BACKGROUND: Klebsiella pneumoniae carbapenemase-producing K pneumoniae (KPC-Kp) bloodstream infections are associated with high mortality. We studied clinical bloodstream KPC-Kp isolates to investigate mechanisms of resistance to complement, a key host defense against bloodstream infection.
METHODS: We tested growth of KPC-Kp isolates in human serum. In serial isolates from a single patient, we performed whole genome sequencing and tested for complement resistance and binding by mixing study, direct enzyme-linked immunosorbent assay, flow cytometry, and electron microscopy. We utilized an isogenic deletion mutant in phagocytosis assays and an acute lung infection model.
RESULTS: We found serum resistance in 16 of 59 (27%) KPC-Kp clinical bloodstream isolates. In 5 genetically related bloodstream isolates from a single patient, we noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ. Disruption of wcaJ was associated with decreased polysaccharide capsule, resistance to complement-mediated killing, and surprisingly, increased binding of complement proteins. Furthermore, an isogenic wcaJ deletion mutant exhibited increased opsonophagocytosis in vitro and impaired in vivo control in the lung after airspace macrophage depletion in mice.
CONCLUSIONS: Loss of function in wcaJ led to increased complement resistance, complement binding, and opsonophagocytosis, which may promote KPC-Kp persistence by enabling coexistence of increased bloodstream fitness and reduced tissue virulence.

BACKGROUND: Streptococcus pneumoniae serotype 3 remains a problem globally. Malawi introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2011, but there has been no direct protection against serotype 3 carriage. We explored whether vaccine escape by serotype 3 is due to clonal expansion of a lineage with a competitive advantage.
METHODS: The distribution of serotype 3 Global Pneumococcal Sequence Clusters (GPSCs) and sequence types (STs) globally was assessed using sequences from the Global Pneumococcal Sequencing Project. Whole-genome sequences of 135 serotype 3 carriage isolates from Blantyre, Malawi (2015-2019) were analyzed. Comparative analysis of the capsule locus, entire genomes, antimicrobial resistance, and phylogenetic reconstructions were undertaken. Opsonophagocytosis was evaluated using serum samples from vaccinated adults and children.
RESULTS: Serotype 3 GPSC10-ST700 isolates were most prominent in Malawi. Compared with the prototypical serotype 3 capsular polysaccharide locus sequence, 6 genes are absent, with retention of capsule polysaccharide biosynthesis. This lineage is characterized by increased antimicrobial resistance and lower susceptibility to opsonophagocytic killing.
CONCLUSIONS: A serotype 3 variant in Malawi has genotypic and phenotypic characteristics that could enhance vaccine escape and clonal expansion after post-PCV13 introduction. Genomic surveillance among high-burden populations is essential to improve the effectiveness of next-generation pneumococcal vaccines.

