CKD-CHECK toolkit to improve doctors' practice in managing chronic kidney disease rapid progressors: a pilot study in primary care setting.

INTRODUCTION: Chronic kidney disease (CKD) rapid progression is associated with higher risk of end-stage kidney disease and higher mortality rate. Monitoring and recognition of CKD rapid progression is still lacking, however interventions have been shown to improve this. Thus, this study aimed to evaluate the acceptability and feasibility of CKD-CHECK toolkit and preliminary measure the outcome of the CKD-CHECK toolkit in assisting primary care doctor to order further tests for CKD rapid progressors and trigger appropriate nephrology referral. MATERIALS AND METHODS: The CKD-CHECK (CKD-CHECK EGFR Chart in Kidney disease) is a toolkit that was developed to auto-generate patients' eGFR trend using a line graph, displaying the trend visually over a year. It identifies patients with rapid CKD progression, triggers the doctors to order appropriate tests (proteinuria quantification or renal imaging) and helps in decision making (continued monitoring at primary care level or referral to nephrologist). The toolkit was piloted among medical officers practising in a hospital-based primary care clinic treating patients with eGFR<60ml/min/1.73m2 using an interventional before-after study design from February to May 2022. In the preintervention period, the CKD patients were managed based on standard practice. The doctors then used the CKDCHECK toolkit on the same group of CKD patients during the intervention period. The feasibility and acceptability of the toolkit was assessed at the end of the study period using the Acceptability of Intervention Measure (AIM) and Feasibility of Intervention Measure (FIM) questionnaires. All patients' clinical data and referral rate were collected retrospectively through medical files and electronic data systems. Comparison between the pre- and post-intervention group were analysed using paired t-test and McNemar test, with statistical significance p value of <0.05. RESULTS: A total of 25 medical officers used the toolkit on 60 CKD patients. The medical officers found the CKD-CHECK toolkit to be highly acceptable and feasible in primary care setting. The baseline characteristics of the patients were a mean age of 72 years old, predominantly females and Chinese ethnicity. Majority of the CKD patients had diabetes mellitus, hypertension and dyslipidemia. The numbers of CKD rapid progressors was similar (26.7% in the preintervention group vs 33.3% in the post-intervention group). There were no significant differences in terms of proteinuria assessment and ultrasound kidney for CKD rapid progressors before and after the intervention. However, a significant number of CKD rapid progressors were referred to nephrologists after the use of CKD-CHECK toolkit (p=0.016). CONCLUSIONS: CKD-CHECK toolkit is acceptable and feasible to be used in primary care. Preliminary findings show that the CKD-CHECK toolkit improved the primary care doctor's referral of rapid CKD progressors to nephrologists.

Are pelvic pain and increased pelvic floor muscle tone associated in women with persistent noncancer pelvic pain? A systematic review and meta-analysis.

