Search

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10 - 8 ) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10 - 6 ). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Written informed consent was obtained from study participants or, for those with substantial cognitive impairment, a caregiver, legal guardian or other proxy. Study protocols for all cohorts were reviewed and approved by the appropriate institutional review boards., (© 2024. The Author(s).) more...

Introduction: Epidemiological data are crucial for adopting primary and secondary prevention strategies and to develop screening protocols against prostate cancer (PCa). Despite the comprehensive characterization of PCa across White and Black men, there is a lack of data from the Mexican population. This manuscript presents data from the Can.Prost registry that captures PCa trends over the past two decades in Mexico City; furthermore, we aimed to compare clinical differences and oncological outcomes before and after the promotion of early detection actions through a campaign against PCa that occurred in 2014., Methods: A retrospective observational study on newly diagnosed Mexican PCa patients was carried out at the Instituto Nacional de Cancerología (INCan) in Mexico City. During 2014 and 2015, a project for the early diagnosis of PCa ("OPUS program") was launched in the aforementioned tertiary hospital. Starting at the age of 45 years, all men were invited for a PSA measurement and a specialist urologist consultation. All individuals with clinical or biochemical suspicion of PCa (PSA > 4 ng/mL), in the context of age and prostate volume, underwent ultrasound-guided transrectal prostate biopsy. Then, patients with pathologically confirmed prostate cancer were stratified according to the year of diagnosis: Group A accounted for those diagnosed between 2000 and 2014 and Group B for those patients diagnosed in the timeframe of 2015-2021. Comparisons of PCa characteristics, treatment modalities and oncologic outcomes between Group A and B were performed., Results: Overall, we collected data from 2759 PCa patients from 2000 to 2021. The median PSA at baseline was 32 ng/mL, and 25% had a family history of PCa. Overall, 25.8% were asymptomatic and 46% had a non-metastatic presentation. After the OPUS campaign, PSA at diagnosis was significantly lower across all age groups. The incidence of PCa diagnosis in asymptomatic men was higher (31.4% vs. 19.9%) and a higher proportion of men were diagnosed with organ-confined, palpable disease (46% vs. 28%) ( p < 0.001). The rate of patients eligible for active/radical treatment was higher after the OPUS campaign (patients who received surgery increased from 12.78% to 32.41%; patients who underwent radiation increased from 28.38% to 49.61%). The proportion of patients diagnosed with non-clinically significant disease was negligible and remained stable across time., Conclusions: PCa in Mexican patients displays aggressive features at diagnosis, whereas the rate of non-significant disease is negligible. The introduction of early detection strategies may lead to lower symptomatic and metastatic PCa and higher opportunities for radical treatment. This emphasizes the need for public awareness and for adjustment of screening strategies to the peculiarities of the Mexican population. more...

Background : The lactate/pyruvate (LP) ratio has been studied as an alternative to serum lactate to determine clinical prognosis. Despite its clinical utility, there is a paucity of evidence evaluating the role of the L/P ratio in patients with sepsis. Methods : We assessed the clinical utility of the L/P ratio in patients with sepsis. The L/P ratio was measured at baseline, 4 and 8 h after admission. Our primary outcome was to determine the prognostic utility of the L/P ratio on the 15-day mortality risk. Our secondary outcomes were to compare the L/P ratio across time and its prognostic utility against standard risk calculators such as APACHE-II and SOFA scores. Results : We had a total of 80 patients, with 18 (22.5%) survivors and 62 (77.5%) non-survivors. While we found that patients having higher L/P ratios at 8 h had an increased 30-mortality risk (OR 1.08, 95% CI 1.02-1.18), the model's performance showed no difference when compared to other measurements of the L/P ratio that showed no association with mortality ( p -value: 0.45). For our secondary outcome, we found that the APACHE-II and SOFA scores have better performance and predictability than the L/P ratio (AUC 0.83 and AUC 0.80, respectively), but showed no association with mortality (OR 1.07, 95% CI 1.01-1.17 and OR 1.08, 95% CI 1.02-1.18). Conclusions : Based on our findings, the L/P ratio appears to function more effectively as an early predictor of mortality when used as an adjuvant biomarker with other clinical parameters. more...

