Stereotactic body radiotherapy for painful spinal metastases: a decade of experience at a single institution.

OBJECTIVE: This study aimed to retrospectively evaluate the efficacy of stereotactic body radiotherapy (SBRT) for pain relief in patients with painful spinal bone metastases (SBMs) and to identify key factors contributing to treatment outcomes. METHODS: The authors conducted a retrospective analysis of adult patients who underwent SBRT for painful solid tumor SBMs between March 2012 and January 2023. During this period, SBRT was performed adhering to the International Spine Radiosurgery Consortium guidelines and international consensus recommendations for target volume delineation. To be included, patients needed to experience persistent pain directly associated with SBMs, warranting regular opioid treatment. Positive pain relief post-SBRT was defined by three criteria: 1) a decrease in the severity of pain; 2) reduction in opioid dosage; and 3) concurrent improvement in daily activities. The revised Tokuhashi score and Spine Instability Neoplastic Score were used to identify crucial factors influencing treatment outcomes. RESULTS: This study included 377 patients, covering 576 lesions across 759 vertebrae. Of these, 332 lesions showed significant pain relief within 3 months following SBRT. Lower pain relief rates were observed in patients with a revised Tokuhashi score of 0-8 or in patients with diabetes mellitus. In contrast, higher relief rates were linked to treating a single painful SBM in 1 SBRT course, and greater contouring of the involved sectors according to International Spine Radiosurgery Consortium guidelines and international consensus recommendations. The highest pain relief rate was observed in patients with prostate cancer (73.8%), whereas the lowest rate was observed in patients with hepatocellular carcinoma (36.4%). The presence of pre-SBRT vertebral fractures, the dosage and fraction of SBRT, and the use of concurrent systemic cancer therapies or antiresorptive agents, including bisphosphonates and denosumab, did not notably influence the pain relief efficacy of SBRT. Comprehensive medical records 6 months after SBRT treatment were available for only 362 lesions. The overall rate of pain relief observed was 32.6%. CONCLUSIONS: SBRT is an effective treatment approach for managing painful SBMs, achieving a pain relief rate of 57.6% within 3 months and maintaining a rate of 32.6% at 6 months after treatment. The transition to osteoblastic lesions may potentially improve the stability of SBMs, indicated by lower Spine Instability Neoplastic Score, which in turn could extend pain relief management.

Tumour growth inhibitory effect of Ibervillea sonorae phytopreparations in cervical cancer xenografts.

Cucurbitacin IIb, a triterpene obtained from the Ibervillea sonorae plant, reduces tumour development in a preclinical model of cervical cancer. Acetison and Etanison, phytopreparations made from I. sonorae, present biological activity analogous to CIIb in HeLa. This research evaluated the tumour growth inhibitory effect of these phytopreparations in a HeLa xenograft tumour model in BALB/c nude mice. Tumours in mice were treated every 3 days for 12 days with cisplatin (2 mg/kg), CIIb (5 mg/kg), Acetison (20 mg/kg), Etanison (30 mg/kg), and DMSO at 2%. For histological observations, tumours were stained with H&E. Fingerprinting of both phytopreparations was performed using HPLC-UV and UHPLC-APCI-IT-MS. Both phytopreparations and CIIb inhibit tumour development as well as Cisplatin (75.5%); Etanison (77.7%), Acetison (73.6%), and CIIb (73.0%). Furthermore, only tumours treated with cisplatin showed invasion of bone tissue. The results show the potential use of I. sonorae phytopreparations in the treatment of cervical cancer.

Alternative ergosterol biosynthetic pathways confer antifungal drug resistance in the human pathogens within the Mucor species complex.