BACKGROUND: The association between pelvic pain and pelvic floor muscle (PFM) tone in women with persistent noncancer pelvic pain (PNCPP) is unclear. AIM: To synthesize the evidence of the association between pelvic pain and PFM tone in women with PNCPP. METHODS: A systematic review was conducted via MEDLINE, Emcare, Embase, CINAHL, PsycINFO, and Scopus to identify relevant studies. Studies were eligible if pelvic pain and PFM tone outcome measures were reported among women aged >18 years. The National Heart, Lung, and Blood Institute's Quality Assessment Tool for Observational Cohort and Cross-sectional Studies was used to assess study quality. Studies were pooled by assessment of PFM tone via a random effects model. Associations between the presence of pelvic pain and PFM tone were assessed with odds ratio (OR), while linear associations were assessed with Pearson or Spearman correlation. OUTCOMES: Pelvic pain measures (intensity, threshold, and frequency) and resting PFM tone in women with PNCPP, as evaluated by any clinical assessment method or tool. RESULTS: Twenty-four studies were included in this review. The presence of pelvic pain was significantly associated with increased PFM tone as assessed by digital palpation (OR, 2.85; 95% CI, 1.66-4.89). Pelvic pain intensity was inversely but weakly associated with PFM flexibility when evaluated through dynamometry (r = -0.29; 95% CI, -0.42 to -0.17). However, no significant associations were found between pelvic pain and PFM tone when measured with other objective assessment methods. CLINICAL IMPLICATIONS: Pelvic pain and increased PFM tone may not be directly associated; alternatively, a nonlinear association may exist. A range of biopsychosocial factors may mediate or moderate the association, and clinicians may need to consider these factors when assessing women with PNCPP. STRENGTHS AND LIMITATIONS: This review was reported according to the PRISMA guidelines. All possible findings from relevant theses and conference abstracts were considered in our search. However, nonlinear associations between pelvic pain and increased PFM tone were not assessed as part of this review. CONCLUSION: Pelvic pain may be linearly associated with increased PFM tone and decreased PFM flexibility when measured with digital palpation or dynamometry; however, this association was not observed when other aspects of PFM tone were assessed through objective methods. Future studies are required using robust assessment methods to measure PFM tone and analyses that account for other biopsychosocial factors that may influence the association.

Vitamin D and smell impairment: a systematic literature review.

OBJECTIVE: Smell impairment affects 60-80 per cent of individuals aged over 80 years. This review aimed to identify any association between vitamin D deficiency and smell impairment, and determine the efficacy of vitamin D to treat smell impairment. METHODS: A literature search was conducted across four databases between the years 2000 and 2022. The literature screen was performed by two independent reviewers. RESULTS: Seven articles were included in this review. Four studies examined the association between vitamin D deficiency and smell impairment, with three studies identifying a significant relationship. Three studies investigated the use of vitamin D as treatment for smell impairment, which found complete resolution or significant symptom improvement after vitamin D deficiency was treated. CONCLUSION: This review identified limited studies on this topic. As vitamin D supplementation is relatively cost-efficient, further large-scale studies should be carried out to investigate the efficacy of vitamin D for treating anosmia.

A phase I study of an adenoviral vector delivering a MUC1/CD40-ligand fusion protein in patients with advanced adenocarcinoma.

Cancer vaccines as immunotherapy for solid tumours are currently in development with promising results. We report a phase 1 study of Ad-sig-hMUC1/ecdCD40L (NCT02140996), an adenoviral-vector vaccine encoding the tumour-associated antigen MUC1 linked to CD40 ligand, in patients with advanced adenocarcinoma. The primary objective of this study is safety and tolerability. We also study the immunome in vaccinated patients as a secondary outcome. This trial, while not designed to determine clinical efficacy, reports an exploratory endpoint of overall response rate. The study meets its pre-specified primary endpoint demonstrating safety and tolerability in a cohort of 21 patients with advanced adenocarcinomas (breast, lung and ovary). The maximal dose of the vaccine is 1 ×1011 viral particles, with no dose limiting toxicities. All drug related adverse events are of low grades, most commonly injection site reactions in 15 (71%) patients. Using exploratory high-dimensional analyses, we find both quantitative and relational changes in the cancer immunome after vaccination. Our data highlights the utility of high-dimensional analyses in understanding and predicting effective immunotherapy, underscoring the importance of immune competency in cancer prognosis.

POMMS: Pre-operative misoprostol in myomectomy surgery: A randomised controlled pilot study.

