Physiologic Variants of Cardiac Conduction (Aberration, Gap, Supernormal Conduction).

Wide QRS complexes during supraventricular rhythms can be caused by fixed bundle branch block, functional (intermittent) bundle branch block, preexcitation, or toxic/metabolic causes. Functional bundle branch block can be caused by long-short aberrancy (usually physiologic), or acceleration/deceleration dependent aberrancy (usually pathologic). Electrocardiogram criteria have been proposed to differentiate aberration from ventricular tachycardia; they are not always accurate. The gap phenomenon "paradox" is that with increasingly premature extrastimuli, progressive proximal conduction delay allows time for distal recovery of excitability. Supernormal conduction may explain unusual conduction phenomena in patients with abnormal His-Purkinje function or poorly conducting accessory pathways.

Thoracoscopic Left Atrial Appendage Exclusion for Atrial Fibrillation Patients Intolerant to Anticoagulation.

OBJECTIVE: Outcomes associated with isolated epicardial left atrial appendage (LAA) exclusion in atrial fibrillation (AF) patients with a contraindication or intolerance to anticoagulation are not clearly defined, especially in patients with prior stroke. This study evaluated the perioperative safety, medication use, and stroke outcomes for isolated thoracoscopic LAA exclusion for stroke prevention. METHODS: A single-center retrospective study was performed of adults undergoing isolated thoracoscopic LAA exclusion with an epicardial exclusion device without a concomitant surgical procedure. Descriptive statistics were performed. RESULTS: Twenty-five patients met the inclusion criteria. The cohort was 68% male (n = 17) with a mean age of 76.4 ± 6.5 years, a mean preoperative CHA2DS2-VASc score of 4.2 ± 1.4, and a mean preoperative HAS-BLED score of 2.68 ± 1.03. Seventeen patients (68%) had nonparoxysmal AF. There were 11 patients with intolerance of anticoagulation due to intracranial hemorrhage (44%), 6 due to gastrointestinal bleeding (24%), and 4 due to genitourinary bleeding (16%). All procedures were performed thoracoscopically with 100% technical success-the mean LAA stump length was 5.5 ± 2.3 mm on intraoperative transesophageal echocardiography. The median hospital length of stay was 2 (interquartile range [IQR] 1, 6.5) days. The median follow-up time was 430 (IQR 125, 972) days. During follow-up, 1 patient with cerebral angiopathy had temporary neurologic deficits at an outside institution, with brain imaging showing no evidence of ischemic injury. There were no other thromboembolic events over the 38.8 postoperative patient-years examined. All patients were off anticoagulation at last follow-up. CONCLUSIONS: This study shows the perioperative safety, technical success, freedom from anticoagulation, and stroke outcomes of isolated thoracoscopic LAA exclusion in patients with AF at high risk for thromboembolic disease.

Role of Ultrasonography in Upper Airway Assessment for Decannulating Tracheostomy in Acquired Brain Injury-A Pilot Study.

OBJECTIVE: To compare the findings of ultrasonography of the upper airway with flexible fiberoptic laryngoscopy and determine the efficacy of transcutaneous laryngeal ultrasonography for decannulation. DESIGN: Prospective cross-sectional study. SETTING: Tertiary care referral center in South India. PARTICIPANTS: Twenty-four patients with acquired brain injury (N=24). MAIN OUTCOME MEASURES: Participants underwent an airway assessment by ultrasonography followed by assessment of airway by flexible laryngoscopy done within the next 72 hours. RESULTS: Vocal cord assessment by ultrasonography revealed a sensitivity of 81.2% and specificity of 87.5%. A statistically significant association between vocal cord mobility as assessed by ultrasonography and decannulation was observed (sensitivity of 81.25%, specificity of 87.5%, P=.002). Although aspiration was not assessed by ultrasonography, a statistically significant association was observed between vocal cord mobility on ultrasonography and aspiration as assessed by laryngoscopy (sensitivity of 81.25%, specificity of 87.5%, P=.011). CONCLUSION: Laryngeal ultrasonography is an emerging diagnostic modality with a potential role for assessing vocal cord mobility and airway prior to decannulation in centers that lack the expertise and the infrastructure to perform a flexible laryngoscopy.

Covid-19, not your normal flu: A case report on Covid-19 psychosis and mania in a Malaysian hospital.