Mucormycoses are emerging fungal infections caused by a variety of heterogeneous species within the Mucorales order. Among the Mucor species complex, Mucor circinelloides is the most frequently isolated pathogen in mucormycosis patients and despite its clinical significance, there is an absence of established genome manipulation techniques to conduct molecular pathogenesis studies. In this study, we generated a spontaneous uracil auxotrophic strain and developed a genetic transformation procedure to analyze molecular mechanisms conferring antifungal drug resistance. With this new model, phenotypic analyses of gene deletion mutants were conducted to define Erg3 and Erg6a as key biosynthetic enzymes in the M. circinelloides ergosterol pathway. Erg3 is a C-5 sterol desaturase involved in growth, sporulation, virulence, and azole susceptibility. In other fungal pathogens, erg3 mutations confer azole resistance because Erg3 catalyzes the production of a toxic diol upon azole exposure. Surprisingly, M. circinelloides produces only trace amounts of this toxic diol and yet, it is still susceptible to posaconazole and isavuconazole due to alterations in membrane sterol composition. These alterations are severely aggravated by erg3Δ mutations, resulting in ergosterol depletion and, consequently, hypersusceptibility to azoles. We also identified Erg6a as the main C-24 sterol methyltransferase, whose activity may be partially rescued by the paralogs Erg6b and Erg6c. Loss of Erg6a function diverts ergosterol synthesis to the production of cholesta-type sterols, resulting in resistance to amphotericin B. Our findings suggest that mutations or epimutations causing loss of Erg6 function may arise during human infections, resulting in antifungal drug resistance to first-line treatments against mucormycosis. IMPORTANCE: The Mucor species complex comprises a variety of opportunistic pathogens known to cause mucormycosis, a potentially lethal fungal infection with limited therapeutic options. The only effective first-line treatments against mucormycosis consist of liposomal formulations of amphotericin B and the triazoles posaconazole and isavuconazole, all of which target components within the ergosterol biosynthetic pathway. This study uncovered M. circinelloides Erg3 and Erg6a as key enzymes to produce ergosterol, a vital constituent of fungal membranes. Absence of any of those enzymes leads to decreased ergosterol and consequently, resistance to ergosterol-binding polyenes such as amphotericin B. Particularly, losing Erg6a function poses a higher threat as the ergosterol pathway is channeled into alternative sterols similar to cholesterol, which maintain membrane permeability. As a result, erg6a mutants survive within the host and disseminate the infection, indicating that Erg6a deficiency may arise during human infections and confer resistance to the most effective treatment against mucormycoses.

Rational use of short-term anorectic drugs for one-year effective treatment of obesity: An analysis of four studies.

BACKGROUND: Obesity is a complex disease for which pharmacotherapy is often used. Anti-obesity drugs (AODs) are characterized by inducing a variable inter-subject body weight reduction (BWR), the attainment of a plateau after their maximal effect is achieved, and weight regain after drug discontinuation, which complicate individualized treatment of obesity. OBJECTIVE: This exploratory analysis aimed to compare the first-month body weight reduction in kg (1mo-BWRkg) and tolerance development (moT) of four known interventions with low (placebo), intermediate (phentermine or mazindol monotherapy), and high (5 active ingredients fixed-dose combination) efficacy, as predictors of their 6-month body weight reduction efficacy in percent (6mo-BWR%). In addition, a detailed analysis of the 6-to-12-month BWR follow-up in subjects under orlistat or diet and exercise regimens was performed. MATERIALS AND METHODS: The analysis included 662 adult subjects with obesity. After the construction of average efficacy and weight rebound curves, subjects were grouped into various 1mo-BWRkg, moT, and 6mo-BWR% intervals, or 6-month body weight rebound parameters for further evaluation. RESULTS: The 6mo-BWR% efficacy level of interventions was confirmed, although a general high intersubject variation was observed. 1mo-BWRkg + moT was found as an acceptable predictor of 6mo-BWR%. Between 50 and 80% of the 6-to-12-month follow-up completers maintained at least 5% BWR%. CONCLUSION: Short-term AODs are useful adjuvants for the 1-year rational treatment of obesity. 1mo-BWRkg + moT is an acceptable parameter to predict the 6mo-BWR% efficacy of these interventions.

Perspectives on carboxylates generation from Ecuadorian agro-wastes.

Carboxylates generation from banana (peel and pulp), coffee, and cacao fermentation agro-waste, upon uncontrolled and controlled pHs of 6.6 (heat-driven methanogens inactivation) and 5.2 (pH inactivation), was studied. Regarding volatile fatty acids (VFAs), acetic was the highest for cocoa (96.2 g kg-1TVS) at pH 4.5. However, butyric was relevant for banana pulp (90.7 g kg-1TVS), at controlled pH 6.6. The highest medium chain fatty acid (MCFAs) level was hexanoic (cocoa, 3.5 g kg-1TVS), while octanoic reached a maximum of 2.8 g kg-1TVS for coffee at pH 6.6. At pH 5.2 MCFAs yield was relatively low. Uncontrolled pH conditions, using banana resulted in superior VFAs production compared to controlled conditions. Thus, pH became a determining variable when deciding the time and kind of carboxylic acid to be recovered. The bacterial community at the end of the chain elongation process was dominated by phyla Firmicutes, and Clostridium as the most common genera.

