Two-year outcomes of conservatively managed appendicitis during the COVID-19 pandemic-a multicentre cohort study.

PURPOSE: During the COVID-19 pandemic, the new RCSEng guidelines resulted in appendicitis being more commonly managed conservatively to avoid aerosol-generating procedures. This resulted in shorter hospital stays without increased short-term complications. The 2-year outcomes of this change, specifically recurrence and re-admission rates remain unknown. METHODS: We conducted a multicentre, prospective, observational study including all adult patients treated as appendicitis after the implementation of the new surgical guidelines during the COVID-19 pandemic. Outcomes included initial management failure, re-admission rate, appendicitis recurrence, and interval appendicectomy. A historical cohort prior to the COVID-19 pandemic was used for comparison. Patients were followed up for 2-years post index admission. Categorical and continuous variables were compared using Fisher's exact test and Student's T or Mann-Whitney U tests as appropriate. RESULTS: Sixty-three and 79 patients with appendicitis were included from four NHS trusts, before (A) and after (B) the new intercollegiate guidelines respectively. Operative management was used less frequently in cohort B (28/79 vs 52/63; p<0.001). More patients re-presented in cohort B (14/79 vs 3/63; p=0.020), but not when comparing only those managed conservatively (2/11 vs 13/52; p=1.000). A similar trend was observed for appendicitis recurrence although without statistical significance (2/63 vs 9/79; p=0.112); with loss of trend when comparing those managed conservatively-only (2/11 vs 9/52; p=1.000). Among all patients, four (2.8%) were found to have underlying neoplasia of which three were initially managed conservatively (3/63; 4.8%). CONCLUSION: Conservative management of appendicitis has previously been shown to have short-term benefits in expedited hospital discharge without early complications. The present study shows it has a higher readmission and appendicitis recurrence rates. The risks of this alongside missed/delayed management of neoplasia needs to be considered alongside the benefits including avoidance of aerosol-generating general anaesthesia and laparoscopy during the COVID-19 pandemic or similar future health crises. Small case numbers limit analysis.

Suprascapular nerve blockage for painful shoulder pathology - a systematic review and meta-analysis of treatment techniques.

BACKGROUND: Suprascapular nerve blockade (SSNB) through injection (SSNBi) and/or pulsed radiofrequency (PRF) provide options for the management of painful shoulder pathology. Multiple techniques for delivery of SSNB are described but no consensus on optimal symptom control is available. This systematic review and meta-analysis aims to assess patient-focussed outcomes in SSNB and explore the impact of variation in the technical application of this treatment modality. METHODS: MEDLINE, Embase and CINAHL were searched for case series, cohort studies and randomised control trials published from database inception until 28 January 2021. Articles reporting use of SSNBi or PRF for treatment of shoulder pain with a minimum 3 months follow-up were included. Patient-reported outcome measures (PROMs) were extracted and the pooled standardised mean difference (SMD), weighted by study size, was reported. Quality of methodology was assessed using Wylde's nonsummative four-point system. FINDINGS: Of 758 references, 18 studies were included, totalling 704 SSNB. Average pain improvement at 3 months was 52.3%, with meta-analysis demonstrating a SMD of 2.37. Whereas SSNBi combined with PRF shows the greatest SMD of 2.75, this did not differ significantly from SSNBi or PRF when used as monotherapy. Location of treatment and the guidance technique used did not influence outcome. CONCLUSION: SSNBi and PRF provide safe and effective treatment for shoulder pain, as judged by PROMs. This may be of particular value in aging or comorbid patients and with surgical restrictions during the COVID-19 pandemic. Regardless of technique, patients experience a marked improvement in pain that is maintained beyond 3 months.

Suspected appendicitis and COVID-19, a change in investigation and management-a multicentre cohort study.

