Professor PEP Petros DSc DS (UWA) PhD (Uppsala) MB BS MD (Syd) FRCOG (Lond)31/93 Elizabeth Bay Rd, Elizabeth Bay NSW 2011 AUSTRALIAReconstructive Pelvic Floor Surgeon and Certified Urogynaecologist (retired)Formerly University of NSW Professorial Dept of Surgery, St Vincent’s Hospital Sydney (retired)Adjunct Professor, University of Western Australia School of Mechanical and Chemical Engineering, Perth WA (current)Tel 61 2 9361 3853 Cellphone (AUST) 61 411 181 731Email email@example.com website www.integraltheory.org
The called burden of cardiac heart failure (CHF) on healthcare systems and economies remains large and a major factor contributing to this burden is the high hospital admission rate for acute decompensated heart failure. These repeated heart failure hospitalizations (HFH) not only exert a high burden on healthcare systems, but also impact patient quality of life and have been associated with impaired prognosis and reduced life expectancy. The need for remote monitoring has become extremely important, mainly based on devices capable of measuring intracardiac filling pressures. If we assume that hemodynamic congestion precedes clinical congestion, the hemodynamic monitoring could be able to detect early signs of congestion and enables clinicians to intervene in a pre-symptomatic phase avoiding hospital admission. Dr. Veenis JF and colleagues present the results of implanting the CardioMEMS device in 10 patients who underwent heartmate 3 implantation. The authors describe the study design based on an earlier publication by the same author. The authors argue that the use of this device will allow the monitoring of patients pre, during hospitalization and after implantation, with a possible reduction in the number of readmissions for allowing the diagnosis and treatment of complications related to ventricular failure and volume overload.
Title: Notch4, uncovering an immunomodulator in allergic asthmaAuthors: Beatriz Moyaa,b, Manali Mukherjeec and Parameswaran Nairca. Department of Allergy, Hospital Universitario 12 de Octubre, Madrid, Spainb. Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spainc. Division of Respirology, Department of Medicine, McMaster University, Hamilton & Firestone Institute for Respiratory Health, St Joseph’s Healthcare, Hamilton, ON, CanadaCorrespondence to : Beatriz Moya. Allergy Department. Hospital Universitario 12 de Octubre, Madrid, SpainEmail:firstname.lastname@example.orgAcknowledgements : Dr. Mukherjee is supported by investigator award from Canadian Institutes of Health Research and Canadian Allergy, Asthma, and Immunology Foundation. She has received honorarium from AZ, GSK and her university has received grants from Methapharm Speciality Pharmaceuticals. Dr. Nair is supported by the Frederick E. Hargreave Teva Innovation Chair in Airway Diseases. He has received honoraria from AZ, Sanofi, Teva, Merck, Novartis and Equillium and his university has received research grants from AZ, Teva, Sanofi, Novartis, BI and Methapharm. The authors recognize Dr. Anna Globinska for graphical abstract design and Dr. Rodrigo Jiménez-Saiz for critical review of the manuscript.Keywords: Allergic asthma; Airway inflammation; Th2 cell; Th17 cell; Treg cell; Notch4 receptorAbbreviations: Th, T helper; UFPs, pollutant ultrafine particles; AMs, alveolar macrophages; Treg cells, regulatory T cells; ILC2s, type 2 innate lymphoid cells; GDF15, cytokine growth and differentiation factor 15; IL, interleukin; IL-6R, interleukin-6 receptor; IL-4R, interleukin-4 receptorWord count: 918/1000
Background: The high incidence of postoperative pulmonary venous obstruction (PVO) is a major mortality-associated concern in patients with right atrial isomerism and extracardiac total anomalous pulmonary venous connection (TAPVC). We evaluated new anatomical risk factors for reducing the space behind the heart after TAPVC repair. Methods: 18 patients who underwent TAPVC repair between 2014 and 2020 were enrolled. Sutureless technique was used in 12 patients and conventional repair in six patients. The angle between the line perpendicular to the vertebral body and that from the vertebral body to the apex was defined as the “vertebral-apex angle (V-A angle).” The ratio of post- and preoperative angles, indicating the apex’s lateral rotation, was compared between patients with and without PVO. Results: The median (interquartile range) age and body weight at repair were 102 (79-176) days and 3.8 (2.6-4.8) kg, respectively. The 1-year survival rate was 83% (median follow-up, 29 [11-36] months). PVO occurred in seven patients (39%), who showed an obstruction of one or two branches in the apex side. The postoperative V-A angle (46° [45°-50°] vs. 36° [29°-38°], P = 0.001) and the ratio of post- and preoperative V-A angles (1.27 [1.24-1.42] vs. 1.03 [0.98-1.07], P = 0.001) were significantly higher in the PVO group than in the non-PVO group. The cut-off values of the postoperative V-A angle and ratio were 41° and 1.17, respectively. Conclusions: A postoperative rotation of the heart apex into the ipsilateral thorax was a risk factor for branch PVO after TAPVC repair.
