Acute Cerebillitis Due to Salmonella typhimurium Infection in an Adult: A Report of an Unusual Case.

Acute cerebellitis is an inflammatory illness that may manifest as a primary, para-infectious, or post-infectious disease. The clinical manifestations of acute cerebellitis are traditionally characterized by fever, vomiting, headache, and altered sensorium, accompanied by impaired cerebellar function corroborated by neuroradiography alterations. Acute cerebellitis may lead to a potentially fatal increase in pressure within the skull, requiring immediate and critical neurosurgical surgery. It is important to note that cerebellar symptoms may not be evident initially. This report provides a comprehensive analysis of a case of a 57-year-old male patient who had been diagnosed with acute cerebellitis caused by an infection with Salmonella typhimurium.

Limiting Factors in Implementing Pharmacovigilance Principles in the Elderly.

The overarching aim of pharmacovigilance is to ensure the safe and effective usage of medication across the population and optimise medicines through holistic considerations. However, within the heterogeneous elderly population, several unique factors are at play, limiting the ability of clinicians to fulfil this aim. A matured physiology influencing the response and effects of drugs, increased polypharmacy enabling drug-drug interactions, and greater consumption of concurrent herbal medicines predispose patients to harmful drug events. This increasingly multimorbid subpopulation requires complex pharmaceutical regimens encouraging inappropriate prescribing and medicine non-adherence leading to suboptimal therapy. Furthermore, restrictive practices in clinical trials commonly exclude elderly patients creating disparities from expected findings within a real-world setting. These issues create an environment where elderly patients are at a heightened risk of adverse drug events and clinicians are forced to make significant decisions from limited information. With projections showing that this demographic will continue growing in size, the true burden of these limiting factors is yet to be realised.

Outcome measures reported following feminizing genital gender affirmation surgery for transgender women and gender diverse individuals: A systematic review.

Background: Feminizing genital gender affirmation surgery (fgGAS) may be an essential adjunct in the care of some transgender women and gender diverse individuals with gender incongruence. However, the comparison of different techniques of fgGAS may be confounded by variable outcome reporting and the use of inconsistent outcomes in the literature. This systematic review provides the most in-depth examination of fgGAS studies to date, and summarizes all reported outcomes, definitions, and the times when outcomes were assessed following these surgical interventions. Aims/Methods: This work intends to quantify the levels of outcome variability and definition heterogeneity in this expanding field and provides guidance on outcome reporting for future study authors. Candidate studies for this systematic review were sourced via an electronic, multi-database literature search. All primary, clinical research studies of fgGAS were included with no date limits. Paired collaborators screened each study for inclusion and performed data extraction to document the outcomes, definitions, and times of outcome assessment following fgGAS. Results: After screening 1225 studies, 93 studies proceeded to data extraction, representing 7681 patients. 2621 separate individual outcomes were reported, 857 (32.7%) were defined, and the time of outcome assessment was given for 1856 outcomes (70.8%) but relied on nonspecific ranges of follow-up dates. "Attainment of orgasm", "Neovaginal stenosis", and "Neovaginal depth/length" were among the most commonly reported outcomes. Profound heterogeneity existed in the definitions used for these and for all outcomes reported in general. Discussion: The results demonstrate a need for clear outcomes, agreed definitions, and times of outcome assessment following fgGAS in transgender women and gender diverse individuals. The adoption of a consistent set of outcomes and definitions reported by all future studies of fgGAS (a Core Outcome Set) will aid in improving treatment comparisons in this patient group. This review is the first step in that process.

Clinical significance of Notch receptors in triple negative breast cancer.