PURPOSE: The COVID-19 pandemic has reformed global healthcare delivery. On 25 March 2020, Intercollegiate guidelines were published in the UK to promote safe surgical provision during the COVID-19 outbreak advocating non-operative management or avoidance of laparoscopy when surgery is essential. The effects of this on the investigation and management of appendicitis remain unknown. METHODS: We performed a multicentre, prospective, observational study from the start of the new guidelines to the 6th of May 2020. We included all patients referred to surgical teams with suspected appendicitis. A recent historical cohort was identified for comparison. The primary outcome was the impact of the COVID-19 pandemic on the use of non-operative management in appendicitis. Secondary outcomes included imaging, negative appendicectomy rate (NAR), length of stay (LOS) and 30-day complications. RESULTS: A total of 63/164 (38%) patients compared to 79/191 (41%) were diagnosed with appendicitis before and after the guidelines were introduced (p = 0.589). CT scanning increased (71/164 vs 105/191; p = 0.033) while ultrasound scanning decreased (71/164 vs 62/191; p = 0.037). Appendicitis was more likely to be managed non-operatively (11/63 vs 51/79; p < 0.001) and, of those managed surgically, with an open approach (3/52 vs 26/28 p < 0.001). The NAR also reduced (5/52 vs 0/28; p = 0.157). LOS was shorter in non-operatively managed patients (1 day vs 3 days; p < 0.001) without a difference in complications (10/51 vs 4/28; p = 0.760). CONCLUSION: Introduction of the guidelines was associated with changes in practice. Despite these changes, short-term complications did not increase and LOS decreased. Questions remain on the longer-term complication rates in non-operatively managed patients.

Brucellosis-induced autoimmune haemolytic anaemia (AIHA).

Brucellosis is a rare zoonotic infection caused by small, fastidious Gram-negative coccobacilli of the genus Brucella that may be associated with haemolytic complications including thrombotic microangiopathy and haemolytic anaemia. We describe a patient with culture confirmed brucellosis who presented with malaise, high grade fever, hepatosplenomegaly and Coombs-positive autoimmune haemolytic anaemia. The patient was successfully treated with combination of doxycycline and rifampicin with no further episodes of relapses or haemolysis. Although rare, the possibility of brucellosis should always be kept in mind in patients with risk factors who present with haemolysis and endemic area.

Geometric Flow Control Lateral Flow Immunoassay Devices (GFC-LFIDs): A New Dimension to Enhance Analytical Performance.

The nitrocellulose (NC) membrane based lateral flow immunoassay device (LFID) is one of the most important and widely used biosensor platforms for point-of-care (PoC) diagnostics. However, the analytical performance of LFID has limitations and its optimization is restricted to the bioassay chemistry, the membrane porosity, and the choice of biolabel system. These bottom neck technical issues resulted from the fact that the conventional LFID design principle has not evolved for many years, which limited the LFID for advanced biosensor applications. Here we introduce a new dimension for LFID design and optimization based on geometric flow control (GFC) of NC membranes, leading to highly sensitive GFC-LFID. This novel approach enables comprehensive flow control via different membrane geometric features such as the width (w) and the length (l) of a constriction, as well as its input angle (θ 1) and output angle (θ 2). The GFC-LFID (w=0.5 mm, l=7 mm, θ 1 = 60°, θ 2 = 45°) attained a 10-fold increase in sensitivity for detection of interleukin-6 (IL-6), compared with conventional LFID, whereas reducing by 10-fold the antibody consumption. The GFC-LFID detects IL-6 over a linear range of 0.1-10 ng/mL with a limit of detection (LoD) of 29 pg/mL, which even outperforms some commercial IL-6 LFIDs. Such significant improvement is attained by pure geometric control of the NC membrane, without additives, that only relaying on a simple high throughput laser ablation procedure suitable for integration on regular large-scale manufacturing of GFC-LFIDs. Our new development on GFC-LFID with the combination of facile scalable fabrication process, tailored flow control, improved analytical performance, and reduced antibodies consumption is likely to have a significant impact on new design concept for the LFID industry.

Outcomes of upper extremity versus lower extremity placed peripherally inserted central catheters in a medical-surgical neonatal intensive care unit1.

OBJECTIVE: To compare outcomes of peripherally inserted central catheters (PICCs) placed in the upper extremity (UE) versus the lower extremity (LE) in a quaternary medical-surgical neonatal intensive care unit (NICU). RESULTS: We analyzed a total of 365 PICCs of which 250 (68%) were removed for end of therapy and 115 (32%) were removed due to complications. Patients who had UE insertions compared to LE insertions were of lower gestational age (median (IQR)), 30 (26, 35) vs. 32 (27, 37) weeks respectively (p = 0.014). UE PICCs were more likely to be removed due to complications compared to LE PICCs (39.9% vs. 26.4%, RR 1.51, 95% CI 1.12 -2.03, p = 0.007). UE PICCs were more likely than LE PICCs to be removed for the complications of malposition, dislodgement, and pleural or pericardial effusions; while LE PICCs were more likely to be removed for phlebitis. There were no differences in the rates of sepsis at 13.0% vs. 12.8% for UE vs. LE respectively, or causal organisms for sepsis. Survival analysis demonstrated that LE PICCs had a longer time to removal for a complication (p = 0.031). CONCLUSIONS: LE compared with UE PICCs were not associated with worse outcomes in a medical-surgical neonatal population that included a significant proportion of full-term neonates, and provide a valuable alternate site for central venous access. Increased awareness of the types of complications for UE compared with LE PICCs may help focus preventive and surveillance efforts based on PICC location, to improve safety and minimize the complications of NICU PICCs.