Tumor lysis syndrome (TLS) represents an oncological emergency characterized by the rapid disintegration of neoplastic cells and subsequent release of their intracellular content into the systemic circulation due to cytotoxic therapy. However, a rare variant, spontaneous TLS (STLS), can occur without an evident precipitating factor. Prompt recognition of high-risk individuals and initiation of prophylactic interventions are crucial to forestall complications of electrolyte imbalance, such as cardiac arrhythmias or sudden death. We present the case of a 74-year-old male who was referred to the hematologist/oncologist's office after exhibiting pelvic pain, progressive weakness, fatigue, unintended weight loss over the last five months, and an imaging study revealing osteolytic lesions suggestive of a malignant condition. Initial diagnostic assessment revealed a kappa-light-restricted multiple myeloma, hypercalcemia, hyperuricemia, hyperphosphatemia, and elevated creatinine, diagnosing STLS. This case illustrates an uncommon presentation of STLS and malignant hypercalcemia in the setting of multiple myeloma. We expound upon potential tumor- and patient-specific risk factors previously documented to precipitate STLS, correlate them with our case, and provide comprehensive insights into the diagnostic, therapeutic, and noteworthy educational aspects for clinicians., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Dorsey-Trevino et al.) more...

Background: Although substance use may have adverse impacts on cancer outcomes, little is known regarding patterns of concurrent substance use with cannabis among cancer patients. Our objective was to examine predictors of concurrent substance use with cannabis among cancer patients since their cancer diagnosis and explore perceptions of cannabis among these patients., Methods: Patients treated at a National Cancer Institute-designated comprehensive cancer center were invited to participate in an electronic survey regarding medical cannabis from August to November 2021. Survey data were linked to internal data resources including electronic health records and patient intake forms to obtain history of substance use (defined as within at least 3 months of cancer diagnosis) of cigarettes, injection drugs, high levels of alcohol, or clinically unsupervised prescription drugs (total n = 1094). Concurrent substance users were defined as those with any reported substance use and cannabis use at the time of cancer diagnosis. We used descriptive statistics (χ2 or exact tests) to compare groups and estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) to identify predictors of substance use among users and nonusers of cannabis., Results: Approximately 45% (n = 489) of the sample reported cannabis use since their cancer diagnosis. Of patients who reported using cannabis, 20% self-reported concurrent polysubstance use, while 8% of cannabis nonusers reported substance use (P < .001). Among patients who use cannabis, those who reported 2 or more self-reported treatment-related symptoms (eg, pain, fatigue) were more likely to have self-reported concurrent substance use (AOR = 3.15, 95% CI = 1.07 to 9.27) compared with those without any symptoms. Among nonusers, those with lower educational background were more likely to have a history of concurrent substance use (AOR = 3.74, 95% CI = 1.57 to 8.92). Patients who use cannabis with concurrent substance use were more likely to report improved sleep (P = .04), increased appetite (P = .03), and treatment of additional medical conditions (P = .04) as perceived benefits of cannabis use., Conclusions: High symptom burden may be associated with concurrent substance use with cannabis among cancer patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.) more...

Castleman´s disease (CD) is a rare lymphoproliferative disorder. Concurrent autoimmune disease and CD are uncommon, but even more so, comorbid CD and autoimmune hemolytic anemia (AIHA). To the best of our knowledge, this case represents the first successful AIHA and multicentric CD (MCD) treatment using rituximab as first-line treatment. We present the case of a 53-year-old woman with a 10-year history of plasma cell variant CD who arrived at the emergency department with signs and symptoms of anemia. On admission, we made a preliminary diagnosis of hemolytic anemia and initiated immunosuppressive therapy with rituximab and steroids. After seven days, the patient recovered according to clinical and laboratory parameters, and we discharged her early. We portray a rare occurrence of CD and AIHA successfully treated with rituximab and steroid therapy, which makes our case unique., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Cáceres Medina et al.) more...

Single-center prospective cohort diagnostic accuracy study. Our study aimed to evaluate the accuracy and reproducibility of Thoracic Ultrasound (TUS) in detecting pulmonary pathology in immunosuppressed patients. We conducted a single-center prospective study. Consecutive patients with febrile neutropenia who underwent CT (Computerized Tomography) underwent TUS evaluation within 24h of CT. Both studies were performed by an expert who was blinded to the clinical information and results of the alternative imaging modalities. 34 patients met the inclusion criteria. The median age was 39.9 years (±17 standard deviation). TUS as a diagnostic test had a sensitivity of 92.9% and specificity of 83.3%, negative predictive value of 71.4%, and positive predictive value of 96.3%. Substantial between-method agreement was demonstrated with a kappa of 0.71 (P = .001) between the TUS and chest CT findings. We obtained a kappa of 1 (P = .001) for the final diagnosis of Pleural Effusion (PE). We concluded that TUS is a promising screening test for immunocompromised individuals. The results showed good diagnostic performance of TUS compared to CT for the detection of pulmonary findings highly suggestive of pathology with high accuracy and reproducibility., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.) more...