Evidence suggests that acute severe coronavirus disease 2019 (COVID-19) may be associated with neuropsychiatric symptoms. This is a case report of a patient who had recently been infected with COVID-19 and had no history of psychiatric disorders presenting a few days after inpatient discharge from COVID-19 treatment with acute onset of psychosis and manic symptoms. This case illustrates the psychiatric presentation, possible causes, and management of post-COVID-19 psychosis.

Physiologic Variants of Cardiac Conduction (Aberration, Gap, Supernormal Conduction).

Wide QRS complexes during supraventricular rhythms can be caused by fixed bundle branch block, functional (intermittent) bundle branch block, preexcitation, or toxic/metabolic causes. Functional bundle branch block can be caused by long-short aberrancy (usually physiologic), or acceleration/deceleration dependent aberrancy (usually pathologic). Electrocardiogram criteria have been proposed to differentiate aberration from ventricular tachycardia; they are not always accurate. The gap phenomenon "paradox" is that with increasingly premature extrastimuli, progressive proximal conduction delay allows time for distal recovery of excitability. Supernormal conduction may explain unusual conduction phenomena in patients with abnormal His-Purkinje function or poorly conducting accessory pathways.

Origins of the threshold for surgical intervention in intra-articular distal radius fractures.

AIMS: The aim of this study was to identify the origin and development of the threshold for surgical intervention, highlight the consequences of residual displacement, and justify the importance of accurate measurement. METHODS: A systematic review of three databases was performed to establish the origin and adaptations of the threshold, with papers screened and relevant citations reviewed. This search identified papers investigating functional outcome, including presence of arthritis, following injury. Orthopaedic textbooks were reviewed to ensure no earlier mention of the threshold was present. RESULTS: Knirk and Jupiter (1986) were the first to quantify a threshold, with all their patients developing arthritis with > 2 mm displacement. Some papers have discussed using 1 mm, although 2 mm is most widely reported. Current guidance from the British Society for Surgery of the Hand and a Delphi panel support 2 mm as an appropriate value. Although this paper is still widely cited, the authors published a re-examination of the data showing methodological flaws which is not as widely reported. They claim their conclusions are still relevant today; however, radiological arthritis does not correlate with the clinical presentation. Function following injury has been shown to be equivalent to an uninjured population, with arthritis progressing slowly or not at all. Joint space narrowing has also been shown to often be benign. CONCLUSION: Knirk and Jupiter originated the threshold value of 2 mm. The lack of correlation between the radiological and clinical presentations warrants further modern investigation. Measurement often varies between observers, calling a threshold concept into question and showing the need for further development in this area. The principle of treatment remains restoration of normal anatomical position. Cite this article: Bone Joint J 2021;103-B(9):1457-1461.

Chimeric antigen receptor T-cells in New Zealand: challenges and opportunities.

Chimeric antigen receptor (CAR) T-cells are a personalised cell and gene therapy for cancer that are becoming an international standard of care for some refractory B-cell leukaemias, non-Hodgkin lymphomas and myeloma. A single CAR T-cell administration can result in durable complete response for some recipients. Domestic CAR T-cell manufacturing capability was established for Aotearoa New Zealand's first CAR T-cell trial (ENABLE, ClinicalTrials.gov NCT04049513). This article outlines CAR T-cell manufacturing and logistical considerations, with a focus on New Zealand's environment for this personalised cell and gene therapy. We discuss Maori engagement in CAR T-cell trial and clinical service design, and propose enhancing Maori guardianship (kaitiakitanga) over cells and genetic material through on-shore manufacture. Strategies to safely deliver CAR T-cells within New Zealand's healthcare system are outlined. Finally, we discuss challenges to, and opportunities for, widening CAR T-cell availability and assuring equity of access. Based on our experience, we consider Aotearoa New Zealand to be in an excellent position to develop and implement investigational and commercial CAR T-cell therapies in the future.

The Association of Human Papillomavirus in Benign and Malignant Laryngeal Lesions-a Pilot Study.

Various etiological factors have been described in laryngeal carcinogenesis. Tobacco and alcohol play a major role in the development of laryngeal cancers. However, recently there has been an overshadowing of association of human papillomavirus infection in laryngeal cancers. The aim of this study is to assess the prevalence of human papillomavirus (HPV) in malignant laryngeal lesions. This is a case control study. We conducted this study using tumor tissue specimens from 30 laryngeal squamous cell carcinoma patients and benign laryngeal tissue specimens from 30 cancer-free controls. The specimens from the lesion were sent to histopathological analysis as well as DNA extraction (DNeasy® Tissue kit) and polymerase chain reaction for detection of HPV. Positive samples underwent sequencing to detect the HPV serotype. Statistical analysis was performed using SPSS software. All 30 benign laryngeal lesion specimens were negative for the HPV DNA, while 4 of the 30 (7.5%) squamous cell carcinoma lesions were positive. One was HPV 16 and another one HPV 11. Two positive cases were not able to be sequenced probably due to low viral load. Our study suggests that the proportion of laryngeal squamous cell carcinomas attributable to infection by HPV seems to be low. Further prospective studies should be conducted with a larger group of patients to confirm the role of HPV in laryngeal cancers especially in treatment response and survival.

