = 12 per group): the sham group, the ischemic control group, and the P-selectin-deficient gene targeted mice group. After 3 hours, we evaluated liver injury measurements, serum chemokines (MIP[macrophage inflammatory protein]-1alpha and MIP-2), liver and lung tissue myeloperoxidase, and liver and lung histology. Statistical analysis included ANOVA, Student-Newman-Keuls', and Kruskal-Wallis Multiple Comparison Z-value tests. RESULTS: P-selectin-deficient mice showed significant decreases in liver enzyme levels (p < 0.05) and marked decreases in serum MIP-1alpha and MIP-2 chemokine determinations (p < 0.05) when compared with ischemic controls. Neutrophil infiltration was significantly ameliorated in the liver (p < 0.05) and markedly decreased in the lung, as reflected by decreased MPO levels. Improved histopathologic features in the liver and lung were observed in the P-selectin-deficient mice group compared with ischemic controls. CONCLUSIONS: Our study confirms the key role of P-selectin in the pathogenesis of liver ischemia and reperfusion and the production of chemokines. P-selectin-deficient animals had improved liver function, decreased neutrophil infiltration, and decreased MIP- 1alpha and MIP-2 responses.