Investigación Clínica

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Recognitions and achievements in our 65th Anniversary

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Investigacion Clinica celebrated its 65th anniversary in 2025 with a busy publishing sea- son. We received over 150 submissions; of these, 120 were reviewed by the Editorial Commit- tee, which welcomed two new members: José Luis Arcaya (Neuroscience) and Nereida Valero- Cedeño (Virology). We published four editorials and 35 articles: 28 original articles, 6 reviews, and 1 case report. Thirty-one percent of these originated in Venezuela, while 69% came from other countries, including Brazil, Spain, and China. We had 58 reviewers: 64% were Venezu- elan, and 36% were from other countries. Notably, most international reviewers graduated from Venezuelan universities but work abroad. We are deeply grateful to them for maintaining their connection to their homeland. We remain included in international indexes such as Scopus and Web of Science, and we are the Venezuelan medical journal with the most issues indexed by SciELO-Venezuela. CrossRef reported that published works are requested 2,000-4,000 times per month. In this first issue of 2026, we have updated the Instructions for Authors to better meet the ongoing demands of scientific communication and to prevent incidents that have oc- curred in recent years. Specifically, proposals for articles must be the sole responsibility of the authors, through the corresponding author, because some submissions from promoters or edi- torial assistants raised serious doubts about the work’s suitability, compromising the journal’s quality and, on some occasions, prompting us to consider retracting the manuscript. Unfortu- nately, 2026 brought us the sad news of the passing of our editor from 1972 to 1990, virologist Dr. Slavia Ryder, who died on January 20th. This issue includes an In Memoriam written by one of her first students, Dr. José Esparza.

IN MEMORIAM. Dra. Slavia Cristina Ryder Jaksic (1938-2026)

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Born in Maracaibo on June 16, 1938, Slavia Cristina Ryder Jaksic dedicated her life to science, the University of Zulia, and serving Venezuelan public health. From a young age, she showed a strong calling for the natural sciences, which led her to study medicine at the University of Zulia, where she graduated with honors in 1962. During her studies, under the guidance of Dr. Américo Negrette, she became involved in the emerging scientific research activity that led to the creation of the Instituto de Investigaciones Clínicas at the Facultad de Medicina de LUZ. She specialized in virology and arboviruses, focusing especially on Venezuelan Equine Encephalitis (VEE), a disease she dedicated more than 30 years of continuous work to, combining laboratory research, field studies, and epidemiological surveillance in Zulia state.

Effects of Vitamin D deficiency and supplementation on 25(OH)D3 levels and neuropsychobehavioral development in premature infants.

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This study systematically examined how vitamin D metabolic imbalance impacts 25(OH)D3 levels and neuropsychological development in premature infants and proposed a personalized supplementation approach. Premature infants were classified as adequate, insufficient, or deficient based on umbilical cord blood 25(OH)D3 levels and then randomly assigned to either a standard-dose group (800 IU/d) or an individualized supplementation group (400-1000 IU/d) with vitamin D. In the vitamin D-deficient group, infants receiving personalized supplementation had significantly higher 25(OH)D3 levels at three and nine months, adjusted for gestational age, than those receiving the fixed dose, indicating that 1000 IU/d is more effective than 800 IU/d for correcting deficiency (p<0.05). At nine and 18 months adjusted gestational age, infants in the vitamin D-insufficient and deficient groups scored significantly lower on the Gesell Developmental Scales across categories such as gross motor, fine motor, language, adaptive, and social skills compared to the adequate group (p<0.05). Within the deficient group, those receiving personalized supplementation scored higher in all five areas at both nine and 18 months adjusted gestational age compared to those on the fixed dose (p<0.05). The study highlights notable differences in umbilical cord blood 25(OH)D3 levels among premature infants, emphasizing that a customized vitamin D supplement protocol is more effective for correcting deficiencies.

The impact of complement C1q/tumor necrosis factor-related protein 6-mediated cardiomyocyte pyroptosis on myocardial fibrosis in rats with myocardial infarction.

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Complement C1q/tumor necrosis factor-related protein 6 (CTRP6) has anti-inflammatory and metabolic regulatory properties, but its role in ameliorating post-myocardial infarction (MI) myocardial fibrosis via pyroptosis inhibition is unclear. This study investigated whether CTRP6 im- proves post-MI myocardial fibrosis and cardiac dysfunction by suppressing car- diomyocyte pyroptosis through the NLRP3/caspase-1/GSDMD pathway. Thirty Sprague-Dawley rats were randomized to sham-operated (Sham), MI model (MI), or CTRP6-treated (MI+CTRP6) groups. MI was induced by left anterior descending coronary artery ligation; MI+CTRP6 rats received daily subcutane- ous recombinant CTRP6 (0.2 mg/kg) from day 3 post-surgery for 28 days. Car- diac function, fibrosis markers, pyroptosis-related proteins, and inflammatory cytokines were assessed via Western blot, Masson staining, and ELISA. CTRP6 expression was lower in MI vs. Sham (p<0.05). CTRP6 treatment restored its expression, reduced fibrosis markers and collagen deposition, and improved cardiac function (p<0.05). It also downregulated pro-inflammatory cytokines and increased anti-inflammatory cytokines (p<0.05). In other words, exoge- nous CTRP6 ameliorated fibrosis and cardiac function by directly inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway.