Background: This study aims at better defining the profile of patients with a complicated versus non-complicated postoperative course following isolated tricuspid valve (TV) surgery to identify predictors of a favourable/unfavourable hospital outcome. Methods: All patients treated with isolated tricuspid surgery from March 1997-January 2020 at our institution were retrospectively reviewed. Considering the complexity of most of these patients, a regular postoperative course was arbitrarily defined as a length-of-stay in intensive care unit <4 days and/or postoperative length-of-stay <10days. Patients were therefore divided accordingly in two groups. Results: 172 patients were considered, among whom 97 (56.3%) had a regular (REG) and 75 (43.6%) a non-regular (NEG) postoperative course. The latter had worse baseline clinical and echocardiographic characteristics, with higher rate of renal insufficiency, previous heart failure hospitalizations, cardiac operations, and right ventricular dysfunction. NEG patients more frequently needed tricuspid replacement and experienced a greater number of complications (p<0.001) and higher in-hospital mortality (13% vs 0%, p<0.001). The majority of these complications were related to more advanced stage of the tricuspid disease. Among most important predictors of a negative outcome univariate analysis identified chronic kidney disease, ascites, previous right heart failure hospitalizations, right ventricular dysfunction, previous cardiac surgeries, TV replacement and higher MELD scores. At multivariate analysis, liver enzymes and diuretics’ dose were predictors of complicated postoperative course. Conclusions: In isolated TV surgery a complicated postoperative course is observed in patients with more advanced right heart failure and organ damage. Earlier surgical referral is associated to excellent outcomes and should be recommended.
BJOG-20-2353.R2 What should we believe when systematic reviews disagree?For many years, uterine balloon tamponade (UBT) has been used to treat severe postpartum haemorrhage (PPH), despite a lack of randomised trials to demonstrate its effectiveness. With commercial devices being expensive, clinicians in low resource settings have made their own using 2 low-cost, widely available items (Foley catheters and condoms). Public health experts have been so confident of their benefit that large programmes have been set up to disseminate the necessary skills worldwide.Recently, however, the global maternal health community has been thrown into disarray when not one, but two randomised controlled efficacy trials suggested that outcomes with condom catheter UBTs were actuallyworse than normal care in low resource settings. The Cochrane meta-analysis concluded that “in [low resource] settings, balloon tamponade [should be] only introduced alongside multi‐system improvements in PPH care” (Kellie et al. Cochrane Database of Systematic Reviews 2020(7): CD013663).Systematic reviews may be the pinnacle of evidence-based medicine, but even they can differ in how to interpret evidence. And so, proponents of the condom catheter conducted their own systematic review with far wider inclusion criteria – they not only included the randomised trials but examined success rates from 15 non-randomised trials and 69 case series (Suarez et al. Am J Obstet Gynecol 2020;222(4):293.e1–e52). Furthermore, the primary outcome was the success rate of the technique (overall 86%) rather than the risk of morbidity and mortality compared to controls, as used in the Cochrane review. This is problematic, as reported ‘success rates’ without controls can be very difficult to interpret: in initial case series misoprostol showed similar success rates against life-threatening haemorrhage before RCTs eventually showed it to be less effective than oxytocin.A third version of the same review is published today by a WHO team (Pingray et al. BJOG 2021;XXX,XXX). This time they include only 4 high quality studies in which UBT was compared to standard care. With a composite maternal morbidity / mortality outcome, they found no evidence of benefit and concluded that “the effect … is unclear, as is the role of the type of device and the setting”. WHO studies are now underway to address this uncertainty.But why is this all so important? The difficulty comes because the World Health Organisation has been updating its guidance on PPH management, and had to declare a position on UBT. The recently-published guideline, drawn up by independent experts, accepts the validity of the RCTs but recognises that there is wide acceptability of the technique and that the evidence of harm is only for condom catheters and onlyin resource-poor settings. They put a high emphasis on minimising harm and conclude that UBTs should only be used in settings where there is already a good standard of care, including recourse to blood transfusion and surgery if needed (WHO. Geneva: World Health Organization; 2021).Until further studies are published, the debate will continue. But this episode shows how the choice of inclusion criteria and outcomes in systematic reviews are critical, both for their conclusions, and for global policy.
