Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan.

Background: Early detection, monitoring, and managing adverse events (AEs) are crucial in optimising treatment for multidrug-resistant tuberculosis (MDR-TB) patients. Objectives: To investigate the incidence, factors, management, and impact of AEs on treatment outcomes in MDR-TB patients. Methods: This study reviewed the medical records of 275 MDR-TB patients at Fatimah Jinnah Institute of Chest Diseases in Quetta, Pakistan. Patient information was collected using a designed data collection form. Mann-Whitney U and Kruskal-Wallis tests examined the difference in AEs occurrences based on patients' characteristics. Multiple binary logistic regression identified factors associated with unsuccessful outcomes, with statistical significance set at a p-value < 0.05. Results: Almost all patients (99.6%) experienced at-least one AE (median = 4/patient, interquartile range:3-6). The most common were GI disturbance (95.3%), arthralgia (80.4%), body pain and headache (61.8%), ototoxicity (61.4%), psychiatric disturbance (44%), hypokalaemia (40.4%), dermatological reactions (26.2%) and hypothyroidism (21.5%). AEs led to treatment modification in 7.3% patients. Educated patients, those with a history of TB treatment, previous use and resistance to any second-line drug had significantly higher number of AEs. A total of 64.0% were declared cured, 3.6% completed treatment, 19.6% died and 12.7.9% were lost to follow-up. Patients' age of 41-60(OR = 9.225) and >60 years(OR = 23.481), baseline body weight of 31-60 kg(OR = 0.180), urban residence(OR = 0.296), and experiencing ototoxicity (OR = 0.258) and hypothyroidism (OR = 0.136) were significantly associated with unsuccessful treatment outcomes. Conclusion: AEs were highly prevalent but did not negatively impact treatment outcomes. Patients at higher risk of developing AEs and unsuccessful outcomes should receive special attention for its early management.

Biofouling control potential of quorum quenching anaerobes in lab-scale anaerobic membrane bioreactors: Foulants profile and microbial dynamics.

Indigenously isolated anaerobes encoding four quorum quenching (QQ) enzymes were applied in immobilized- and bioaugmented forms for their implications on membrane foulants, microbial taxa, and biofouling control. Two identical anaerobic membrane bioreactors (AnMBRs) with different immobilizing media, i.e. silica-alginate (AnMBR-Si) and hollow fiber-alginate (AnMBR-Hf), were sequentially operated for two conventional and three QQ based phases. The synergistic addition of QQ anaerobes in free cells and the immobilized form prolonged the membrane filtration operation by 172 ± 29% and 284 ± 12% in AnMBR-Si and AnMBR-Hf, respectively. Biocake with low surface coverage was prominent during QQ application compared to conventional phases. Despite the better control of AHLs (3OC6-, C6-, 3OC8, C8, and C10-HSL) and AI-2 at various points of QQ phases, the QQ consortium could not maintain a low concentration of signals for longer period. Therefrom, quenching of targeted signal molecules instigate the dominance of microbial species bearing non-targeted quorum sensing mechanism. The QQ significantly altered the biofilm-forming community in mixed liquor, while the members with robust signal transduction systems became dominant to counteract the QQ mechanism and were the ultimate cause of biofouling. The improved methane content in biogas and increased methanogens composition during QQ phases demonstrated the synergism of exogenous and immobilized QQ as the most viable option for long-term AnMBR operation.

Quadruplet heterotopic pregnancy; ectopic managed successfully with laparotomy with subsequent viable intrauterine pregnancy: A case report.

Heterotopic pregnancy is characterized by a concurrent intrauterine and ectopic pregnancy. It can occur after natural conception, however, it is more common with assisted reproductive techniques , when over one embryo is transferred. Quadruplet heterotopic pregnancy is an exceedingly rare subset. Our case describes a woman who presented to the emergency room with amenorrhea for 9 weeks and lower abdominal pain for 3 days. Transvaginal ultrasound revealed three alive intrauterine fetuses and one left tubal ectopic pregnancy (Quadruplet heterotopic pregnancy). Patient benefited from emergent laparotomy with favorable outcome both in the short term and in the long term. In a patient with a history of assisted reproductive techniques, a high index of suspicion is warranted towards extra-uterine pregnancy. Sonologists should precisely look for adnexal mass. The presence of peritoneal free-fluid requires further investigation. The prognosis of intrauterine fetuses is good, provided the ectopic pregnancy is managed timely and in an effective manner.

Genetic insights unraveling quorum quenching potential of indigenous isolates from an anaerobic membrane bioreactor.