Assessment of the efficacy of tamsulosin and potassium citrate in promoting spontaneous ureteral stone expulsion.

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This study aimed to evaluate the effectiveness of tamsulosin combined with potassium citrate in promoting the spontaneous passage of ureteral stones ≤10 mm. A retrospective analysis was performed on 100 patients admitted between January 2020 and December 2023. Patients were divided into four groups: tamsulosin (0.4 mg/day), potassium citrate (3 g/day), combined treatment (tamsulosin + potassium citrate), and a control group (analgesics only+ regular water intake). Primary outcomes assessed over four weeks included stone passage rate, passage time, stone location and composition, and safety. Secondary outcomes covered pain control, imaging and laboratory indicators, and quality of life. Baseline characteristics were comparable across groups. The combined treatment group showed the highest stone expulsion rate, which was significantly higher than that of the tamsulosin, potassium citrate, and control groups (p<0.05). The median stone expulsion time was also shortest in the combined group (p<0.05). Expulsion rates for lower ureteral stones, uric acid stones, and calcium stones were significantly higher in the combined group (p<0.05), while the rate for upper stones was not statistically significant (p>0.05). No serious adverse events occurred, and safety profiles were similar across all groups. Secondary outcomes, including pain control and quality of life, showed significant improvements in the combined group compared with the other groups (p<0.05). The combination of tamsulosin and potassium citrate significantly increases the rate and shortens the time of spontaneous ureteral stone expulsion, with good safety and improved quality of life, supporting its role in medical expulsive therapy.

Factores de virulencia y su efecto sobre la sensibilidad a los fármacos antifúngicos de Candida albicans causante de vulvovaginitis candidiásica recurrente.

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Candidal vulvovaginitis (CVV) is mainly caused by Candida albicans. The activities of phospholipases, proteases, hemolysins, and biofilms were evaluated as virulence factors in C. albicans causing recurrent CVV, and their effects on antifungal susceptibility were assessed to understand their influence on antifungal sensitivity. A total of 22 C. albicans strains isolated from patients with recurrent CVV who attended the Microbiology Department of the La Floresta Medical Institute, Caracas–Venezuela, from July 2023 to June 2024 were analyzed. Phospholipase, protease, and hemolysin activity, along with biofilm formation and the minimum inhibitory concentration (MIC) susceptibility profiles for fluconazole, voriconazole, and amphotericin B, were determined using the Vitek 2 Compact® assay with the AST-YSO1® card. All strains produced hemolysins; 77% exhibited phospholipase activity, and 27.3% expressed prote- ases. 82% were capable of forming biofilms. Resistance rates were 82% for flu- conazole and 73% for voriconazole; all strains were susceptible to amphotericin

There was no statistically significant relationship between the three drugs tested and the virulence factors studied. Virulence factors are independent vari- ables in the antifungal susceptibility profile but participate in different stages of infection and are associated with the clinical presentation of CVV.

Study on the predictive model of response of patients with inflammatory bowel disease to infliximab treatment.

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This study aimed to develop a predictive model for how patients with inflammatory bowel disease (IBD) respond to infliximab (IFX) treatment. One hundred adult IBD patients admitted to Shulan (Hangzhou) Hospital from August 2023 to November 2024 were included and divided into response and non- response groups based on their reaction to IFX. The response group consisted of 57 patients (57.0%), while the non-response group had 43 patients (43.0%). Clinical data, including gender, age, BMI, disease type (Crohn’s disease/ulcer- ative colitis), disease activity indices (CDAI/UCAI), history of IFX treatment, and infusion reactions, were collected and compared between the two groups. Additionally, biomarker levels, such as TNF-α, CRP, calprotectin, anti-infliximab antibody (ATI), IL -6, and IL -8, were measured during the midcourse of IFX treatment. Single-factor analysis identified variables that differed, and logistic regression showed that calprotectin level (OR=1.099, 95%CI=1.039-1.163), ATI (OR=3.756, 95%CI=1.222-11.546), IL -6 (OR=1.261, 95%CI=1.069-1.488), and IL -8 (OR=1.014, 95%CI=1.004-1.024) were key factors influenc- ing treatment response (p < 0.05). A nomogram was created using these fac- tors to predict treatment response in IBD patients. ROC analysis showed AUC values of 0.809, 0.762, 0.850, and 0.775 for calprotectin, ATI, IL -6, and IL - 8, respectively, with corresponding 95% confidence intervals. The calibration curve indicated good model fit. These findings underscore the important roles of these cytokines in IBD pathogenesis and the action of IFX, as well as the high predictive power of the nomogram model.