Intergenerational Solidarity During Emerging Adulthood: Associations with Psychological Distress and Satisfaction with Life in Southern Europe.

Background: Intergenerational solidarity between parents and emerging adult offspring requires more substantial attention at the present time. Changing demographic structures and transformations in family dynamics over recent decades have increased both opportunities and the need for parent-child interactions and exchanges of support and affection during emerging adulthood. Purpose: The study had two aims: first, to explore patterns in intergenerational solidarity in accordance with different sociodemographic characteristics of emerging adults; and second, to analyse associations between intergenerational solidarity and emerging adults' psychological distress and satisfaction with life. Methods: Participants were 644 emerging adult university students from Southern Europe (Spain and Portugal), aged between 18 and 29 years, who completed a self-report questionnaire designed to assess variables linked to sociodemographic aspects (gender, country of residence, sexual orientation, living status, family income), intergenerational solidarity, psychological distress and satisfaction with life. Results: The results indicated some differences in intergenerational solidarity patterns in accordance with a range of sociodemographic characteristics. They also revealed significant associations between intergenerational solidarity dimensions and emerging adults' satisfaction with life and psychological distress. Moreover, affective solidarity was found to fully mediate the relationship between associational, functional and normative solidarity and emerging adults' adjustment. In the case of conflictual solidarity, affective solidarity was found to partially mediate the relationship between this dimension of intergenerational solidarity and emerging adults' distress and to fully mediate the relationship between this same dimension and emerging adults' satisfaction with life. Conclusion: The results indicate that it is important to take sociodemographic diversity into account when exploring relationships between emerging adults and their parents. They also suggest that affective solidarity acts as a protective factor in promoting emerging adults' adjustment.

A Randomized Control Trial of Dexketoprofen/Vitamin B (Thiamine, Pyridoxine and Cyanocobalamin) Fixed-Dose Combination in Post-Traumatic Grade I-II Cervical Sprains.

BACKGROUND: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders. OBJECTIVE: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains. METHODS: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0. RESULTS: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC. CONCLUSIONS: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains. CLINICAL TRIALS REGISTRATION: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).

Primary Stereotactic Body Radiotherapy for Spinal Bone Metastases From Lung Adenocarcinoma.

OBJECTIVE: This study aimed to assess the results of primary stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM) originating from lung adenocarcinoma (ADC). We considered the revised Tokuhashi score (rTS), Spinal Instability Neoplastic Score (SINS), and genetic characteristics. METHODS: We examined adult patients with lung ADC who underwent primary SBRT (using the CyberKnife System) for SBM between March 2012 and January 2023. RESULTS: We analyzed data from 99 patients, covering 152 SBM across 194 vertebrae. The overall local control (LC) rate was 77.6% for SBM from lung ADC, with a LC rate of 90.7% at 1 year. The median period for local progression (LP) occurrence was recorded at 10.0 (3-52) months. Additionally, Asian patients demonstrated higher LC rates than White patients. Utilizing the rTS and SINS as predictive tools, we revealed that a poor survival prognosis and an unstable spinal structure were associated with increased rates of LP. Furthermore, the presence of osteolytic bone destructions and pain complaints were significantly correlated with the occurrence of LP. In the cohort of this study, 108 SBM underwent analysis to determine the expression levels of programmed cell death ligand 1 (PD-L1). Additionally, within this group, 60 showed mutations in the epidermal growth factor receptor (EGFR) alongside PD-L1 expression. Nevertheless, these genetic differences did not result in statistically significant differences in the LC rate. CONCLUSION: The one-year LC rate for primary SBRT targeting SBM from lung ADC stood at 90.7%, particularly with the use of the CyberKnife System. Patients achieving LC exhibited significantly longer survival times compared to those with LP.

Targeting LxCxE cleft pocket of retinoblastoma protein in M2 macrophages inhibits ovarian cancer progression.