OBJECTIVE: To assess the effect of pre-operative sublingual misoprostol on intra-operative blood loss in abdominal myomectomy as compared to placebo. STUDY DESIGN: Double-blind randomised controlled pilot study. A single tertiary Gynaecology Unit in Melbourne, Australia. Women ≥ 18 years old undergoing laparoscopic or open myomectomy. Women undergoing laparoscopic or open myomectomy for symptomatic uterine leiomyomas were randomised to pre-operative sublingual 400mcg misoprostol or placebo. Intra-operative blood loss was measured via accurate record keeping of the post-operative volume in the suction canister and weighed packs, minus any irrigation fluid used. RESULTS: Intraoperative blood loss in the misoprostol treatment group was 306 ml ± 281 ml, compared to 325 ± 352 ml in the placebo group; P = 0.83. Fibroid volume was a consistent predictor of intra-operative blood loss. For each 1 ml increase in fibroid volume there is an increase in blood loss by 0.26 ml (95 % CI: 0.07 - 0.46). CONCLUSIONS: In this study, we found that there was no significant difference in blood loss between women who received and did not receive sublingual misoprostol before abdominal myomectomy. This is an exploratory study laying the foundation for further randomised clinical trials.

In vitro antiviral activity of medicinal mushroom Ganoderma neo-japonicum Imazeki against enteroviruses that caused hand, foot and mouth disease.

Hand, foot and mouth disease (HFMD) is a highly contagious viral disease that predominantly affects children younger than 5 years old. HFMD is primarily caused by enterovirus A71 (EVA71) and coxsackievirus A16 (CV-A16). However, coxsackievirus A10 (CV-A10) and coxsackievirus A6 (CV-A6) are being increasingly reported as the predominant causative of HFMD outbreaks worldwide since the past decade. To date, there are still no licensed multivalent vaccines or antiviral drugs targeting enteroviruses that cause HFMD, despite HFMD outbreaks are still being frequently reported, especially in Asia-Pacific countries. The high rate of transmission, morbidity and potential neurological complications of HFMD is indeed making the development of broad-spectrum antiviral drugs/agents against these enteroviruses a compelling need. In this study, we have investigated the in vitro antiviral effect of 4 Ganoderma neo-japonicum Imazeki (GNJI) crude extracts (S1-S4) against EV-A71, CV-A16, CV-A10 and CV-A6. GNJI is a medicinal mushroom that can be found growing saprophytically on decaying bamboo clumps in Malaysian forests. The antiviral effects of this medicinal mushroom were determined using cytopathic inhibition and virus titration assays. The S2 (1.25 mg/ml) hot aqueous extract demonstrated the highest broad-spectrum antiviral activity against all tested enteroviruses in human primary oral fibroblast cells. Replication of EV-A71, CV-A16 and CVA10 were effectively inhibited at 2 hours post-infection (hpi) to 72 hpi, except for CV-A6 which was only at 2 hpi. S2 also has virucidal activity against EV-A71. Polysaccharides isolated and purified from crude hot aqueous extract demonstrated similar antiviral activity as S2, suggesting that polysaccharides could be one of the active compounds responsible for the antiviral activity shown by S2. To our knowledge, this study demonstrates for the first time the ability of GNJI to inhibit enterovirus infection and replication. Thus, GNJI is potential to be further developed as an antiviral agent against enteroviruses that caused HFMD.

In vitro antiviral activity of medicinal mushroom Ganoderma neo-japonicum Imazeki against enteroviruses that caused hand, foot and mouth disease