UNASSIGNED: To explore the surgical technique and preliminary safety and aesthetic results of endoscopic removal of injectable Amazingel with/without immediate prepectoral implant-based breast augmentation for patients.
UNASSIGNED: The clinical data of 25 patients who underwent endoscopic removal of injectable Amazingel with/without immediate prepectoral implant-based breast augmentation between April 2020 and January 2024 and met the selection criteria was retrospective analysed. The patients\' age ranged from 33 to 73 years, with a mean of 50.4 years, and the body mass index ranged from 16.8 to 26.6 kg/m 2, with a mean of 21.5 kg/m 2. They were all bilaterally injected with Amazingel, and the time between initial injections and surgery ranged from 17 to 26 years, with a mean of 21.4 years. Early safety was evaluated by the incidence of early postoperative complications, and early aesthetic results were evaluated using Harris scores (including breast shape satisfaction, sensation satisfaction, and elasticity satisfaction) at 3 months after operation.
UNASSIGNED: There were 9 cases underwent Amazingel removal (group A) and 16 cases underwent Amazingel removal with immediate prepectoral implant-based breast augmentation (group B). Intraoperative removal of Amazingel ranged from 808 to 1 285 mL, with a mean of 1 050.7 mL; the mass of the capsule removed ranged from 36 to 169 g, with a mean of 103.6 g; and a gross anatomical prosthesis was used with a median size of 345 mL (range, 315-355 mL). The operation time ranged from 95 to 395 minutes, with a mean of 194.2 minutes; and the cost of the procedure ranged from 8000to 91 000 yuan, with a mean of 33 000 yuan. Patients had a median follow-up time of 22.7 months (range, 3.0-48.1 months). There was 1 case of intraoperative skin burn due to the operation of the electric scalpel, which healed naturally after operation without flap necrosis. There was no adverse conditions such as prosthesis outline showing, ripple sign, and capsular contracture during follow-up; a small amount of Amazingel residue was found in 2 patients at 1 year after operation. The Harris score at 3 months after operation was used to evaluate the early aesthetic results, and the breast shape, elasticity, and sensation satisfaction of group A were lower than group B, but the differences between the two groups were not significant ( P>0.05).
UNASSIGNED: Endoscopic removal of injectable Amazingel with/without immediate prepectoral implant-based breast augmentation is safe in the early stage with good aesthetic results, and it is also recommended that patients who had the indications for combined immediate breast augmentation after removal to rebuild the breast appearance.
UNASSIGNED: 探讨腔镜奥美定取出联合或不联合即刻胸肌前假体植入隆胸的手术方法、早期安全性及美容学效果。.
UNASSIGNED: 回顾分析2020年4月—2024年1月收治且符合选择标准的25例行腔镜奥美定取出联合或不联合即刻胸肌前假体植入隆胸术的患者临床资料。患者年龄33～73岁，平均50.4岁；身体质量指数16.8～26.6 kg/m 2，平均21.5 kg/m 2。均为双侧注射奥美定，初次注射至该次手术时间17～26年，平均21.4年。早期安全性通过术后早期并发症发生率进行评估，早期美容学效果采用术后3个月Harris评分（包括乳房外形满意度、感觉满意度、弹性满意度）进行评估。.
UNASSIGNED: 单纯行奥美定取出9例（A组），奥美定取出联合即刻胸肌前假体植入隆胸16例（B组）。术中取出奥美定808～1 285 mL，平均1 050.7 mL；取出包膜质量36～169 g，平均103.6 g；均使用毛面解剖型假体，大小315～355 mL，中位大小345 mL。手术时间95～395 min，平均194.2 min；手术费用0.8～9.1万元，平均3.3万元。患者均获随访，随访时间3.0～48.1个月，中位时间22.7个月。术中因电刀操作导致皮肤烫伤1例，术后自然愈合，无皮瓣坏死；术后3个月内均未发生术区出血、切口裂开、皮下积气、皮瓣坏死等并发症；随访期间均未出现假体轮廓显现、波纹征、包膜挛缩等不良情况；术后1年复查发现2例患者有少量奥美定残留。术后3个月采用Harris评分评定早期美容学效果，A组乳房外形满意度、感觉满意度、弹性满意度均低于B组，但两组差异无统计学意义（ P>0.05）。.
UNASSIGNED: 腔镜奥美定取出联合或不联合胸肌前假体植入隆胸术，术后早期均安全可靠，且具有良好的美容学效果；对于符合适应证的患者建议在奥美定取出后联合即刻假体植入隆胸术，重塑乳房外形。.