Impact of Body Mass Index (BMI) on perioperative outcomes following minimally invasive retromuscular abdominal wall reconstruction: a comparative analysis.

BACKGROUND: Morbidity and recurrence rates are higher in obese patients undergoing open abdominal wall reconstruction (AWR). Historically, body mass index (BMI) ≥ 40 has served as a relative contraindication to open AWR. The purpose of this study is to evaluate the impact of minimally invasive surgery (MIS) on outcomes after AWR for higher versus lower BMI patients. METHODS: A retrospective review of a prospectively maintained database was conducted of all patients who underwent MIS AWR between September 2015 and April 2019 at our institution. Patients were subdivided into two groups based on their BMI: BMI ≤ 35 kg/m2 and BMI > 35 kg/m2. Patient demographics and perioperative data were evaluated using univariate and multivariate analysis. RESULTS: 461 patients were identified and divided into two groups: BMI ≤ 35 (n = 310) and BMI > 35 (n = 151). The two groups were similar in age (BMI ≤ 35: 56.3 ± 14.1 years vs. BMI > 35: 54.4 ± 11.9, p = .154). BMI > 35 group had more patients with ASA score of 3 (81% vs. 32%, p < .001) and comorbid conditions such as hypertension (70% vs. 45%, p < .001), diabetes mellitus (32% vs. 15%, p < .001), and history of recurrent abdominal wall hernia (34% vs. 23%, p = .008). BMI > 35 group underwent a robotic approach at higher rates (74% vs. 45%, p < .001). Patients who underwent a Rives-Stoppa repair from the higher BMI cohort also had a larger defect size (5.6 ± 2.4 cm vs. 6.7 ± 2.4 cm, p = .004). However, there were no differences in defect size in patients who underwent a transversus abdominus release (BMI ≤ 35: 9.7 ± 4.9 cm vs. BMI > 35: 11.1 ± 4.6 cm, p = .069). Both groups benefited similarly from a short length of stay, similar hospital charges, and lower postoperative complications. CONCLUSION: Initial findings of our data support the benefits of elective MIS approach to AWR for patients with higher BMI. These patients derive similar benefits, such as faster recovery with low recurrence rates, when compared to lower BMI patients, while avoiding preoperative hernia incarceration, postoperative wound complications, and hernia recurrences. Future follow-up is required to establish long-term perioperative and quality of life outcomes in this patient cohort.

Hybrid versus open retromuscular abdominal wall repair: early outcomes.

BACKGROUND: The hybrid approach to abdominal wall reconstruction (AWR) for abdominal wall hernias combines minimally invasive posterior component separation and retromuscular dissection with open fascial closure and mesh implantation. This combination may enhance patient outcomes and recovery compared to the open approach alone. The purpose of this study is to evaluate the operative outcomes of hybrid vs. open abdominal wall reconstruction. METHODS: A retrospective review was conducted to compare patients who underwent open versus hybrid AWR between September 2015 and August of 2018 at Anne Arundel Medical Center. Patient demographics and perioperative data were collected and analyzed using univariate analysis. RESULTS: Sixty-five patients were included in the final analysis: 10 in the hybrid and 55 in the open groups. Mean age was higher in the hybrid vs. open group (65.1 vs. 56.2 years, p < 0.05). The hybrid and open groups were statistically similar (p > 0.05) in gender distribution, mean BMI, and ASA score. Intraoperative comparison found hybrid patients parallel to open patients (p > 0.05) in mean operative time (294.5 vs. 267.5 min), defect size (14.4 vs. 13.6 cm), mesh area, and drain placement. The mean total hospital cost was lower in the hybrid group compared to the open group ($16,426 vs. $19,054, p = 0.43). The hybrid group had a shorter length of stay (5.3 vs. 3.6 days, p = 0.03) after surgery and was followed for a similar length of time (12.3 vs. 12.6 months, p = 0.91). The hybrid group showed a lower trend of seroma, hematoma, wound infection, ileus, and readmission rates after surgery. CONCLUSION: A review of patient outcomes after hybrid AWR highlights a trend towards shorter length of stay, lower hospital cost, and fewer complications without significant addition to operative time. Long-term studies on a larger number of patients are definitively needed to characterize the comprehensive benefits of this approach.