@# Hand, foot and mouth disease (HFMD) is a highly contagious viral disease that predominantly affects children younger than 5 years old. HFMD is primarily caused by enterovirus A71 (EVA71) and coxsackievirus A16 (CV-A16). However, coxsackievirus A10 (CV-A10) and coxsackievirus A6 (CV-A6) are being increasingly reported as the predominant causative of HFMD outbreaks worldwide since the past decade. To date, there are still no licensed multivalent vaccines or antiviral drugs targeting enteroviruses that cause HFMD, despite HFMD outbreaks are still being frequently reported, especially in Asia-Pacific countries. The high rate of transmission, morbidity and potential neurological complications of HFMD is indeed making the development of broad-spectrum antiviral drugs/agents against these enteroviruses a compelling need. In this study, we have investigated the in vitro antiviral effect of 4 Ganoderma neo-japonicum Imazeki (GNJI) crude extracts (S1-S4) against EV-A71, CV-A16, CV-A10 and CV-A6. GNJI is a medicinal mushroom that can be found growing saprophytically on decaying bamboo clumps in Malaysian forests. The antiviral effects of this medicinal mushroom were determined using cytopathic inhibition and virus titration assays. The S2 (1.25 mg/ml) hot aqueous extract demonstrated the highest broad-spectrum antiviral activity against all tested enteroviruses in human primary oral fibroblast cells. Replication of EV-A71, CV-A16 and CVA10 were effectively inhibited at 2 hours post-infection (hpi) to 72 hpi, except for CV-A6 which was only at 2 hpi. S2 also has virucidal activity against EV-A71. Polysaccharides isolated and purified from crude hot aqueous extract demonstrated similar antiviral activity as S2, suggesting that polysaccharides could be one of the active compounds responsible for the antiviral activity shown by S2. To our knowledge, this study demonstrates for the first time the ability of GNJI to inhibit enterovirus infection and replication. Thus, GNJI is potential to be further developed as an antiviral agent against enteroviruses that caused HFMD.

Treatment of symptomatic fibroid disease using uterine fibroid embolisation: An Australian perspective.

Uterine leiomyomata (fibroids) are symptomatic in up to 35% of women and treatment can be a costly burden to the individual and society. Options for treatment range from non-hormonal, hormonal, minimally invasive, to surgery. While symptoms from smaller fibroids may respond to simple treatment, those with larger fibroids or with a large volume of disease require a more definitive option. Surgery (hysterectomy or myomectomy) are both well-established treatment modalities with good clinical outcomes. Since the 1990s, uterine fibroid embolisation has emerged as a less invasive option for women than for surgical techniques, while level 1 evidence shows that in the short to mid-term, there is a similar improvement in symptom-related quality of life outcomes to surgery, but with reduced hospital stay and reduced cost. However, in the longer term there may be a need for further treatment or retreatment in some patients compared with surgery. Since its introduction, uptake of this procedure in Australia has been low relative to surgical options. This manuscript reviews the current literature surrounding treatment, along with the trends in uptake of embolisation by Australian women, places this in context of current guidelines from major societies, and encourages gynaecologists and interventional radiologists to be aware of the advantages and limitations of embolisation.

Borrelia miyamotoi infection leads to cross-reactive antibodies to the C6 peptide in mice and men.

OBJECTIVES: Borrelia miyamotoi is a relapsing fever Borrelia, transmitted by hard (Ixodes) ticks, which are also the main vector for Borrelia burgdorferi. A widely used test for serodiagnosis of Lyme borreliosis is an enzyme immunoassay (EIA) based on the C6 peptide of the B. burgdorferi sl VlsE protein. We set out to study C6 reactivity upon infection with B. miyamotoi in a large well-characterized set of B. miyamotoi disease (BMD) patient sera and in experimental murine infection. METHODS: We performed in silico analyses, comparing the C6-peptide to immunodominant B. miyamotoi variable large proteins (Vlps). Next, we determined C6 reactivity in sera from mice infected with B. miyamotoi and in a unique longitudinal set of 191 sera from 46 BMD patients. RESULTS: In silico analyses revealed similarity of the C6 peptide to domains within B. miyamotoi Vlps. Cross-reactivity against the C6 peptide was confirmed in 21 out of 24 mice experimentally infected with B. miyamotoi. Moreover, 35 out of 46 BMD patients had a C6 EIA Lyme index higher than 1.1 (positive). Interestingly, 27 out of 37 patients with a C6 EIA Lyme index higher than 0.9 (equivocal) were negative when tested for specific B. burgdorferi sl antibodies using a commercially available immunoblot. CONCLUSIONS: We show that infection with B. miyamotoi leads to cross-reactive antibodies to the C6 peptide. Since BMD and Lyme borreliosis are found in the same geographical locations, caution should be used when relying solely on C6 reactivity testing. We propose that a positive C6 EIA with negative immunoblot, especially in patients with fever several weeks after a tick bite, warrants further testing for B. miyamotoi.