Despite a few reports of quorum quenching (QQ) in anaerobic membrane bioreactors (AnMBRs), the sensing, regulation and degradation mechanism for quorum sensing (QS) signals by indigenous QQ isolates have been barely studied. This study employed isolation and screening of indigenous QQ strains from anaerobic sludge for acyl-homoserine lactones (AHLs) degradation and membrane biofouling control. High-quality whole genome sequences of Micrococcus luteus anQ-m1, Bacillus pacificus anQ-h4, and Lysinibacillus capsici anQ-h6 were obtained, with a genome size of 2.5, 5.6, and 4.7 Mbp, respectively. Amidase-encoding amiE was the only QQ gene in anQ-m1, while anQ-h6 carries both amiE and lactonase-encoding aiiB genes. Genes responsible for QS autoinducer synthesis were not identified in anQ-m1 and anQ-h6, suggesting low potential of biofilm promotion via QS. Despite a peptidic QS system responsible for biofilm formation, anQ-h4 bears the most comprehensive QQ system, including amiE-amidase, aiiA-lactonase, CYP102A5-cytochrome oxidoreductase, and lsrK-autoinducer-2 kinase. This study elucidates QS and QQ mechanisms of potential anaerobes and provides fundamentals for designing QQ consortia to effectively control biofouling in AnMBRs.

Concordance Between Clinical and Pathological Response Assessment After Neo-Adjuvant Chemotherapy in Patients With Invasive Lobular Carcinoma.

Background Neo-adjuvant chemotherapy (NAC) is frequently administered in breast carcinoma patients. The clinical response to NAC guides further treatment. The pathological response is not only an independent prognostic factor, but it also guides further treatment and prognosis. Objectives The aim of our study was to find the degree of concordance between clinical and pathological response assessments after NAC in Invasive lobular Carcinoma (ILC) cases by using World Health Organization (WHO) criteria and different pathological systems, respectively. We also tried to identify any useful parameter of clinical assessment that could better correlate with pathologic assessment and provide a better estimation of residual tumor. Methods This retrospective study was conducted on 26 ILC tumors diagnosed in 24 patients who were treated with NAC followed by surgical resection between January 2009 and December 2020. Medical records and microscopy glass slides were reviewed for clinical and pathological response assessments, respectively. Results The pre-treatment tumor area ranged from 1.8-255 cm2 and the mean±SD was 52.2±66.8 cm2. After NAC, complete clinical response was observed in four (15.3%) cases. The clinically assessed mean tumor area significantly reduced from 52.2±66.8 cm2 to 17.2±22.6 cm2 (p-value<0.001). The pathologically assessed mean tumor area (27.4±24.1 cm2) didn't differ significantly from the clinically assessed mean tumor area (17.2±22.6 cm2) (p-value=0.114). Pathologically, the majority of the cases showed partial response, and a complete pathological response was achieved in only two (7.7%) cases. The concordance rates between clinical assessment by the WHO method and pathological assessment of the breast using the Sataloff method, Miller-Payne (MP) system, Residual Cancer Burden system, and Chevallier method were 26.7%, 15.8%, 9%, and 3.5%, respectively, with insignificant p-values. Percentage reduction in clinical size and percentage reduction in tumor cellularity differed significantly (p-value=0.038). Conclusion Clinical response assessment provides a less accurate estimation of residual disease, as it shows poor concordance with pathological assessment using different assessment systems/methods.

Digital Breast Tomosynthesis Versus Additional Diagnostic Mammographic Views for the Evaluation of Asymmetric Mammographic Densities.

Introduction Many young females present with an advanced stage of breast cancer, which has a negative effect on the prognosis. Digital breast tomosynthesis is a new emerging imaging technique that aids in improving the specificity of mammography with subsequent early detection of breast cancer, especially in women with radiographically dense breasts. Tomosynthesis is subjectively preferred to conventional mammography and may offer superior diagnostic accuracy for the evaluation of breast lesions. Method Two breast radiologists retrospectively reviewed asymmetric densities using protocols that were institutional review board-approved in 185 patients aged 18 - 70 years (mean: 48 years) who underwent diagnostic mammography and tomosynthesis. Each asymmetric density was interpreted once with tomosynthesis and once with supplemental mammographic views; both modes included the mediolateral oblique and craniocaudal views in a fully crossed and balanced design by using a five-category Breast Imaging Reporting and Data System (BI-RADS) assessment and a probability-of-malignancy score. If the abnormality persisted and appeared benign or completely disappeared on both modalities, the agreement between additional views and tomosynthesis was determined by calculating Kappa value. If there was a discrepancy between additional views and tomosynthesis, the abnormality was subjected to ultrasound. In our study, 89 asymmetric densities were subjected to ultrasound. Results In a total of 182 cases, 84 (46.15%) were categorized as BIRADS-0; 97 (53.30 %) as BIRADS-I, and one (0.55 %) as BIRADS-II on an additional view. Among the asymmetric densities categorized as BIRADS-0 on additional mammography views, digital breast tomosynthesis categorized 72, six, five, and one patient as BIRADS-0, BIRADS-I, BIRADS-II, and BIRADS-IV, respectively. For densities categorized as BIRADS-I (97) on additional view, digital breast tomosynthesis categorized 10 and 87 densities as BIRADS-0 and BIRADS-I, respectively. No change in the BIRADS category was observed among BIRADS-II and BIRADS-IV. A significant difference was observed with the chi-square test among BIRADS categories assigned by an additional view and digital breast tomosynthesis with a p-value of < 0.001. There was, however, a substantial agreement among additional views and tomosynthesis with a kappa value of 0.767. Conclusion Our study results suggest that tomosynthesis may be equivalent to, if not more equivalent to, additional imaging in the assessment of mammographically-detected asymmetric densities, thus improving BI-RADS classification and patient management.