Severe hypothyroidism presenting with supraventricular tachycardia.

Thyroid disease is common and can have various systemic manifestations including cardiac diseases. Hypothyroidism is commonly associated with sinus bradycardia, low QRS complexes, prolonged QT interval and conduction blocks but rarely may cause arrhythmias. We present a patient who presented with presyncope and supraventricular tachycardia with severe hypothyroidism. Patient responded well to thyroxine replacement with biochemical improvement, the disappearance of arrhythmia after restoration of euthyroidism suggests that hypothyroidism might be the cause of supraventricular tachycardia. The aim of this report is to underline the possible aetiological link between supraventricular tachycardia and hypothyroidism, although supraventricular arrhythmias are ordinary features of hyperthyroidism.

Sinonasal inverted papilloma recurrence rates and evaluation of current staging systems.

BACKGROUND: Sinonasal inverted papillomas (SNIPs) are benign epithelial growths with high recurrence rates after surgical management. This study aims to evaluate SNIP recurrence rates after endoscopic surgery and to provide a comparison of published staging systems. METHODS: This chart review evaluated primary and revision SNIP cases from January 2008 to December 2016 at a tertiary sinus centre. Data was collected on patient demographics, origin site, surgical approaches, follow-up duration, recurrence, and smoking history. Each case was staged using Krouse, Oikawa, Cannady, Han, and Kamel systems. RESULTS: 52 primary and 22 revision SNIP patients had a mean follow-up of 42.3 (range:3-55) months. 11 primary cases (21.1%) and 5 revision cases (22.7%) had recurrences. Primary and revision cases had a mean time to recurrence of 24.0 (range:3-55) and 14.6 (range:10-20) months respectively. Smoking history had an OR of 0.63 (CI 95%: 0.18-2.22) for recurrence. The age group of 20-39 years featured the highest rates of recurrence. Patient groups defined by each staging system were compared by Kaplan-Meier survival analyses and logrank tests. Chi-squared values for Krouse, Oikawa, Cannady, Han, and Kamel systems were 6.73, 7.02, 6.19, 8.23 and 3.29, respectively. CONCLUSION: Recurrence rates found in this study are comparable to published literature. No statistical significance was found to associate smoking with recurrence. Han and Cannady staging systems were found to define patient groups that correlated well with recurrence. Staging systems should play a role in the management of SNIPs, especially to identify patients requiring additional post-surgical monitoring.

Correction: W.C. Mak, et al. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules. J. Funct. Biomater. 2015, 6, 439-453.

Recently, we found a mistake in Figure 4D in our previously published paper[...].

Integrating printed microfluidics with silicon photomultipliers for miniaturised and highly sensitive ATP bioluminescence detection.

Bioluminescence has been widely used for important biosensing applications such as the measurement of adenosine triphosphate (ATP), the energy unit in biological systems and an indicator of vital processes. The current technology for detection is mainly based on large equipment such as readers and imaging systems, which require intensive and time-consuming procedures. A miniaturised bioluminescence sensing system, which would allow sensitive and continuous monitoring of ATP, with an integrated and low-cost disposable microfluidic chamber for handling of biological samples, is highly desirable. Here, we report the design, fabrication and testing of 3D printed microfluidics chips coupled with silicon photomultipliers (SiPMs) for high sensitive real-time ATP detection. The 3D microfluidic chip reduces reactant consumption and facilitates solution delivery close to the SiPM to increase the detection efficiency. Our system detects ATP with a limit of detection (LoD) of 8nM and an analytical dynamic range between 15nM and 1µM, showing a stability error of 3%, and a reproducibility error below of 20%. We demonstrate the dynamic monitoring of ATP in a continuous-flow system exhibiting a fast response time, ~4s, and a full recovery to the baseline level within 17s. Moreover, the SiPM-based bioluminescence sensing system shows a similar analytical dynamic range for ATP detection to that of a full-size PerkinElmer laboratory luminescence reader.