UNASSIGNED: Andrographis paniculata (Burm.f.) Nees has been recommended to relieve symptoms and decrease the severity of COVID-19. The clinical study aimed to investigate the efficacy and safety of A. paniculata ethanolic extract (APE).
UNASSIGNED: The efficacy and safety of APE in asymptomatic or mildly symptomatic COVID-19 patients compared with placebo were investigated through a prospective, double-blind randomized control trial. Patients received APE containing 60 mg of andrographolide, three times a day for five days. WHO progression scale, COVID-19 symptoms, and global assessment evaluated the efficacy and adverse events, liver and renal functions were monitored for safety.
UNASSIGNED: 165 patients completed the study (83 patients in the APE group and 82 patients in the placebo group). The highest WHO progression scale was 4 and COVID-19 symptoms were significantly relieved on the last day of intervention in both groups, with no significant difference between groups. APE significantly relieved headache symptoms on day 1 and olfactory loss symptoms on day 2 compared to placebo. The global assessment showed that 80.7% of patients had total recovery after 5-day treatment with APE. Mild diarrhea was the most common side effect with a high dose that resolved within a few days. No hepatic or renal toxicity was associated with treatment.
UNASSIGNED: APE at 180 mg/day for 5 days did not reduce COVID-19 progression in asymptomatic or mildly afflicted COVID-19 patients, however, it shortened the symptoms of olfactory loss with no adverse effects over 5 days of use.

Isolated volar distal radioulnar joint (DRUJ) dislocation is a rare condition with only a few cases reported in the literature. Its diagnosis is often overlooked in the acute phase, and there is no consensus in its management. We present the case of a 20-year-old male patient with an isolated volar radioulnar dislocation, together with a review of the literature. The aim is to present and summarize the acute management of this condition and propose a therapeutic algorithm.

UNASSIGNED: Clostridioides difficile infections (CDI) continue to pose a challenge for clinicians. Fecal microbiota transplantation (FMT) is an effective treatment option in CDI. Furthermore, recent and ongoing studies suggest potential benefits of FMT in other diseases as well.
UNASSIGNED: We would like to present a novel protocol for encapsulation of lyophilized fecal material. Our method provides with better compliance as well as improved flexibility, storage and safety.
UNASSIGNED: FMT was conducted in 28 patients with an overall success rate of 82,14% using apsules containing lyophilized stool. 16 of patients were given capsules with lessened bacteria counts. The success rate in this group was 93,75%.
UNASSIGNED: The results highlight the still unanswered questions about the mechanism of action and contribute to a wider use of FMT in the clinical praxis and in research.

This study aims to evaluate and determine the correlation between in vitro release and in vivo pharmacokinetics of two extended-release dosage forms of Cilostazol. In vitro release profiles for two dosage forms, tablet and capsule, were analyzed under physiologically mimicked medium conditions using the paddle and basket USP release apparatus. A single-dose, two-period crossover study design in beagle dogs was applied for the pharmacokinetic study. The fed and fast effects were considered for evaluation. Pseudo gastric release medium transfer setup study from pH 1.2 to pH 6.8 (+0.5% SLS) and pH 1.2 to pH 6.8 (+1.0% SLS) demonstrated that Pletaal® SR 200 mg capsules have higher drug release rates than Cilostan® CR 200 mg tablets. Similarly, in vivo study showed Cilostazol concentration in plasma and AUC was lower under the fast state than the fed state. The ratio of least squared geometric mean values, Cmax, AUC0-t, and AUC0-inf of Cilostazol were 2.53-fold, 2.89-fold, and 2.87-fold higher for Pletaal® SR 200 mg capsules compared with Cilostan® CR 200 mg tablets, respectively. Correlation of in vitro/in vivo data indicated that Pletal® SR 200 mg capsules have better release and pharmacodynamic effect than Cilostan® CR 200 mg tablets.

While functional endoscopic evaluation of swallowing (FEES) is the most useful diagnostic test for the evaluation of dysphagia, it cannot evaluate the esophageal phase of swallowing. To evaluate if a modification for the FEES exam by swallowing an empty capsule and screening of the upper esophagus could be used for early detection of esophageal dysphagia. A prospective, single-center, pilot study. At the end of a standard FEES exam, the patients were asked to swallow an empty capsule. Fifteen seconds later, the endoscope was inserted into the upper esophagus. A pathological capsule test was defined when the capsule was seen in the esophagus. In such cases, the patient was advised to undergo a gastroscopy, MBS, or esophageal manometry, which were compared to the results of the capsule test. The capsule test was utilized in 109 patients. A pathological capsule test was found in 55 patients (57.8%). In 48 patients (87.3%), an isolated or combined esophageal dysphagia was seen. The accuracy value of the capsule test compared to gastroenterology tests was 83.3%, sensitivity 88.46%, specificity 75%, PPV 85%, and NPV 80%. A modification of the standard FEES exam by including an empty capsule swallow test with an upper esophagus examination may provide a useful screening tool for esophageal dysphagia.