Background: While second-generation tyrosine kinase inhibitors (TKI) revolutionized treatment for patients with chronic myeloid leukemia (CML) who developed a suboptimal response to imatinib, many patients in developing countries are fixed to the latter due to socioeconomic barriers. Despite this scenario, scarce information is available to evaluate the clinical prognosis of these patients., Methods: We conducted a retrospective cohort analysis to compare the overall mortality of patients with CML who developed a suboptimal response to a standard dose of imatinib and were treated with either high-dose imatinib or a second-generation TKI. We created a marginal structural model with inverse probability weighting and stabilized weights. Our primary outcome was overall survival (OS) at 150 months. Our secondary outcomes were disease-free survival (DFS) at 150 months and adverse events., Results: The cohort included 148 patients, of which 32 received high-dose imatinib and 116 a second-generation TKI. No difference was found in the 150-month overall survival risk (RR: 95% CI 0.91, 0.55-1.95, P-value = .77; RD: -0.04, -0.3 to 0.21, P-value = .78) and disease-free survival (RR: 1.02, 95% CI 0.53-2.71, P-value = .96; RD: 0.01, -0.26 to 0.22, P-value = .96). There was also no difference in the incidence of adverse events in either group., Conclusion: Ideally, patients who develop a suboptimal response to imatinib should be switched to a second-generation TKI. If impossible, however, our findings suggest that patients treated with high-dose imatinib have a similar overall survival and disease-free survival prognosis to patients receiving a second-generation TKI., Competing Interests: Disclosure David Gomez-Almaguer receives compensation for national lectures from Abbvie, Bristol Myers Squibb, Janssen, AMGEN, and Roche; compensation for participation in the advisory board from Abbvie, Bristol Myers Squibb, Janssen, AMGEN, and Roche. Andres Gomez-De Leon receives compensation for national lectures from Abbvie and BMS; compensation for participation in advisory Board from Abbvie and BMS. The rest of the authors declare no competing financial interests., (Copyright © 2023 Elsevier Inc. All rights reserved.) more...

Competing Interests: Competing interests: None declared.

Autologous hematopoietic stem cell transplantation (HSCT) has been recognized as treatment alternative for patients with severe, refractory autoimmune rheumatic diseases (ARDs). Usually, anti-thymocyte globulin (ATG)-containing conditioning regimens are employed; however, ATG is unavailable in some developing nations. We report our 15-year clinical experience autografting patients with ARDs with an ATG-free conditioning regimen and a brief assessment of patient-reported outcomes post-HSCT. All patients had active disease and were resistant to multiple lines of treatment. Event-free survival (EFS) was assessed using the Kaplan-Meier method. Eight patients underwent autologous HSCT. Diagnoses included juvenile idiopathic arthritis (n = 3), systemic lupus erythematosus (n = 2), systemic sclerosis (n = 2), and rheumatoid arthritis (n = 1). Median time from diagnosis to HSCT was 3 years (0.75-19). Hematological recovery was documented in all recipients, and 4 patients (50%) completed the procedure in a completely ambulatory setting. Five (62.5%) patients achieved complete response and 3 (37.5%) partial response. The median EFS was 7 months (95% CI, 4.97-9.02), and the 1-year EFS rate was 21.9% (95% CI, 18.25-25.76). Transplant-related mortality was 0%, and 1 recipient died 8 years post-HSCT due to chronic kidney disease. Six (75%) patients presented steroid dosage reduction post-HSCT, and 2 (25%) perceived improvement in functionality despite having relapsed. HSCT is a viable treatment alternative for selected patients with severe therapy-resistant ARDs, as an improvement in disease management and quality of life was documented. The need remains to elucidate the characteristics of the optimal HSCT candidate, as well as the adequate conditioning regimen when ATG is not available. Key Points • Despite advances in the treatment of autoimmune rheumatic diseases, some patients remain refractory. In this context, autologous hematopoietic stem cell transplantation (HSCT) rises as a viable alternative. • Of 8 HSCT recipients with autoimmune rheumatic diseases, 5 (62.5%) patients achieved complete response and 3 (37.5%) partial response, with a 1-year event-free survival of 21.9%. • Transplant-related mortality was 0%, with 4 (50%) patients autografted in a completely outpatient setting. • Even when relapse presented, patients reported an improvement in functionality and quality of life; also, a better response to DMARDs and a reduction in steroid dependency post-HSCT were documented., (© 2021. International League of Associations for Rheumatology (ILAR).) more...

