Prolonged venous bleeding due to traditional treatment with leech bite: a case report

<p>Abstract</p> <p>Introduction</p> <p>The medicinal leech, <it>Hirudo medicinalis</it>, has been used in the treatment of many diseases for thousands of years. In Turkey, it is used most commonly in the management of venous diseases of lower extremities.</p> <p>Case presentation</p> <p>A 25-year-old Turkish woman presented to our emergency room with bleeding from her left leg. She had been treated for varicose veins in her lower extremities with leeches about 24 hours before admission to the emergency room. The bleeding was controlled by applying pressure with sterile gauze upon the wound, and she was discharged. She returned after four hours having started bleeding again. Hemostasis was achieved by vein ligation under local anesthesia.</p> <p>Conclusions</p> <p>Leech bite should be evaluated as a special injury. Prolonged bleeding can be seen after leech bites. In such cases, hemostasis either with local pressure or ligation of the bleeding vessel is mandatory.</p

Relationships of dietary patterns with body composition in older adults differ by gender and PPAR-γ Pro12Ala genotype

Dietary patterns may better capture the multifaceted effects of diet on body composition than individual nutrients or foods. The objective of this study was to investigate the dietary patterns of a cohort of older adults, and examine relationships of dietary patterns with body composition. The influence of a polymorphism in the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene was considered. The Health, Aging and Body Composition (Health ABC) Study is a prospective cohort study of 3,075 older adults. Participants’ body composition and genetic variation were measured in detail. Food intake was assessed with a semi-quantitative food frequency questionnaire (Block Dietary Data Systems, Berkeley, CA), and dietary patterns of 1,809 participants with complete data were derived by cluster analysis. Six clusters were identified, including a ‘Healthy foods’ cluster characterized by higher intake of low-fat dairy products, fruit, whole grains, poultry, fish and vegetables. An interaction was found between dietary patterns and PPAR-γ Pro12Ala genotype in relation to body composition. While Pro/Pro homozygous men and women in the ‘Healthy foods’ cluster did not differ significantly in body composition from those in other clusters, men with the Ala allele in the ‘Healthy foods’ cluster had significantly lower levels of adiposity than those in other clusters. Women with the Ala allele in the ‘Healthy foods’ cluster differed only in right thigh intermuscular fat from those in other clusters. Relationships between diet and body composition in older adults may differ by gender and by genetic factors such as PPAR-γ Pro12Ala genotype

Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial

IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. DESIGN, SETTING, AND PARTICIPANTS: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. INTERVENTIONS: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. MAIN OUTCOMES AND MEASURES: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. RESULTS: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). CONCLUSIONS AND RELEVANCE: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03183141

Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial

IMPORTANCE: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. OBJECTIVES: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. DESIGN, SETTING, AND PARTICIPANTS: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. INTERVENTIONS: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. MAIN OUTCOMES AND MEASURES: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. RESULTS: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). CONCLUSIONS AND RELEVANCE: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03183141

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown

Objective: To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. Design: This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. Results: The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (−6.6%, 95% CI −18.2 to +7.1%, p = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A post-hoc analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions (n = 7,499 in 2020 vs. n = 8,362 in 2019). Conclusion: This ad hoc study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601

Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI. OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities. METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24. RESULTS: TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6-13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression. CONCLUSIONS: VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients

Acute appendicitis caused by endometriosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Endometriosis is a well-recognized gynecological condition in the reproductive age group. Surgical texts present the gynecological aspects of the disease in detail, but the published literature on unexpected manifestations, such as appendiceal disease, is inadequate. The presentation to general surgeons may be atypical and pose diagnostic difficulty. Thus, a definitive diagnosis is likely to be established only by the histological examination of a specimen.</p> <p>Case presentation</p> <p>We report a case of endometriosis of the appendix in a 25-year-old Caucasian woman who presented with symptoms of acute appendicitis and was treated by appendectomy, which resulted in a good outcome.</p> <p>Conclusions</p> <p>We discuss special aspects of acute appendicitis caused by endometriosis to elucidate the pathologic entity of this variant of acute appendicitis.</p

Eukaryotic Y-family polymerases bypass a 3-methyl-2′-deoxyadenosine analog in vitro and methyl methanesulfonate-induced DNA damage in vivo

N3-methyl-adenine (3MeA) is the major cytotoxic lesion formed in DNA by SN2 methylating agents. The lesion presumably blocks progression of cellular replicases because the N3-methyl group hinders interactions between the polymerase and the minor groove of DNA. However, this hypothesis has yet to be rigorously proven, as 3MeA is intrinsically unstable and is converted to an abasic site, which itself is a blocking lesion. To circumvent these problems, we have chemically synthesized a 3-deaza analog of 3MeA (3dMeA) as a stable phosphoramidite and have incorporated the analog into synthetic oligonucleotides that have been used in vitro as templates for DNA replication. As expected, the 3dMeA lesion blocked both human DNA polymerases α and δ. In contrast, human polymerases η, ι and κ, as well as Saccharomyces cerevisiae polη were able to bypass the lesion, albeit with varying efficiencies and accuracy. To confirm the physiological relevance of our findings, we show that in S. cerevisiae lacking Mag1-dependent 3MeA repair, polη (Rad30) contributes to the survival of cells exposed to methyl methanesulfonate (MMS) and in the absence of Mag1, Rad30 and Rev3, human polymerases η, ι and κ are capable of restoring MMS-resistance to the normally MMS-sensitive strain

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown

Objective: To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. Design: This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. Results: The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (−6.6%, 95% CI −18.2 to +7.1%, p = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A post-hoc analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions (n = 7,499 in 2020 vs. n = 8,362 in 2019). Conclusion: This ad hoc study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601