Withaferin-A induces apoptosis and autophagy in colorectal cancer cell lines via down-regulated expression of histone deacetylase 1.

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Colorectal cancer (CRC) remains the third most common malignancy worldwide, and there is an urgent need for low-toxicity, mechanism-based preventives or adjuvants. Withaferin-A (WA), a plant-derived steroidal lactone, exhibits broad antitumor activity; however, its role in CRC and its interactions with epigenetic regulators, such as histone deacetylase 1 (HDAC1), remain unclear. Therefore, we investigated whether WA suppresses CRC growth by down- regulating HDAC1 while inducing apoptosis and autophagy. Caco2 and HT-29 cells were treated with 0–5 µM WA; viability, colony formation, and migration decreased significantly (IC₅₀ 0.70–1.52 µM). Techniques such as Annexin-V/7-AAD flow cytometry, MDC staining, TEM, and LC3B immunofluorescence showed that 1 µM WA notably increased apoptosis and autophagic flux, along with reduced HDAC1 and p62 levels, higher LC3B-II/I ratios, and an increased Bax/Bcl-2 ratio. Overexpression of HDAC1 via a lentiviral vector reversed these effects, confirming dependence on HDAC1. For translational relevance, eight-week-old C57BL/6J mice were first exposed to the food-borne carcinogen IQ (2-amino-3-methyl-3H- imidazo[4,5-f]quinoline, 100 mg/kg) every other day for three weeks to induce aberrant crypt foci (ACF). Starting the day after the first IQ dose, animals received WA (2 mg/kg) or vehicle (corn oil) by gavage every other day for the same period. WA reduced the number of macroscopic ACF by more than 60%, restored HDAC1-related LC3B and p62 expression to normal levels, and showed no toxicity based on body weight or general health assessments. These findings suggest that WA provides potent, low-toxicity chemopreventive effects against CRC lesion formation through HDAC1-dependent induction of apoptosis and autophagy, sup- porting its further consideration as a preventive or adjuvant agent.

Phyllanthin identified from Phyllanthus amarus attenuates arsenite-induced liver and kidney damage: Role of NF-kB pathway inhibition.

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Sodium arsenite is a common and highly toxic inorganic arse- nic compound that causes liver and kidney damage. Phyllanthus amarus is well known for its protective effects on these organs. This study aimed to identify the active phytoconstituents of the methanolic extract of P. amarus (PAME) and to explore their effects on arsenite-induced liver and kidney toxicity in experi- mental rats. The standardization of P. amarus extract was performed using high- performance liquid chromatography (HPLC). Male Wistar rats developed liver and kidney toxicity after daily oral administration of sodium arsenite (5 mg/ kg) for 4 weeks. The rats were simultaneously given coenzyme Q10 (CoQ10; 10 mg/kg) or PAME (50, 100, and 200 mg/kg). Results showed that HPLC analy- sis detected phyllanthin at a retention time of 25.41 minutes with an area of 71.84%. Arsenite treatment caused a significant (p<0.001) increase in hepatic enzymes (ALT, AST, and ALP), renal markers (BUN, uric acid, and creatinine), and direct and total bilirubin in the serum. It also significantly increased hepatic and renal levels of malondialdehyde, nitric oxide, NF-κB p65, interleukins (ILs), and TNF-α (p<0.001), while decreasing hepatic antioxidant enzymes (GSH and SOD) and overall hepatic antioxidant capacity. Notably, P. amarus extract (200 mg/kg) markedly (p<0.001) mitigated arsenite-induced changes in these serum markers, oxidative stress indicators, NF-kB p65, and inflammatory cytokines. It also improved the structure of liver and kidney tissues, maintained cellular ar- chitecture, and reduced necrosis and inflammation. In conclusion, these results suggest that phyllanthin from P. amarus protects against arsenite-induced liver and kidney damage by inhibiting NF-κB activation, reducing inflammatory cyto- kine release, and decreasing oxidative and nitrosative stress, thereby enhancing overall antioxidant capacity. Therefore, P. amarus extract may be a promising treatment for pesticide-related liver and kidney injuries in rats.

Treatment strategies and mortality risk factors in patients with multidrug-resistant Acinetobacter baumannii pneumonia: A retrospective analysis.