Commensal Candida albicans Positively Calibrates Systemic Th17 Immunological Responses.

Mucosal barriers are densely colonized by pathobiont microbes such as Candida albicans, capable of invasive disseminated infection. However, systemic infections occur infrequently in healthy individuals, suggesting that pathobiont commensalism may elicit host benefits. We show that intestinal colonization with C. albicans drives systemic expansion of fungal-specific Th17 CD4+ T cells and IL-17 responsiveness by circulating neutrophils, which synergistically protect against C. albicans invasive infection. Protection conferred by commensal C. albicans requires persistent fungal colonization and extends to other extracellular invasive pathogens such as Staphylococcus aureus. However, commensal C. albicans does not protect against intracellular influenza virus infection and exacerbates allergic airway inflammation susceptibility, indicating that positively calibrating systemic Th17 responses is not uniformly beneficial. Thus, systemic Th17 inflammation driven by CD4+ T cells responsive to tonic stimulation by commensal C. albicans improves host defense against extracellular pathogens, but with potentially harmful immunological consequences.

FRAX® based intervention thresholds for management of osteoporosis in Singaporean women.

Potential FRAX®-based major osteoporotic fracture (MOF) and hip fracture (HF) intervention thresholds (ITs) for postmenopausal Singaporean women were explored. Age-dependent ethnic-specific and weighted mean ITs progressively increased with increasing age. Fixed ITs were derived via discriminatory value analysis. MOF and HF ITs with highest the Youden index were chosen as optimal. INTRODUCTION: We aimed to explore FRAX®-based intervention thresholds (ITs) to potentially guide osteoporosis treatment in Singapore, a multi-ethnic nation. METHOD: One thousand and one Singaporean postmenopausal community-dwelling women belonging to Chinese, Malay and Indian ethnicities underwent clinical risk factor (CRF) and BMD assessment. FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) probabilities were calculated using ethnic-specific models. We employed the translational logic adopted by NOGG (UK), whereby osteoporosis treatment is recommended to any postmenopausal woman whose fracture probability based on other CRFs is similar to or exceeds that of an age-matched woman with a fracture. Using the same logic, ethnic-specific and mean weighted age-dependent ITs were computed. Employing these age-dependent ITs as a reference, the performance of fixed (age-independent) ITs were examined using ROC curves and discriminatory analysis, with the highest Youden index (YI) (sensitivity + specificity - 1) used to identify the optimal MOF and HF ITs. RESULTS: The mean age was 58.9 (6.9) years. Seven hundred and eighty-nine (79%) women were Chinese, 136 (13.5%) Indian and 76 (7.5%) Malay. Age-dependent MOF ITs ranged from 3.1 to 33%, 2.5 to 17% and 2.5 to 16% whilst HF ITs ranged from 0.7 to 17%, 0.4 to 6% and 0.4 to 6.3% in Chinese, Malay and Indian women, respectively, between the ages of 50 and 90 years. The weighted age-dependent MOF and HF ITs ranged from 2.9% and 0.6%, respectively, at the age of 50, to 28% and 14% at 90 years of age. Fixed MOF/HF ITs of 5.5%/1%, 2.5%/1% and 2.5%/0.25% were identified as the most optimal by the highest YI in Chinese, Malay and Indian women, respectively. Fixed MOFP and HF ITs of 4% and 1%, respectively, were found to be most optimal on the weighted means analysis. CONCLUSION: The ITs for osteoporosis treatment in Singapore show marked variations across ethnicities. Weighted mean thresholds may overcome the dilemma of intervening at different thresholds for different ethnicities. Choosing fixed ITs may have to involve trade-offs between sensitivity and specificity. FRAX®-based age-dependent or the fixed intervention thresholds suggested as an alternative to be considered for use in Singapore though further studies on the societal and health economic impacts of choosing these thresholds in Singapore are needed.