Ovarian cancer remains a major health threat with limited treatment options available. It is characterized by immunosuppressive tumor microenvironment (TME) maintained by tumor- associated macrophages (TAMs) hindering anti-tumor responses and immunotherapy efficacy. Here we show that targeting retinoblastoma protein (Rb) by disruption of its LxCxE cleft pocket, causes cell death in TAMs by induction of ER stress, p53 and mitochondria-related cell death pathways. A reduction of pro-tumor Rb high M2-type macrophages from TME in vivo enhanced T cell infiltration and inhibited cancer progression. We demonstrate an increased Rb expression in TAMs in women with ovarian cancer is associated with poorer prognosis. Ex vivo, we show analogous cell death induction by therapeutic Rb targeting in TAMs in post-surgery ascites from ovarian cancer patients. Overall, our data elucidates therapeutic targeting of the Rb LxCxE cleft pocket as a novel promising approach for ovarian cancer treatment through depletion of TAMs and re-shaping TME immune landscape. Statement of significance: Currently, targeting immunosuppressive myeloid cells in ovarian cancer microenvironment is the first priority need to enable successful immunotherapy, but no effective solutions are clinically available. We show that targeting LxCxE cleft pocket of Retinoblastoma protein unexpectedly induces preferential cell death in M2 tumor-associated macrophages. Depletion of immunosuppressive M2 tumor-associated macrophages reshapes tumor microenvironment, enhances anti-tumor T cell responses, and inhibits ovarian cancer. Thus, we identify a novel paradoxical function of Retinoblastoma protein in regulating macrophage viability as well as a promising target to enhance immunotherapy efficacy in ovarian cancer.

Pregnancy-associated atypical hemolytic uremic syndrome. Case report.

Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare disease. There are only few reports in the literature, and most are in the puerperium period. It is a thrombotic microangiopathy (TMA) characterized for microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. We report the case of a pregnant patient at 26.3 gestation weeks, who developed clinical features of TMA, neurological alterations, and septic shock; then after fetus and placental delivery, no clinical improvement was observed; a diagnostic protocol was performed due to suspicion of P-aHUS, showing improvement after the plasma exchange sessions and eculizumab. We present here a brief review of the case since it is an entity that needs to be suspected during pregnancy when TMA features and requires an immediate diagnosis to provide timely treatment.

Institutional Betrayal in the Criminal and Civil Legal Systems: Exploratory Factor Analysis with a Sample of Black and Hispanic Survivors of Intimate Partner Violence.

Institutional betrayal (IB) is well-documented among survivors of gender-based violence seeking help and/or reporting incidents of violence in various settings, including college campuses and health care settings. Two of the most common institutions from which survivors seek help are the criminal and civil legal systems; however, less is known about the experiences of IB among survivors interfacing with those systems. Previous studies exploring IB have implemented the Institutional Betrayal Questionnaire (IBQ) and its various adaptations, but this scale has not yet been analyzed in the criminal or civil legal context, nor has it been analyzed among racially marginalized survivors. This paper explores the potential for utilizing the IBQ-Health among a sample of 199 Black and Hispanic survivors of intimate partner violence (IPV) who sought help from the criminal and/or civil legal system(s). An exploratory factor analysis was conducted to explore the fit of the measure to the data. Results suggest that the measure as it has previously been used does not demonstrate strong reliability or fit with this population or institution. Possible explanations and future directions are explored, including support for developing and piloting a new measure to assess IB among Black and Hispanic survivors of interpersonal violence who are seeking help from criminal and civil legal institutions.

Synergistic Antinociceptive Effect of ß-Caryophyllene Oxide in Combination with Paracetamol, and the Corresponding Gastroprotective Activity.