BACKGROUND: The Notch signaling pathway is an evolutionary conserved cell signaling pathway that plays an indispensable role in essential developmental processes. Aberrant activation of Notch pathway is known to initiate wide array of diseases and cancers. OBJECTIVE: To evaluate the clinical significance of Notch receptors in Triple Negative Breast Cancer. METHODS: We evaluated the association between Notch receptors and clinicopathological parameters including disease-free survival and overall survival of one hundred TNBC patients by immunohistochemistry. RESULTS: Positive expression of nuclear Notch1 receptor (18%) was found be significantly correlated with positive lymph node (p = 0.009), high BR score (p = 0.02) and necrosis (p = 0.004) while cytoplasmic expression of Notch2 receptor (26%) was significantly correlated with metastasis (p = 0.05), worse DFS (p = 0.05) and poor OS (p = 0.02) in TNBC patients. Membrane (18%) and cytonuclear (3%) Notch3 expression were significantly associated with poorly differentiated tumors (p = 0.007), high BR score (p = 0.002) and necrosis (p = 0.03) respectively. However, cytoplasmic Notch3 and Notch4 expression were negatively correlated with poor prognostic factors. CONCLUSIONS: Our data indicated that Notch receptors play a key role in promoting TNBC and mainly, Notch2 may contribute to poor prognosis of the disease. Hence, it is implicated that Notch2 may serve as a potential biomarker and therapeutic target for TNBC.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): Prevalence, clinicopathological characteristics and survival outcome in a cohort of 311 patients with well-differentiated lung neuroendocrine tumours.

INTRODUCTION: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is considered to be a rare condition associated with lung neuroendocrine tumours (NET), and its natural history is poorly described. We aimed to assess the prevalence and clinicopathologic characteristics of DIPNECH in the lung NET population, and to investigate predictors of time-to-progression (TTP) and overall survival (OS). METHODS: We retrospectively identified patients diagnosed with DIPNECH between April 2005 and December 2020. Clinical data were collected from medical records. The relationship between baseline characteristics and TTP and OS was analysed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazards model. RESULTS: Of 311 patients with well-differentiated lung NETs, 61 (20%) had DIPNECH and were included in the study. Baseline demographics described 95% female, 59% never smokers and mean body mass index 34.4 kg m-2 ; 77% were typical carcinoids (TC), 13% atypical carcinoids (AC), and 10% both TC and AC (multicentric). At presentation, 54% of patients were asymptomatic. Multicentric NETs were demonstrated in 16 (26%) on histopathology, and a further 32 (52%) had synchronous NETs suggested on imaging (multiple nodules ≥ 5 mm). Seven (11%) patients developed metastases and the median OS from time of first metastasis was 37 months. AC histopathology and NET TNM stage ≥ IIA were associated with poorer TTP and OS. Of the DIPNECH cohort, the 15-year survival rate was 86%. CONCLUSIONS: DIPNECH may be more prevalent in the lung NET population than previously appreciated, especially in women. Although our results confirm that DIPNECH is predominantly an indolent disease associated with TC, 23% developed AC and these patients may warrant closer observation.

Negative Appendicectomy Rate: Incidence and Predictors.

Introduction Acute appendicitis is a common emergency surgical presentation. The gold standard treatment is surgery. Like any surgical procedure, appendicectomy is associated with complications. Negative appendicectomy (NA) can occur, and its incidence is 15%-39%. This study aimed to evaluate the rate and predictors of NA in a cohort. Patients and methods A retrospective study over a year through which data of patients who underwent emergency appendicectomies were collected and analyzed. The absence of inflammatory process and/or other significant pathology in the appendix was considered negative for appendicitis. An utter definition of NA was the absence of inflammatory cells in the appendix. The NA rate (NAR) was calculated using the standard criteria (NAR-SDC) and the strict criteria (NAR-STC). The routine laboratory parameters for diagnosing acute appendicitis on admission were collected. Increased inflammatory markers in the form of leucocytosis of total WBC > 11,000 per mm, elevated CPR > 5 mg/L, and isolated elevated total serum bilirubin > 20 µmol/L, were suggestive of acute appendicitis. Results Three hundred and seventy-two patients were included, 179 males and 193 females with a median age were 27 (5-94) years. The median duration of symptoms and waiting time to surgery were two days and one day, respectively. The mean admission WBC, C-reactive protein (CRP) and serum bilirubin levels were 12,600 (3,000-38,000)/mm3, 66.9 (1-323) mg/L and 12.7 (4-38) µmol/L respectively. Laparoscopic appendicectomy was performed in 93.5% of patients with a conversion rate of 4.6%. NAR-SDC was 10.2% and NAR-STC was 25.8%. NAR was significantly higher in females than males (39.4% versus 11.1%; p-value 0.0001). Patients with NA were younger (p-value 0.0001), had lower mean total WBC (p-value 0.014), CRP (p-value 0.0001) and total serum bilirubin (p-value 0.0001) levels on admission. Conclusion NA is still a major problem in the management of patients with acute right lower abdominal pain. Our NAR compared favourably with reported rates. Female gender, duration of symptoms more than three days, and lower total WBC were independent predictors of NA.