The bipedal saddle space: modelling and validation.

Better understanding of human balance control is pivotal for applications such as bipedal robots and medical technologies/therapies targeting human locomotion. Despite the inverted pendulum model being popular for describing bipedal locomotion, it does not properly capture the step-to-step transition dynamics. The major drawback has been the requirement for both feet to be on the ground which generates a discontinuity along the intersection of the potential energy surfaces produced by the two legs. To overcome this problem, we propose a generalized inverted pendulum-based model that can describe both single and double support phases. The full characterization of the system's potential energy allows the proposed model to drop the main limitation. This framework also enables optimal strategies to be designed for the transition between the two feet without the optimization algorithms. The proposed theory has been validated by comparing the human locomotor strategies output of our planner with real data from multiple experimental studies. The results show that our model generates trajectories consistent with human variability and performs better than existing well-known methods.

Necroptosis of infiltrated macrophages drives Yersinia pestis dispersal within buboes.

When draining lymph nodes become infected by Yersinia pestis (Y. pestis), a massive influx of phagocytic cells occurs, resulting in distended and necrotic structures known as buboes. The bubonic stage of the Y. pestis life cycle precedes septicemia, which is facilitated by trafficking of infected mononuclear phagocytes through these buboes. However, how Y. pestis convert these immunocytes recruited by host to contain the pathogen into vehicles for bacterial dispersal and the role of immune cell death in this context are unknown. We show that the lymphatic spread requires Yersinia outer protein J (YopJ), which triggers death of infected macrophages by downregulating a suppressor of receptor-interacting protein kinase 1-mediated (RIPK1-mediated) cell death programs. The YopJ-triggered cell death was identified as necroptotic, which released intracellular bacteria, allowing them to infect new neighboring cell targets. Dying macrophages also produced chemotactic sphingosine 1-phosphate, enhancing cell-to-cell contact, further promoting infection. This necroptosis-driven expansion of infected macrophages in buboes maximized the number of bacteria-bearing macrophages reaching secondary lymph nodes, leading to sepsis. In support, necrostatins confined bacteria within macrophages and protected mice from lethal infection. These findings define necrotization of buboes as a mechanism for bacterial spread and a potential target for therapeutic intervention.

Intramural Ectopic Pregnancy Following Myomectomy.

Intramural pregnancy is a rare form of ectopic pregnancy with early diagnosis essential for prevention of severe hemorrhage and uterine rupture. We report a rare case of an intramural ectopic pregnancy at 12 weeks gestation in a woman 1 year post open myomectomy. Both transvaginal ultrasound and magnetic resonance imaging were utilized as diagnostic aids in this case. The rare nature of this clinical scenario and lack of guidelines for management made clinical decision making difficult. Due to the size and location of the gestational sac, hysterectomy was deemed to be the safest modality, and a midline laparotomy, total abdominal hysterectomy, and bilateral salpingectomy was performed.

Serodiagnosis of Borrelia miyamotoi disease by measuring antibodies against GlpQ and variable major proteins.