Objectives Possibility of reinfection with SARS-CoV-2 changes our view on herd immunity and vaccination, and can impact worldwide quarantine policies. We performed RT-PCR follow-up studies on recovered patients to assess possible development of reinfections and re-positivity. Method During a 6-month period, 202 PCR-confirmed recovering COVID-19 patients entered this study. Follow-up RT-PCR tests and symptoms assessment were performed one month after the initial Positive results. patients who tested negative were tested again one and three months later. The Serum IgG and IgM levels were measured in the last follow-up session. Results In the first two follow-up sessions, 82 patients continued their participation, of which four patients tasted positive. In the second follow-up 44 patients participated, three of whom tested positive. None of the patients who tested positive in the first and second follow-up session were symptomatic. In the last session, 32 patients were tested and four patients were positive, three of them were mildly symptomatic and all of them were positive for IgG. Conclusion A positive RT-PCR in a recovering patient may represent reinfection. While we did not have the resources to prove reinfection by genetic sequencing of the infective viruses, we believe presence of mild symptoms in the three patients who tested positive over 100 days after becoming asymptomatic, can be diagnosed as reinfection. The IgG may have abated the symptoms of the reinfection, without providing complete protection.
Since the start of the SARS-CoV-2 pandemic, it has been difficult to differentiate between SARS-CoV-2 re-infection and prolonged RNA shedding. In this report, we identified patients with positive rtPCR results for SARS-CoV-2 ≥70 days apart. Clinical and laboratory data were collected and criteria were applied to discern whether the presentation was consistent with SARS-CoV-2 re-infection or prolonged viral RNA shedding. Eleven individuals met the initial testing criteria, of which, seven met at least one criteria for re-infection and four were consistent with prolonged RNA shedding. These data demonstrate the need for criteria to differentiate SARS-CoV-2 re-infection from prolonged RNA shedding.
How variations in carbon supply affect wood formation remains poorly understood in particular in mature forest trees. To elucidate how carbon supply affects carbon allocation and wood formation, we attempted to manipulate carbon supply to the cambial region by phloem girdling and compression during the mid- and late-growing season and measured effects on structural development, CO2 efflux, and nonstructural carbon reserves in stems of mature white pines. Wood formation and stem CO2 efflux varied with location relative to treatment (i.e., above or below the restriction). We observed up to twice as many tracheids formed above versus below the treatment after the phloem transport manipulation, whereas cell-wall area decreased only slightly below the treatments, and cell size did not change relative to the control. Nonstructural carbon reserves in the xylem, needles, and roots were largely unaffected by the treatments. Our results suggest that low and high carbon supply affects wood formation, primarily through a strong effect on cell proliferation, and respiration, but local nonstructural carbon concentrations appear to be maintained homeostatically. This contrasts with reports of a decoupling of source activity and wood formation at the whole-tree or ecosystem level, highlighting the need to better understand organ-specific responses, within-tree feedbacks, as well as phenological and ontological effects on sink-source dynamics.
African Swine Fever Virus (ASFV) causes a deadly disease of pigs which spread through southeast Asia in 2019. We investigated one of the first outbreaks of ASFV in Lao Peoples Democratic Republic amongst smallholder villages of Thapangtong District, Savannakhet Province. In this study, two ASFV affected villages were compared to two unaffected villages. Evidence of ASFV-like clinical signs appeared in pig herds as early as May 2019, with median epidemic days on 1 and 18 June in the two villages, respectively. Using participatory epidemiology mapping techniques, we found statistically significant spatial clustering in both outbreaks (P < 0.001). Villagers reported known risk factors for ASFV transmission − such as free-ranging management systems and wild boar access − in all four villages. The villagers reported increased pig trader activity from Vietnam before the outbreaks; however, the survey did not determine a single outbreak source. The outbreak caused substantial household financial losses with an average of 9 pigs lost to the disease, and Monte Carlo analysis estimated this to be USD 215 per household. ASFV poses a significant threat to food and financial security in smallholder communities such as Thapangtong, where 40.6% of the district’s population are affected by poverty. This study shows ASFV management in the region will require increased local government resources, knowledge of informal trader activity and wild boar monitoring alongside education and support to address intra-village risk factors such as free-ranging, incorrect waste disposal and swill feeding.