Patients with ineffective esophageal motility benefit from laparoscopic antireflux surgery.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common chronic disorder of the gastrointestinal tract, affecting more than 50% of Americans. The development of GERD may be associated with ineffective esophageal motility (IEM). The impact of esophageal motility on outcomes post laparoscopic antireflux surgery (LARS), including quality of life (QOL), remains to be defined. The purpose of this study is to analyze and compare QOL outcomes following LARS among patients with and without ineffective esophageal motility (IEM). METHODS: This is a single-institution, retrospective review of a prospectively maintained database of patients who underwent LARS, from January 2012 to July 2019, for treatment of GERD at our institution. Patients undergoing revisional surgery were excluded. Patients with normal peristalsis (non-IEM) were distinguished from those with IEM, defined using the Chicago classification, on manometric studies. Four validated QOL surveys were used to assess outcomes: Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease Health-Related QOL (GERD-HRQL), Laryngopharyngeal Reflux Health-Related QOL (LPR-HRQL), and Swallowing Disorders (SWAL) survey. RESULTS: 203 patients with complete manometric data were identified (75.4% female) and divided into two groups, IEM (n = 44) and non-IEM (n = 159). IEM and Non-IEM groups were parallel in age (58.1 ± 15.3 vs. 62.2 ± 12 years, p = 0.062), body mass index (27.4 ± 4.1 vs. 28.2 ± 4.9 kg/m2, p = 0.288), distribution of comorbid disease, sex, and ASA scores. The groups differed in manometry findings and Johnson-DeMeester score (IEM: 38.6 vs. Non-IEM: 24.0, p = 0.023). Patients in both groups underwent similar rates of Nissen fundoplication (IEM: 84.1% vs. Non-IEM: 93.7%, p = 0.061) with greater improvements in dysphagia (IEM: 27.4% vs. 44.2%) in Non-IEM group but comparable benefit in reflux reduction (IEM: 80.6% vs. 72.4%) in both groups at follow-up. There were no differences in postoperative outcomes. Satisfaction rates with LARS were similar between groups (IEM: 80% vs. non-IEM: 77.9%, p > 0.05). CONCLUSION: Patients with ineffective esophageal motility derive significant benefits in perioperative and QOL outcomes after LARS. Nevertheless, as anticipated, their baseline dysmotility may reduce the degree of improvement in dysphagia rates post-surgery compared to patients with normal motility. Furthermore, the presence of preoperative IEM should not be a contraindication for complete fundoplication. Key to optimal outcomes after LARS is careful patient selection based on objective perioperative data, including manometry evaluation, with the purpose of tailoring surgery to provide effective reflux control and improved esophageal clearance.

Bilateral total conservative parotidectomy: a tale behind an aesthetic surgery.

Any facial swelling is associated with stress for the patient due to cosmesis. Especially when one has bilateral symmetrical enlarged parotids, having exhausted all available conservative management, surgery becomes the last resort; which in such cases pose specific challenges. A 29-year-old man presented with problems of bilateral symmetrical enlarged parotid lesion for 5 years, which did not have an adequate response to medical line of management. He underwent proposed surgery and was diagnosed to have chronic sclerosing parotitis (CSS). The challenges faced during surgery of this non-neoplastic inflammatory lesion, with significant fibrosis, is being described. He recovered completely without any complications related to surgery. CSS rarely affects bilateral parotid glands. Surgery, results of which are outstanding, must be considered in cases where these lesions do not respond to medical line of management. Bilateral total conservative parotidectomy with sternocleidomastoid flap reconstruction provides excellent aesthesis and improves quality of life.

Management of the Thyroid Gland in Papillary Carcinoma of the Thyroglossal Cyst: A Case Report.

Carcinoma arising in a thyroglossal cyst is rare. We present a case of anterior neck swelling diagnosed to be thyroglossal cyst clinically which turns out to be a papillary carcinoma arising in thyroglossal cyst. She underwent sistrunk procedure with total thyroidectomy and diseasefree on follow up evaluation. Even though preoperative ultrasonography had shown thyroid nodule, the final histology did not show malignancy. There is a paucity of clear-cut guidelines in the management of the thyroid gland in a thyroglossal cyst carcinoma. In thyroglossal cyst carcinoma cases, we recommend thyroidectomy only when there is a thyroid nodule with high-risk features.