OBJECTIVES: Borrelia miyamotoi disease (BMD) is an emerging tick-borne disease in the Northern hemisphere. Serodiagnosis by measuring antibodies against glycerophosphodiester-phosphodiesterase (GlpQ) has been performed experimentally but has not been extensively clinically validated. Because we had previously shown the differential expression of antigenic variable major proteins (Vmps) in B. miyamotoi, our aim was to study antibody responses against GlpQ and Vmps in PCR-proven BMD patients and controls. METHODS: We assessed seroreactivity against GlpQ and four Vmps in a well-described, longitudinal cohort of sera from BMD patients (n=182), healthy blood donors (n=136) and controls (n=68). All samples were tested by ELISA and positive sera were tested by western blot, and antibody dynamics and diagnostic value were assessed. RESULTS: IgM antibodies against GlpQ and Vmps peaked between 11 and 20 days, and IgG between 21 and 50 days, after disease onset. Various combinations of GlpQ and Vmps increased sensitivity and/or specificity compared to single antigens. Notably, the GlpQ or variable large protein (Vlp)-15/16 combination yielded a sensitivity of 94.7% (95% CI: 75.4-99.7) 11-20 days after disease onset and a specificity of 96.6% (92.7-98.4) for IgM. A specificity of 100% (97.8-100) for IgM, and 98.3% for IgG (95.2-100), was found when positivity was defined as reactivity to GlpQ and any Vmp, with maximum sensitivities of 79% (56.7-91.5) for IgM and 86.7% (62.1-97.6) for IgG. CONCLUSIONS: We clearly demonstrate here the diagnostic potential of these seromarkers. Our findings will facilitate future epidemiological and clinical studies on BMD and lead to the development of a serologic test to be used in clinical practice.

Comparison of management regimens following ultrasound diagnosis of nontubal ectopic pregnancies: a retrospective cohort study.

OBJECTIVE: To review management options for nontubal ectopic pregnancies. DESIGN: Retrospective cohort study. SETTING: Tertiary hospital in Melbourne, Australia. POPULATION: A total of 100 nontubal pregnancies: 1 abdominal, 32 caesarean scar, 14 cervical, 41 cornual-interstitial, 12 ovarian. METHODS: Cases were classified according to ectopic site. Management categories were medical, surgical, combination or expectant. Use of minimally invasive approaches (ultrasound-guided intra-sac injections or selective surgical techniques) was identified. Primary management was considered to be successful if no further unplanned interventions were required. MAIN OUTCOME MEASURES: Success of primary management and frequency of unplanned interventions. RESULTS: A high rate of success (82%) was demonstrated for all management regimens, with minimal morbidity and no deaths occurring. A high success rate was shown when the primary management regimen was systemic methotrexate or ultrasound-guided intra-sac injection (88%). The success rate for primary surgical management was 57%. High success rates were reported for both primary management with ultrasound-guided injections or in combination with systemic methotrexate (94%) and for primary management with systemic methotrexate alone (81%). Seventy-five per cent of women managed with minimally invasive surgical approaches avoided the need for more extensive surgery, but required longer follow up and additional interventions. CONCLUSION: Minimally invasive approaches were found to be safe and effective treatment for women desiring to conserve fertility. Ultrasound-guided intra-sac injection and laparoscopic ectopic removal procedures aimed at preserving reproductive organs should be included as minimally invasive primary management tools in addition to the well-recognised option of systemic methotrexate. TWEETABLE ABSTRACT: Nontubal ectopics: minimally invasive procedures a safe alternative to surgery in selected cases.

Commensal Fungi Recapitulate the Protective Benefits of Intestinal Bacteria.

Commensal intestinal microbes are collectively beneficial in preventing local tissue injury and augmenting systemic antimicrobial immunity. However, given the near-exclusive focus on bacterial species in establishing these protective benefits, the contributions of other types of commensal microbes remain poorly defined. Here, we show that commensal fungi can functionally replace intestinal bacteria by conferring protection against injury to mucosal tissues and positively calibrating the responsiveness of circulating immune cells. Susceptibility to colitis and influenza A virus infection occurring upon commensal bacteria eradication is efficiently overturned by mono-colonization with either Candida albicans or Saccharomyces cerevisiae. The protective benefits of commensal fungi are mediated by mannans, a highly conserved component of fungal cell walls, since intestinal stimulation with this moiety alone overrides disease susceptibility in mice depleted of commensal bacteria. Thus, commensal enteric fungi safeguard local and systemic immunity by providing tonic microbial stimulation that can functionally replace intestinal bacteria.