Pain is the most frequent symptom of disease. In treating pain, a lower incidence of adverse effects is found for paracetamol versus other non-steroidal anti-inflammatory drugs. Nevertheless, paracetamol can trigger side effects when taken regularly. Combined therapy is a common way of lowering the dose of a drug and thus of reducing adverse reactions. Since ß-caryophyllene oxide (a natural bicyclic sesquiterpene) is known to produce an analgesic effect, this study aimed to determine the anti-nociceptive and gastroprotective activity of administering the combination of paracetamol plus ß-caryophyllene oxide to CD1 mice. Anti-nociception was evaluated with the formalin model and gastroprotection with the model of ethanol-induced gastric lesions. According to the isobolographic analysis, the anti-nociceptive interaction of paracetamol and ß-caryophyllene oxide was synergistic. Various pain-related pathways were explored for their possible participation in the mechanism of action of the anti-nociceptive effect of ß-caryophyllene oxide, finding that NO, opioid receptors, serotonin receptors, and K+ATP channels are not involved. The combined treatment showed gastroprotective activity against ethanol-induced gastric damage. Hence, the synergistic anti-nociceptive effect of combining paracetamol with ß-caryophyllene oxide could be advantageous for the management of inflammatory pain, and the gastroprotective activity should help to protect against the adverse effects of chronic use.

Microfilaremic infection in canine filariosis in Colombia: a challenge in morphological and molecular diagnostics.

Canine filariosis is caused by filiform nematodes and affects several species of animals as well as humans. The disease produces a wide range of symptoms that can often be confused with other diseases, which increases the complexity of its diagnosis. The search for methodologies to facilitate its diagnosis is a challenge, and specific and differential identification of the parasite species causing the disease holds key to a successful diagnosis. In Colombia, there is a problem of underdiagnosis of filariosis in microfilaremic dogs infected by Dirofilaria immitis and Acanthocheilonema reconditum, and of microfilaremias not related to heartworm disease. The highest prevalences have been reported for D. immitis infections, although new cases of A. reconditum infections are beginning to appear. The aim of this study was to differentiate the microfilariae infections caused by D. immitis and A. reconditum by a morphological and molecular characterization of microfilariae so as to facilitate an accurate diagnosis of canine filariosis in the metropolitan area of Bucaramanga (Colombia). For this purpose, 400 blood samples with anticoagulants were collected from the dogs and analyzed with the help of a commercial immunochromatography kit for the detection of D. immitis circulating antigen. The Woo, Knott, and polymerase chain reaction (PCR) techniques were employed for determining the parasite count, morphological observation, and molecular identification of microfilariae present in the dogs respectively. The prevalence of microfilaremic dogs in Bucaramanga metropolitan area was 18.75% (75/400). The prevalence of dogs that tested positive for D. immitis in the antigen and in PCR tests was 1.25% (5/400) and 1% (4/400), respectively. Furthermore, the PCR test revealed that 17.75% of the microfilaremic dogs tested positive for A. reconditum (71/400) (first report in the metropolitan area of Bucaramanga), with one animal co-infected by both species, and 0% for D. repens (0/400). However, by morphological characterization, 4% of the microfilariae (3/75) corresponded to D. immitis, 20% (15/75) to D. repens, and 76% (57/75) to A. reconditum. The use of molecular diagnostic methods such as PCR aids in the specific identification of the parasite, thus making it a more accurate method than the morphological characterization of microfilariae. The identification of the parasites by PCR helps improve the veterinary diagnosis of canine filariosis in Colombia, which would lead to the establishment of an appropriate treatment protocol for each species of filaria and also to the generation of reliable data to be used at the clinical and epidemiological levels.

SARS-CoV-2 remodels the landscape of small non-coding RNAs with infection time and symptom severity.

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has significantly impacted global health, stressing the necessity of basic understanding of the host response to this viral infection. In this study, we investigated how SARS-CoV-2 remodels the landscape of small non-coding RNAs (sncRNA) from a large collection of nasopharyngeal swab samples taken at various time points from patients with distinct symptom severity. High-throughput RNA sequencing analysis revealed a global alteration of the sncRNA landscape, with abundance peaks related to species of 21-23 and 32-33 nucleotides. Host-derived sncRNAs, including microRNAs (miRNAs), transfer RNA-derived small RNAs (tsRNAs), and small nucleolar RNA-derived small RNAs (sdRNAs) exhibited significant differential expression in infected patients compared to controls. Importantly, miRNA expression was predominantly down-regulated in response to SARS-CoV-2 infection, especially in patients with severe symptoms. Furthermore, we identified specific tsRNAs derived from Glu- and Gly-tRNAs as major altered elements upon infection, with 5' tRNA halves being the most abundant species and suggesting their potential as biomarkers for viral presence and disease severity prediction. Additionally, down-regulation of C/D-box sdRNAs and altered expression of tinyRNAs (tyRNAs) were observed in infected patients. These findings provide valuable insights into the host sncRNA response to SARS-CoV-2 infection and may contribute to the development of further diagnostic and therapeutic strategies in the clinic.