Cardiovascular Considerations for the Internist and Hospitalist in the COVID-19 Era.

It is clear that existing cardiovascular disease is a major risk factor for COVID-19 and related adverse outcomes. In addition to acute respiratory syndrome, a large cohort also develop myocardial or vascular dysfunction, in part from inflammation and renin angiotensin system activation with increased sympathetic outflow, cardiac arrhythmias, ischemia, heart failure, and thromboembolic complications that portend poor outcomes related to COVID-19. We summarize recent information for hospitalists and internists on the front line of this pandemic regarding its cardiovascular impacts and management and the need for cardiovascular consultation.

Chimeric antigen receptor T-cell therapies: Optimising the dose.

Lymphocytes such as T-cells can be genetically transduced to express a synthetic chimeric antigen receptor (CAR) that re-directs their cytotoxic activity against a tumour-expressed antigen of choice. Autologous (patient-derived) CAR T-cells have been licensed to treat certain relapsed and refractory B-cell malignancies, and numerous CAR T-cell products are in clinical development. As living gene-modified cells, CAR T-cells exhibit unique pharmacokinetics, typically proliferating within the recipient during the first 14 days after administration before contracting in number, and sometimes exhibiting long-term persistence. The relationship between CAR T-cell dose and exposure is highly variable, and may be influenced by CAR design, patient immune function at the time of T-cell harvest, phenotype of the CAR T-cell product, disease burden, lymphodepleting chemotherapy and subsequent immunomodulatory therapies. Recommended CAR T-cell doses are typically established for a specific product and indication, although for some products, stratification of dose based on disease burden may mitigate toxicity while maintaining efficacy. Re-evaluation of CAR T-cell dosing may be necessary following changes to the lymphodepleting regimen, for different disease indications, and following significant manufacturing changes, if product comparability cannot be demonstrated. Dose escalation trials have typically employed 3 + 3 designs, although this approach has limitations, and alternative phase I trial designs may facilitate the identification of CAR T-cell doses that strike an optimal balance of safety, efficacy and manufacturing feasibility.

Third-generation anti-CD19 chimeric antigen receptor T-cells incorporating a TLR2 domain for relapsed or refractory B-cell lymphoma: a phase I clinical trial protocol (ENABLE).

INTRODUCTION: Autologous T-cells transduced to express a chimeric antigen receptor (CAR) directed against CD19 elicit high response rates in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). However, r/r B-NHL remissions are durable in fewer than half of recipients of second-generation CAR T-cells. Third-generation (3G) CARs employ two costimulatory domains, resulting in improved CAR T-cell efficacy in vitro and in animal models in vivo. This investigator-initiated, phase I dose escalation trial, termed ENABLE, will investigate the safety and preliminary efficacy of WZTL-002, comprising autologous T-cells expressing a 3G anti-CD19 CAR incorporating the intracellular signalling domains of CD28 and Toll-like receptor 2 (TLR2) for the treatment of r/r B-NHL. METHODS AND ANALYSIS: Eligible participants will be adults with r/r B-NHL including diffuse large B-cell lymphoma and its variants, follicular lymphoma, transformed follicular lymphoma and mantle cell lymphoma. Participants must have satisfactory organ function, and lack other curative options. Autologous T-cells will be obtained by leukapheresis. Following WZTL-002 manufacture and product release, participants will receive lymphodepleting chemotherapy comprising intravenous fludarabine and cyclophosphamide. A single dose of WZTL-002 will be administered intravenously 2 days later. Targeted assessments for cytokine release syndrome and immune cell effector-associated neurotoxicity syndrome, graded by the American Society Transplantation and Cellular Therapy criteria, will be made. A modified 3+3 dose escalation scheme is planned starting at 5×104 CAR T-cells/kg with a maximum dose of 1×106 CAR T-cells/kg. The primary outcome of this trial is safety of WZTL-002. Secondary outcomes include feasibility of WZTL-002 manufacture and preliminary measures of efficacy. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the New Zealand Health and Disability Ethics Committee (reference 19/STH/69) on 23 June 2019 for Protocol V.1.2. Trial results will be reported in a peer-reviewed journal, and results presented at scientific conferences or meetings. TRIAL REGISTRATION NUMBER: NCT04049513.