Thermo-rheological responsive microcapsules for time-dependent controlled release of human mesenchymal stromal cells.

Human mesenchymal stromal cells (hMSCs) are adult-source cells that have been extensively evaluated for cell-based therapies. hMSCs delivered by intravascular injection have been reported to accumulate at the sites of injury to promote tissue repair and can also be employed as vectors for the delivery of therapeutic genes. However, the full potential of hMSCs remains limited as the cells are lost after injection due to anoikis and the adverse pathologic environment. Encapsulation of cells has been proposed as a means of increasing cell viability. However, controlling the release of therapeutic cells over time to target tissue still remains a challenge today. Here, we report the design and development of thermo-rheological responsive hydrogels that allow for precise, time dependent controlled-release of hMSCs. The encapsulated hMSCs retained good viability from 76% to 87% dependent upon the hydrogel compositions. We demonstrated the design of different blended hydrogel composites with modulated strength (S parameter) and looseness of hydrogel networks (N parameter) to control the release of hMSCs from thermo-responsive hydrogel capsules. We further showed the feasibility for controlled-release of encapsulated hMSCs within 3D matrix scaffolds. We reported for the first time by a systematic analysis that there is a direct correlation between the thermo-rheological properties associated with the degradation of the hydrogel composite and the cell release kinetics. This work therefore provides new insights into the further development of smart carrier systems for stem cell therapy.

Use of ICSI in IVF cycles in women with tubal ligation does not improve pregnancy or live birth rates.

STUDY QUESTION: Does ICSI improve outcomes in ART cycles without male factor, specifically in couples with a history of tubal ligation as their infertility diagnosis? SUMMARY ANSWER: The use of ICSI showed no significant improvement in fertilization rate and resulted in lower pregnancy and live birth (LB) rates for women with the diagnosis of tubal ligation and no male factor. WHAT IS KNOWN ALREADY: Prior studies have suggested that ICSI use does not improve fertilization, pregnancy or LB rates in couples with non-male factor infertility. However, it is unknown whether couples with tubal ligation only diagnosis and therefore iatrogenic infertility could benefit from the use of ICSI during their ART cycles. STUDY DESIGN, SIZE, DURATION: Longitudinal cohort of nationally reported cycles in the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) of ART cycles performed in the USA between 2004 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: There was a total of 8102 first autologous fresh ART cycles from women with the diagnosis of tubal ligation only and no reported male factor in the SART database. Of these, 957 were canceled cycles and were excluded from the final analysis. The remaining cycles were categorized by the use of conventional IVF (IVF, n = 3956 cycles) or ICSI (n = 3189 cycles). The odds of fertilization, clinical intrauterine gestation (CIG) and LB were calculated by logistic regression modeling, and the adjusted odds ratios (AORs) with 95% confidence intervals were calculated by adjusting for the confounders of year of treatment, maternal age, race and ethnicity, gravidity, number of oocytes retrieved, day of embryo transfer and number of embryos transferred. MAIN RESULTS AND THE ROLE OF CHANCE: The main outcome measures of the study were odds of fertilization (2PN/total oocytes), clinical intrauterine gestation (CIG/cycle) and live birth (LB/cycle). The fertilization rate was higher in the ICSI versus IVF group (57.5% vs 49.1%); however, after adjustment this trend was no longer significant (AOR 1.14, 0.97-1.35). Interestingly, both odds of CIG (AOR 0.78, 0.70-0.86), and odds of LB were lower (AOR 0.77, 0.69-0.85) in the ICSI group. Plurality at birth, mean length of gestation and birth weight did not differ between the two groups. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study, therefore only the available parameters could be included, with parameters of interest such as smoking status not available for inclusion. Smoking status may have led practitioners to use ICSI to improve pregnancy and LB outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Studies have shown that in the USA there is an increasing usage of ICSI for non-male factor infertility despite a lack of evidence-based benefit. Our study corroborates this increasing use over the last 8 years, specifically in the tubal ligation only patient population. Even after adjusting for multiple confounders, the patients who underwent ICSI had no statistically significant improvement in fertilization rate and actually had a lower likelihood of achieving a clinical pregnancy and LB. Therefore, our data suggest that the use of ICSI in tubal ligation patients has no overall benefit. This study contributes to the body of evidence that the use of ICSI for non-male factor diagnosis does not improve ART outcomes over conventional IVF. STUDY FUNDING/COMPETING INTERESTS: None.