Depression, Anxiety, and Stress Among Emerging Adult Undergraduates: A Longitudinal and Two-Cohort Study.

Mental disorders constitute one of the population's principal health problems, especially among undergraduates. This quantitative study compared levels of depression, anxiety, and stress in a sample of emerging adult university undergraduates from a gender perspective (1) during the initial and intermediate years of emerging adulthood and (2) in two different cohorts. A total of 383 Spanish emerging adult university undergraduates were monitored longitudinally (2015-2018) and two cohorts were compared (2015-2020). Participants completed the validated Spanish version of the Depression Anxiety Stress Scale-21. Mean-level and rank-order stability was found across the two waves of the longitudinal study in relation to levels of depression, anxiety, and stress. Significant differences were found between the two cohorts, indicating higher levels of psychological distress in 2020 than in 2015. Women were found to have higher levels of psychological distress, particularly stress, than men in both waves and cohorts. Results are discussed in relation to the negative effects of the COVID-19 health crisis on the emotional health of emerging adults. The present study highlights the need to establish measures designed to improve the mental health of emerging adults, which was more severely affected by the COVID-19 crisis than by the aftermath of the 2008 financial crisis. It also underscores the need to develop interventions designed to alleviate the greater degree of stress suffered by women.

Pelvic lymph node involvement and risk of recurrence in HPV-associated endocervical adenocarcinoma stage IA2-IB1 according to Silva's system in two Colombian cancer centers.

OBJECTIVE: To compare the pelvic lymph node involvement and risk of recurrence in patients with human papillomavirus (HPV)-associated endocervical adenocarcinoma stage IA2-IB1 undergoing hysterectomy and/or trachelectomy plus lymphadenectomy, according to Silva's classification system. METHODS: A retrospective cohort study was performed in two Colombian cancer centers. The cases were classified according to the Silva classification system. Clinical, surgical, and histopathological variables were evaluated. Recurrence risk was analyzed by patterns A, B, or C. A logistic regression model was performed for tumor recurrence. The Kaplan-Meier method was used to estimate overall survival and disease-free survival (DFS). A weighted kappa was performed to determine the degree of concordance between pathologists. RESULTS: A total of 100 patients were identified, 33% pattern A, 29% pattern B, and 38% pattern C. The median follow-up time was 42.5 months. No evidence of lymph node involvement was found in patients classified as A and B, while in the C pattern was observed in 15.8% (n = 6) of cases (P < 0.01). There were 7% of cases with recurrent disease, of which 71.5% corresponded to type C pattern. Patients with Silva pattern B and C had 1.22- and 4.46-fold increased risk of relapse, respectively, compared with pattern A. The 5-year DFS values by group were 100%, 96.1%, and 80.3% for patterns A, B, and C, respectively. CONCLUSION: For patients with early-stage HPV-associated endocervical adenocarcinoma, the type C pattern presented more lymph node involvement and risk of recurrence compared to the A and B patterns. The concordance in diagnosis of different Silva's patterns by independents pathologists were good.

Less than whole uterus irradiation for patients with locally advanced cervical cancer.

INTRODUCTION: Current consensus guidelines for definitive cervical cancer intensity modulated radiation therapy (IMRT) recommend inclusion of the entire uterus within the clinical target volume, however this is debated. We aimed to evaluate outcomes of patients with cervical cancer who were treated with less than whole uterus irradiation. METHODS: We identified 109 patients with FIGO Stage IB-IVA cervical cancer treated definitively with concurrent chemoradiation, including IMRT and brachytherapy, from 2010 to 2022 at a single institution where the practice was to include the gross cervix tumor with an internal target volume with differences in bladder filing accounted for, plus additional 5 mm planning target volume (PTV) margin. Local, regional, and distant recurrences were analyzed using competing risk methods, and a Wilcoxon rank sum test was performed to assess differences in dose to organs at risk based on the proportion of the uterus included in the PTV, with the median proportion of the uterus included (75 %) used as the cut-point. RESULTS: The median follow-up time was 65 months (range 3-352 months). The 2-year cumulative incidence of LR for the entire cohort was 4.2 % (95 % confidence interval [CI] 1.3-9.7). Compared with patients who had ≥ 75 % of the uterus included in the PTV, patients who had < 75 % of the uterus included in the PTV had significantly lower bowel D200cc (p = 0.02). The cumulative incidence of local failure (LR) was not significantly different between the two groups. CONCLUSIONS: Including less than the whole uterus for definitive cervix cancer IMRT does not seem to compromise local control. Less than whole uterus irradiation could be considered for carefully selected cervix cancer patients to decrease bowel dose and possible treatment-related toxicity.