Pulmonary Function Tests as a Biomarker in Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia Patients Treated With Somatostatin Analogues.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) describes an indolent, under-recognised and poorly understood pulmonary condition with fewer than 200 reported cases across the literature. Currently, cases are diagnosed following a biopsy of the primary lesion, with treatment options centring on symptomatic benefit as opposed to targeting the underlying aetiology. Classically, DIPNECH lesions have been described as slow growing and benign, but with growing awareness of the condition, reports of metastatic disease with significant symptomatic burden have been reported. However, effectively addressing the subset of DIPNECH patients with greater metastatic potential remains an unmet clinical need. Due to the similarities between DIPNECH and carcinoid patients, several centres have considered using somatostatin analogues to not only help symptomatically but also to initiate tumour regression. However, to date, there are limited biomarkers to help evaluate the benefit of such options. In this review, we consider the use of pulmonary function tests (PFTs) to help quantify the benefit of somatostatin analogues. Although much of the evidence stems from small single-centre studies, the use of PFTs within the treatment pathway for both localised and metastatic DIPNECH represents a meaningful improvement from subjective monitoring of disease.

Use of Wide-Awake Local Anaesthetic No Tourniquet (WALANT) in upper limb and hand surgery: A systematic review protocol.

INTRODUCTION: Wide Awake Local Anaesthetic No Tourniquet (WALANT) technique has been developed to eliminate tourniquet pain during upper limb and hand surgery whilst also improving utilisation of operating theatre time and inpatient stay, however inconclusive data still limits the techniques uptake. Here presents a protocol for a systematic review to collate findings to produce conclusive data on efficacy of WALANT. METHODS: This systematic review will be registered a priori. All study designs defined by the Oxford Centre for Evidence-Based Medicine will be included in the search. "WALANT" in "upper limb" and "hand" surgery will be investigated as per the devised search strategy. 18 electronic databases will be searched, including PubMed, Medline and Embase in addition to a Grey literature search. Two independent teams of 3 researchers will screen all relevant titles, abstracts and subsequent full texts for suitability. Data will be extrapolated and entered into a preformatted database for analysis. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal and presented at both national and international conferences within the field of plastic and orthopaedic surgery. This review aims to inform surgical practice and policy.

Predictors of antiproliferative effect of lanreotide autogel in advanced gastroenteropancreatic neuroendocrine neoplasms.

PURPOSE: The antiproliferative properties of lanreotide autogel (LAN) in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) were demonstrated in the CLARINET study. However, there is limited literature regarding factors that affect progression-free survival (PFS) in patients with GEP NENs treated with LAN. METHODS: We identified a total of 191 treatment-naive patients with advanced GEP NENs and positive SSTR uptake on imaging (Octreoscan or 68Gallium DOTATATE Positron Emission Tomography [68GaPET]) who received first-line LAN monotherapy, albeit at various starting doses (60, 90 or 120 mg/month). A group of 102 patients who initiated treatment at the standard dose of 120 mg/month were included in the study and further evaluated by univariate and multivariate analyses to identify predictors of PFS. RESULTS: The location of tumour primary was in the small bowel in 63 (62%), pancreas in 31 (30%) and colon/rectum in 8 patients (8%). The tumours were well-differentiated, and the majority were grade 1 (52%), or 2 (38%). About 60% of cases had progressive disease at the time of treatment initiation. Most patients with available pretreatment nuclear medicine imaging (Octreoscan or 68Ga PET) had a Krenning score of 3 (44%) or 4 (50%). The median PFS for the entire cohort was 19 months (95% CI 12, 26 months). The univariate analysis demonstrated that grade 2 tumours, progressive disease at baseline and metastatic liver disease were associated with a significantly shorter PFS, while other evaluated variables did not affect PFS at a statistically significant level. However, at multivariate analysis only the tumour grade remained statistically significant. CONCLUSIONS: The current study showed that, of many evaluated variables, only the tumour grade was predictive of PFS duration and this should be considered during patient selection for treatment.