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This study aimed to investigate the determinants of drug resis- tance risk factors, 30-day all-cause mortality risk factors, and related clinical treatment strategies in patients with multidrug-resistant Acinetobacter bauman- nii (MDRAB) pneumonia. This retrospective study analyzed data from 168 pa- tients with MDRAB pneumonia and 141 patients with non-MDRAB pneumonia between February 2022 and February 2025. On the second day of admission, the severity of illness and use of carbapenems, tigecycline, etc., were higher in MDR- AB pneumonia patients than in non-MDRAB pneumonia patients (p<0.05). The risk factors significantly associated with MDRAB pneumonia included ICU stay prior to AB infection (p<0.001), APACHE II score ≥ 18 (p=0.002), invasive pro- cedures (p<0.001), septic shock (p=0.002), and drug abuse (p<0.001). Length of ICU stay before culture, recent surgery, APACHE II score ≥18, tigecycline- containing treatment, and the use of two or more antibiotic types (all p<0.05) were significantly linked to 30-day mortality. In a cohort of 168 MDRAB patients, the non-tigecycline treatment group (n=85) showed a significantly lower 30-day mortality rate compared to the tigecycline treatment group (n=83) (p=0.003). Among those receiving tigecycline, the incidence of gastrointestinal adverse re- actions was significantly higher, while allergic reactions were less frequent (both p<0.05). In conclusion, prior ICU admission, invasive procedures, and drug abuse are risk factors for developing MDRAB. Severe pneumonia and tigecycline treatment are strongly associated with higher mortality in MDRAB patients, and tigecycline should be used cautiously.

Ameliorative potential of astaxanthin in isoproterenol-induced heart failure in rats via the regulation of the renin-angiotensin system.

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Heart failure (HF) is a condition in which the heart cannot pump blood effectively to the body. Isoproterenol (ISO) induces HF in rodents by affecting the renin-angiotensin system (RAS). Astaxanthin (AST) is known to have protective effects on the cardiovascular system. However, clear evidence showing that AST improves HF through RAS regulation has not yet been report- ed. This study aimed to investigate the role of AST in ISO-induced HF in rats. HF was induced by intraperitoneal (i.p.) injection of ISO (5 mg/kg/day) for seven consecutive days. AST (25 and 50 mg/kg), aliskiren (30 mg/kg), ramipril (4 mg/kg), and telmisartan (8 mg/kg) were administered orally for 21 days, starting from the last dose of ISO (day 8). Changes in systolic and diastolic blood pressure and heart rate associated with HF were measured on days 0, 7, 14, 21, and 28. Additionally, changes in heart-to-body weight ratio, serum creatine kinase-MB (CK-MB), serum angiotensin-converting enzyme (ACE) ac- tivity, plasma renin activity (PRA), tissue hydroxyproline, and lactate dehydro- genase (LDH) activity, along with histopathological alterations, were evaluated. The administration of AST and RAS-modulating agents reduced ISO-induced changes in cardiac function and biochemical markers. It also demonstrated car- dioprotective effects. Therefore, AST may be useful for treating cardiotoxic HF due to its RAS-regulatory actions. However, further studies are needed to con- firm this therapeutic potential across different HF models and animal species.

Meta-analysis of the efficacy and safety of bispecific antibodies in immune therapy for lung cancer.

2026-03-05T10:06:34+00:00

This work evaluates the efficacy and safety of bispecific antibod- ies (BsAbs) in lung cancer immunotherapy through a meta-analysis, providing more comprehensive evidence for their clinical application. A systematic search was conducted in PubMed, Embase, Cochrane Library, and various Chinese databases to identify eligible randomized controlled trials and quasi-randomized controlled trials. Clinical data on bispecific antibody therapy for lung cancer were collected. The primary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence of immune-related adverse events (irAEs). Data analysis was performed using Rev- Man 5.3 software, with fixed-effect or random-effects models. Nine studies were included, with a total sample size of 588 patients. The meta-analysis revealed no statistically significant differences between the bispecific antibody group and the traditional treatment group in ORR, OS and PFS, with combined effect sizes of odds ratio (OR)=1.31 and 95% confidence interval (CI)=0.98-1.76, OR=1.36 and 95%CI=0.99-1.87 and OR=1.07 and 95%CI=0.80-1.43, respectively (p 0.07, 0.06, and 0.64, respectively). However, the incidence of irAEs was significantly lower in the bispecific antibody group (OR = 1.56; p = 0.0007), indicating a reduction in such events. Bispecific antibodies demonstrate good safety in lung cancer immunotherapy, particularly in reducing irAEs. Despite some improvements in efficacy (e.g., ORR and OS), BsAbs do not demonstrate a significant superiority over conventional treatments.

Instrucciones a los autores

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Instructions to Authors

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