The selective pressure of quorum quenching on microbial communities in membrane bioreactors.

In conventional membrane bioreactor (MBR) treatment systems, Gram-negative bacterial population appears to be always outnumbered Gram-positive community. Thereby, acyl homoserine lactones (AHLs), major signaling molecules utilized by Gram-negative bacteria, have been targeted for biofouling control in quorum quenching (QQ) based studies. This study investigated the impact of AHL and autoinducer-2 (AI-2)-degrading QQ consortium on the selective accumulation of microbial communities in a QQ MBR (MBR-QQb). The results show that addition of the QQ consortium (in the form of beads) increased the filtration time of MBR-QQb by 3.5 times. The distribution of mixed liquor extracellular polymeric substances (EPS), especially the tightly bound (TB) proteinous EPS and the floc size were strongly affected by the QQ activity, and the endless 'battle' between QQ and quorum sensing (QS). More importantly, QQ induced the significant suppression of Gram-negative bacterial community. The average abundance of Gram-positive bacteria at the genus level in the biocake of MBR-QQb (51%) was significantly higher than that of the control MBR (11%) and the MBR with vacant beads (28%). These findings suggest that an unintended condition is created to favor the growth of Gram-positive bacteria in QQ MBRs, resulting in a distinct microbial social network in both bulk sludge and biocake.

Radiologic Assessment of Cervical Canal Stenosis Using Kang MRI Grading System: Do Clinical Symptoms Correlate with Imaging Findings?

Introduction Magnetic resonance imaging (MRI) is widely used in the evaluation of cervical canal stenosis and spinal cord compression. Kang et al. formulated a new MRI grading system for assessing canal stenosis which takes cord signal change into account. The purpose of the study was to determine the agreement between Kang's grading system and neurological symptoms. Methods  A cross-sectional study was conducted at Aga Khan University Hospital between April 2014 and December 2015. Patients meeting inclusion criteria were enrolled. T2 sagittal and T2 axial MRI images were acquired and reported by a consultant neuroradiologist, in accordance with the MRI grading system suggested by Kang et al. Neurologic clinical symptoms were acquired by the history taken by the principal investigator. More than one neurologic symptoms and Kang MRI grade 2 or 3 were taken as positive evidence of cord compression resulting from canal stenosis. Results Amongst 126 subjects, 54% were females. Mean age of patients was 50.3 ± 14.3 years (range 19-83 years). Average disease duration was 4.61 ± 3.73 (range 1-24 months). In the majority of the patients, the findings were found at the C5-C6 level. 65.1% of patients were identified positive for cervical canal stenosis by Kang grading system. Most common neurological symptoms were pain (99%) and numbness (56%). Cohen's Kappa was run to evaluate the agreement between neurological symptoms and Kang grading system. There was a strong agreement between the two methods, K = 0.81 (95% CI 0.70-0.92), p < 0.001. Conclusion There was a substantial agreement between Kang's grading system and the presence of clinical symptoms. The agreement was greatest in females, older patients, and those with longer duration of symptoms.

Insights into quorum quenching mechanisms to control membrane biofouling under changing organic loading rates.

A quorum quenching (QQ) consortium comprised of both acyl homoserine lactones (AHLs)- and autoinducer-2 (AI-2)-degrading bacteria, either immobilized in polymer-coated alginate beads or in liquid suspension, was examined for fouling control in lab-scale MBRs under both steady and changing organic loading rates (OLRs). Under steady conditions the QQ consortium retarded biofouling by a factor of 3. However, a continuous increase in OLR vastly reduced the effectiveness of QQ bacteria; the biofouling was retarded only by factors of 1.4-1.8. A significant increase in extracellular polymeric substance (EPS), especially loosely-bound EPS in mixed liquor together with an increase in polysaccharide content up to 4 times in EPS resulted from the increase in OLR, was attributed to the impaired QQ efficacy. In control MBRs, cake layer resistance was the major factor (>60%) contributing to the increased trans-membrane pressure, as compared with pore blockage resistance and intrinsic membrane resistance. In contrast, the pore blockage resistance became dominant in QQ MBRs (>40%).