A new, sensitive, and rapid isocratic reversed phase chromatographic method (RP-HPLC-UV) was developed for simultaneous separation of two newly co-formulated antiulcer mixtures; Amoxicillin, Vonoprazan and Clarithromycin [Mixture (I)], and Amoxicillin, Lansoprazole and Clarithromycin [Mixture (II)]. Analytical separation was performed using a Promosil C18 column and ultraviolet detection at 210 nm. The separation was achieved within only 8 min. For both mixtures, an aqueous solution, composed of (Acetonitrile: Methanol: 0. 2 M phosphoric acid) within ratio of (30: 30: 40) adjusted to final pH 3.0, was the mobile phase. This method was validated as per the International Conference on Harmonization guidelines. The linearity ranges of these proposed method of the (Mixture (I)) were 25.0-400.0 µg/mL Amoxicillin, 0.5-8.0 µg/mL Vonoprazan, and 12.5-200.0 µg/mL Clarithromycin. And the linearity ranges of the (Mixture (II)) were 10.0-300.0 µg/mL Amoxicillin, 0.3-9.0 µg/mL Lansoprazole and 5.0-150.0 µg/mL Clarithromycin. This method was firstly applied for effective separation of Amoxicillin, Vonoprazan and Clarithromycin [Mixture (I)]. It fulfilled good repeatability, sensitivity, and accuracy (R.S.D. < 2.0%). The mean recoveries of the analytes in their Tri-Pak formulations were acceptable. The greenness of the developed chromatographic methods was assessed using an Eco-scale method and it was applied for content uniformity testing as per the United States Pharmacopoeia (USP) and the acceptance value of Amoxicillin, in Mixture (I) was 2.88, the acceptance values for Amoxicillin, Lansoprazole in Mixture (II) were 2.592, 2.424, respectively.

UNASSIGNED: A distinct strain of Klebsiella pneumoniae (K. pneumoniae) referred to as hypervirulent (hvKp) is associated with invasive infections such as pyogenic liver abscess in young and healthy individuals. In South Africa, limited information about the prevalence and virulence of this hvKp strain is available. The aim of this study was to determine the prevalence of hvKp and virulence-associated factors in K. pneumoniae isolates from one of the largest tertiary hospitals in a South African province.
UNASSIGNED: A total of 74 K. pneumoniae isolates were received from Pelonomi Tertiary Hospital National Health Laboratory Service (NHLS), Bloemfontein. Virulence-associated genes (rmpA, capsule serotype K1/K2, iroB and irp2) were screened using Polymerase Chain Reaction (PCR). The iutA (aerobactin transporter) gene was used as a primary biomarker of hvKp. The extracted DNAs were sequenced using the next-generation sequencing pipeline and the curated sequences were used for phylogeny analyses using appropriate bioinformatic tools. The virulence of hvKp vs. classical Klebsiella pneumoniae (cKp) was investigated using the Caenorhabditis elegans nematode model.
UNASSIGNED: Nine (12.2%) isolates were identified as hvKp. Moreover, hvKp was significantly (p < 0.05) more virulent in vivo in Caenorhabditis elegans relative to cKp. The virulence-associated genes [rmpA, iroB, hypermucoviscous phenotype (hmv) phenotype and capsule K1/K2] were significantly (p < 0.05) associated with hvKp. A homology search of the curated sequences revealed a high percentage of identity between 99.8 and 100% with other homologous iutA gene sequences of other hvKp in the GenBank.
UNASSIGNED: Findings from this study confirm the presence of hvKp in a large tertiary hospital in central South Africa. However, the low prevalence and mild to moderate clinical presentation of infected patients suggest a marginal threat to public health. Further studies in different settings are required to establish the true potential impact of hvKp in developing countries.