Prevented perinatal HIV infections in the era of antiretroviral prophylaxis and treatment, United States, 1994-2020.

OBJECTIVE: The primary aim of this serial cross-sectional analysis is to estimate the total number of prevented perinatal HIV transmissions from the time of the initial recommendation for perinatal zidovudine (ZDV) prophylaxis in 1994 through 2020 in the US. METHODS: The estimated number of prevented transmissions was calculated as annual differences between expected and observed numbers of perinatal HIV transmissions. Annual expected number of transmissions was estimated by multiplying the annual number of births to women with HIV by 0.2255 (22.55%), i.e., the transmission rate of the control group in the ACTG Protocol 076 trial. We used published point estimates or, if only ranges were given, the midpoints of those ranges as the best estimates of the annual numbers of births to women with HIV and infants with perinatal HIV. When data were not available, we linearly interpolated or extrapolated the available data to obtain estimated numbers for each year. RESULTS: Between 1978 and 2020, the approximate number of live births to women with HIV was 191 267 (95% confidence interval [CI] 190 392-192 110) and for infants with diagnosed perinatal HIV, it was 21 379 (95% CI 21 088-21 695). Since 1994, the annual number of infants born with HIV decreased from 1263 (95% CI 1194-1333) to 33 in 2019 (95% CI 22-45) and 36 in 2020 (95% CI 25-48), corresponding to a 97% reduction. Cumulatively, an estimated total of 22 732 (95% CI 21 340-24 462) perinatal HIV infections were prevented from 1994 through to 2020. CONCLUSION: The elimination of perinatal HIV transmission-accompanied by the cumulative number of prevented cases exceeding that of perinatal HIV infections-is a major public health achievement in the US.

Rhodococcus infection: a 10-year retrospective analysis of clinical experience and antimicrobial susceptibility profile.

Rhodococcus equi is an opportunistic pathogen known to cause pulmonary and extrapulmonary disease among immunocompromised patients. Treatment is frequently challenging due to intrinsic resistance to multiple antibiotic classes. While non-equi Rhodococcus spp. are prevalent, their clinical significance is poorly defined. There is also limited data on antibiotic susceptibility testing (AST) of Rhodococcus infection in humans. We conducted a single-center, retrospective cohort study evaluating clinical characteristics, microbiologic profile, and AST of Rhodococcus infections between June 2012 and 2022 at our tertiary academic medical center. Identification of Rhodococcus spp. was performed by Sanger 16S rRNA gene sequencing and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry, and AST was performed by agar dilution. Three hundred twenty-two isolates of Rhodococcus spp. were identified from blood (50%), pulmonary (26%), and bone/joint (12%) sources. R. equi/hoagii, R. corynebacterioides, and R. erythropolis were the most frequently isolated species, with 19% of isolates identified only to genus level. One hundred ninety-nine isolates evaluated for AST demonstrated high-level resistance to amoxicillin/clavulanate, cephalosporins, and aminoglycosides. More than 95% susceptibility to imipenem, vancomycin, linezolid, rifampin, and clarithromycin was observed. Non-equi species showed a significantly more favorable AST profile relative to R. equi. Clinically significant Rhodococcus infection was rare with 10 cases diagnosed (majority due to R. equi) and managed. The majority of patients received 2- or 3-drug combination therapy for 2-6 months, with favorable clinical response. Significant differences in AST were observed between R. equi and non-equi species. Despite high antimicrobial resistance to several antibiotic classes, imipenem and vancomycin remain appropriate empiric treatment options for R. equi. Future research evaluating mechanisms underlying antimicrobial resistance is warranted.