The immune cell profile of human fallopian tubes in health and benign pathology: a systematic review.

The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for implantation. Histologically, the FT mucosa consists of three main cell types: secretory, ciliated and peg cells. In addition, several studies have reported the presence of immune cells. This systematic review aims to present a comprehensive analysis of the immune cell populations in the human FT, both in health and benign pathology, to promote a better understanding of tubal pathologies and their influence on infertility. A comprehensive literature search was conducted across five databases and augmented with manual citation chaining. Forty-two eligible studies were selected in accordance with PRISMA guidelines. Following screening, risk of bias assessments were conducted, data extracted and the findings presented thematically. T lymphocytes, predominantly CD8+ T cells, represent the most abundant immune cell population within the healthy FT, with B lymphocytes, macrophages, NK cells and dendritic cells also localised to the tubal mucosa. There is evidence to suggest that lymphocyte and macrophage populations are susceptible to changes in the concentration of reproductive hormones. Tubal ectopic pregnancy, salpingitis, hydrosalpinx and endometriosis are all characterised by an increased population of macrophages in comparison to healthy FT. However, given the inconsistent evidence presented between studies, and the lack of studies examining all immune cell subtypes in tubal pathologies, only limited conclusions can be formulated on pathology-specific immune cell populations, and further research is required for validation.

Completion Total Mesorectal Excision After Transanal Local Excision of Early Rectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Completion total mesorectal excision is recommended when local excision of early rectal cancers demonstrates high-risk histopathological features. Concerns regarding the quality of completion resections and the impact on oncological safety remain unanswered. OBJECTIVE: This study aims to summarize and analyze the outcomes associated with completion surgery and undertake a comparative analysis with primary rectal resections. DATA SOURCES: Data sources included PubMed, Cochrane library, MEDLINE, and Embase databases up to April 2021. STUDY SELECTION: All studies reporting any outcome of completion surgery after transanal local excision of an early rectal cancer were selected. Case reports, studies of benign lesions, and studies using flexible endoscopic techniques were not included. INTERVENTION: The intervention was completion total mesorectal excision after transanal local excision of early rectal cancers. MAIN OUTCOME MEASURES: Primary outcome measures included histopathological and long-term oncological outcomes of completion total mesorectal excision. Secondary outcome measures included short-term perioperative outcomes. RESULTS: Twenty-three studies including 646 patients met the eligibility criteria, and 8 studies were included in the meta-analyses. Patients undergoing completion surgery have longer operative times (standardized mean difference, 0.49; 95% CI, 0.23-0.75; p = 0.0002) and higher intraoperative blood loss (standardized mean difference, 0.25; 95% CI, 0.01-0.5; p = 0.04) compared with primary resections, but perioperative morbidity is comparable (risk ratio, 1.26; 95% CI, 0.98-1.62; p = 0.08). Completion surgery is associated with higher rates of incomplete mesorectal specimens (risk ratio, 3.06; 95% CI, 1.41-6.62; p = 0.005) and lower lymph node yields (standardized mean difference, -0.26; 95% CI, -0.47 to 0.06; p = 0.01). Comparative analysis on long-term outcomes is limited, but no evidence of inferior recurrence or survival rates is found. LIMITATIONS: Only small retrospective cohort and case-control studies are published on this topic, with considerable heterogeneity limiting the effectiveness of meta-analysis. CONCLUSIONS: This review provides the strongest evidence to date that completion surgery is associated with an inferior histopathological grade of the mesorectum and finds insufficient long-term results to satisfy concerns regarding oncological safety. International collaborative research is required to demonstrate noninferiority. REGISTRATION NO: CRD42021245101.

Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea.

Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40-50-dB increase in thresholds for frequencies 8-32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC.

What has happened to antimicrobial usage in primary care in the United Kingdom since the SMAC report? - description of trends in antimicrobial usage using the General Practice Research Database.

BACKGROUND: The aim of the study was to assess antibiotic prescribing within the United Kingdom for three of the Standing Medical Advisory Committee recommendations 'four things which could be done'. METHODS: We conducted a retrospective survey of morbidity and antibiotic prescribing data between 1993 and 2001 using the national General Practice Research Database. Antibiotic prescribing was linked to diagnoses of cough/cold and sore throat; length of antibiotic course for uncomplicated cystitis. RESULTS: The rate of antibiotic prescribing for cough/cold declined between 1993 (43.7 per 1000 patient years at risk) and 1999 (23.5 per 1000 patient years at risk) and has since increased slightly (to 30.5 per 1000 patient years at risk in 2001). Antibiotic prescribing for sore throat declined between 1995 (80.6 per 1000 patient years at risk) and 1999 and has since remained static (42.1 per 1000 patient years at risk in 2001). Trimethoprim was the most commonly used antibiotic for episodes of uncomplicated cystitis and the prescription of 3 day (or less) courses has increased from 16.4 per cent in 1998 to 41.5 per cent in 2001. CONCLUSIONS: For the SMAC recommendation to limit prescribing for uncomplicated cystitis to 3 days in otherwise fit women there has been demonstrable impact since the publication of the SMAC report. For two recommendations (no prescribing of antibiotics for simple coughs and colds; no prescribing of antibiotics for viral sore throats) the impact has been less clear against the background of a general reduction in antimicrobial prescribing.