Background: Hematopoietic stem cell transplantation (HSCT) feasibility has increased in the last decades because of haplo-HSCT, changes in chemotherapy schedules, and the possibility of an outpatient-based HSCT. The main barriers remain in low-middle income countries. There is a lack of information regarding haplo-HSCT with a myeloablative (MAC) regimen on an outpatient basis., Objectives: Our primary objective was to determine if outpatient haplo-HSCT was feasible., Study Design: Single center, retrospective cohort, n=60 adult patients undergoing Haplo-HSCT. Descriptive statistical analysis, univariate and multivariate comparison., Patients and Method: We analyzed 60 adult patients transplanted with an intended haplo-HSCT on an outpatient basis from 2015 to 2019 in our unit. A multivariate analysis was performed on risk factors for hospitalization., Results: Median age was 27 years (15-64). All patients underwent conditioning as outpatients, and none required hospitalization before day 0. Thirteen patients (21.6%) were followed completely in the outpatient clinic and 47 (78.3%) required hospitalization in a median of 3 days after infusion (range, 1-14). The median length of stay (LOS) was 8 days (IQR, 3-17). Fever secondary to cytokine release syndrome (CRS) was the most common reason for hospitalization occurring in 43/47 (91.5%), 4 were related to infection and 36 were related to CRS. In the univariate analysis, CRS, slower engraftment, and female sex were associated with the need for hospitalization. In the multivariate analysis, only CRS remained significant (OR 9.14 [95%CI, 1.58-56.46]). The 2-year overall survival (OS) was 41.7% for ambulatory transplant vs. 38% for those requiring hospitalization (P = 0.12). The 2-year event-free survival (EFS) was 33% for outpatient patients and 16.7% for those hospitalized (log-rank, P = 0.062)., Conclusions: We demonstrated the feasibility and safety of carrying out an outpatient haplo-HSCT, potentially resulting in cost savings and perhaps a higher quality of life., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.) more...

Introduction: Thrombotic thrombocytopenic purpura (TTP) is characterized by a reduction in the von Willebrand cleavage protein ADAMTS-13, mainly as a consequence of autoimmunity. Plasma exchange (PEx) is standard, achieving complete remission (CR) in 77-83% of cases, but rates are variable depending on ADAMTS-13 activity and relapse is frequent in patients with <10%. Thus, an effective front-line immunosuppressive treatment is needed., Materials and Methods: We administered PEx daily until CR and rituximab 100 mg/dose/week for 4 consecutive weeks to 10 patients with a first TTP episode and 1 relapsed patient (8 females (72%) and 3 males (28%)). Median age was 34 years (15-46) and laboratory parameters at diagnosis were as follows: platelets 11 × 10(9)/l (range 7-27.4 × 10(9)/l), lactate dehydrogenase 1822 U/l (range 705-8220 U/l, normal 70-180 U/l), and haemoglobin 6 g/dl (range 4.2-11.8 g/dl). ADAMTS-13 activity was determined in eight patients and was <10% in all. ADAMTS-13 autoantibody titre was determined in seven patients and was >15 units/ml in all (ref: negative <12, undetermined 12-15, positive >15 units/ml); Shiga toxin was negative in all patients. The median number of PEx until CR was 7 (range 4-12); prednisone 1 mg/kg was administered to six patients., Results: The median follow-up was 22 months (range 4-49) and the estimated 2-year relapse-free survival was 89%; one HIV+ patient relapsed at 8 months follow-up. No complications related to PEx or rituximab were reported., Conclusions: Our study suggests that low-dose rituximab and PEx are effective as front-line treatment for acute TTP; however, a prospective trial is needed to demonstrate whether low-dose rituximab is as effective as the conventional dose. more...

Imatinib has been considered as the gold standard for drug therapy of chronic myelogenous leukemia (CML) because it offers higher cytogenetic response and better quality of life than traditional drugs. In this study we applied the standard 400 mg dose of imatinib in 37 CML Ph (+) Mexican patients, monitoring their cytogenetic response using fluorescent in situ hybridization and carrying out molecular analyses using reverse transcription polymerase chain reaction. The study included 19 male and 18 female patients with a median age of 41 years. The median follow-up time from diagnosis was 56 months. Thirty-six patients (97%) achieved complete hematologic response in a median time of 29 days. Complete cytogenetic response and complete molecular remission was observed in only five (13%) and three (8.1%) patients, respectively, less than the expected rate (50-90%) reported in other studies. more...

Rituximab (R) has changed the prognosis of patients with non-Hodgkin's lymphoma (NHL) in developed countries, but its role has not been analyzed in underprivileged circumstances. One hundred and two patients with NHL treated in a developing country were analyzed: 28 patients with follicular lymphoma (FL) and 74 with diffuse large B-cell lymphoma (DLCL). Patients were treated upfront with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or R-CHOP; the decision to employ R depending solely on the ability of patients to defray it. In DLCL, 42 were given CHOP and 32 R-CHOP, whereas in FL, 19 were given CHOP and 9 R-CHOP. The impact of the addition of R was found to be clearer in FL than in DLCL. In patients with DLCL, the overall survival (OS) was 87% at 80 months for those treated with R-CHOP and 84% at 145 months for those treated with CHOP (not significant). In patients with FL, the OS was 89% at 88 months for those treated with R-CHOP and 71% at 92 months for those treated with CHOP (P = 0··05). In a multivariate analysis, other variables which were identified to be associated with the OS were IPI and number of cycles in DLCL. It is concluded that R produced a mild positive impact in the OS of patients with FL, but not in those with DLCL. Since the addition of R results in a 36-fold increase in treatment costs, these observations may be important to decide therapeutic approaches in NHL patients living in underprivileged circumstances. more...

Low rates of participation constitute a serious problem for family-based drug-use prevention programs. This study analyzes the characteristics of calls for parents' participation in such programs through manipulation of the variables indicated by the Spoth and Redmond (1995) model as involved in the process (severity of the drug problem, susceptibility of the family's own children and existence of barriers to participation). Participants were 485 school pupils ages 12 to 14 years and their respective parents. Results show that the attempt to manipulate such variables did not have behavioral consequences in relation to participation in the family-based prevention program. There is a need for strategies that increase attendance of high-risk families in this type of intervention. The study's limitations are noted. more...

In two institutions in México, twelve patients were given a second allogeneic stem cell transplantation, using the "Mexican" non-myeloablative preparative regimen. Eight had a malignant condition (six acute leukemias, one myelofibrosis and one myelodysplasia), eleven individuals were allografted twice from the same donor and in one case, cells from two different umbilical cords were used. The median time to conduct the second allograft after the first one was 6 months (range 1-41). The five patients who failed to engraft after the first transplant failed also to engraft after the second one; all of them had been heavily transfused. Only three patients were successfully rescued with the second transplant, two with acute leukemia and one with aplastic anemia. Seven patients are alive 10-41 months (median 35) after the second transplant, but only three (25%) remain disease-free. The 52-month overall survival (SV) of the patients is 58%, whereas the median overall SV has not been reached, being above 52 months. Conducting a second allograft may be useful to rescue some individuals relapsing after a first hematopoietic allotransplant. more...

Cytomegalovirus (CMV)-related deaths and data of clinically evident CMV disease were assessed in a group of 47 individuals given allogeneic non-myeloablative hematopoietic stem cell transplants (NST). IgG anti-CMV antibodies were found in 56% of the donors and 76% of the receptors. Prophylactic ganciclovir was given to only 12 of the recipients during 100 days after the graft. There were no CMV-related deaths and clinically overt CMV disease was not found in any individual. The follow up post-transplant period of the patients, ranges between 30 and 810 days (median 242 days), the actuarial median survival (SV) is above 810 days and has not been reached, whereas the 810-days SV is 60%. Eighteen patients (38%) died 30-480 days after the transplant; four failed to engraft and died because of progressive disease; three died as a consequence of graft versus host disease (GVHD), whereas eleven individuals had a relapse of the malignancy and died. It is possible that the reduced bone marrow damage during NST, the prompt recovery of both the hematopoiesis and immune function in this type of allografts and the use of peripheral blood hematopoietic stem cell (HSC) is responsible for the absence of CMV-related deaths and clinical disease despite a high prevalence of CMV infection in these individuals. more...