Isolated cecal necrosis is a rare variant of ischemic colitis which typically simulates the presentation of acute appendicitis. The elderly population is the most affected. We report 2 cases of isolated caecal necrosis, which were preoperatively diagnosed, in 2 female patients with a history of hypertension and renal failure.
The safety of transesophageal echocardiography (TEE) probes has been documented in pediatric patients (neonates, infants, and small children even < 2.5 Kg). The overall safety profile of TEE probe is quite favourable with a reported incidence of complications is about 1-3%. However, insertion of the TEE probe can induce vagal and sympathetic reflexes such as hypertension or hypotension, non-sustained ventricular and supraventricular tachyarrhythmias or bradyarrhythmias [3rd degree heart block], and even angina and myocardial infarction. We hereby document a repeated and fatal intraoperative VF precipitated by TEE probe in a 2-year-old, 10 kg paediatric patient diagnosed with ostium secundum atrial septal defect (OS-ASD), supravalvular pulmonary stenosis (PS) and severe right ventricular (RV) dysfunction.
Regional analgesia in Cardiac anesthesia: Welcoming a new era in perioperative pain management.Soojie Yu MD1, Oscar D. Aljure MD21 Mayo Clinic Arizona, Department of Anesthesiology2University of Miami, Department of Anesthesiology, Division of Cardiovascular and Thoracic AnesthesiologyPoorly controlled post-operative pain can delay recovery and may increase the risk of morbidity in patients undergoing cardiac surgery. After surgery, the sternal incision is the most common source of pain. Historically, the mainstay for pain management in this population has been usage of narcotic analgesics but with the recognition that overprescription of opioids may be contributing to the opioid pandemic, an adoption of a multimodal approach for pain management has been gaining more popularity among institutions in the US. Neuraxial analgesia and anesthesia has been used in the past but its impact in hemodynamics added to the risk associated with heparinization and coagulopathy has limited its use in cardiac surgery. Newer regional anesthesia/analgesia methods utilizing ultrasound guidance are associated with lower risk of complications when compared to neuraxial approach. Regional blocks that cover post-sternotomy pain include transverse thoracic muscle plane (TTMP) block, parasternal block, pecto-intercostal fascial blocks (PIFB), and erector spinae plane blocks. Out of all these newer techniques, the number of published prospective double blinded studies are limited. A contributing factor to the difficulty finding literature for these type of blocks is the description of the technique by the authors. A good example is the TTMP block where the local anesthetic is deposited in the TTMP block is similar to the described approach for the parasternal nerve block[3, 4]. Nomenclature aside, Kar and Ramachandran showed there are few prospective randomized control studies published on newer non-neuraxial regional techniques for postoperative pain control after cardiac surgery.In this issue of the Journal of Cardiac Surgery, Zhang et al present a prospective double-blinded study that looks at TTMP blocks placed pre-incision for post-sternotomy pain control after induction of anesthesia. In their study, for their TTMP block, the technique defined by the authors deposits local anesthetic between the costal cartilage and the transversus thoracis muscle as described similarly in other reports .Zhang and collaborators described on their study a significantly lower consumption of intraoperative opioids in the intervention group, that goes in hand with prior studies that have shown similar results when the block is performed after induction of anesthesia[6, 7]. In a study by Padala et al, patients who received blocks pre-incision had decreased fentanyl administration intraoperatively compare to patients who received the block prior to sternotomy closure. In Zhang’s study, the block group had faster extubation times, decreased pain scores up to 24 hours after surgery and decreased post-operative opioid administration. The block group also had improved quality of sleep after extubation which can enhance recovery and decrease risk of delirium.While regional blocks are very effective as shown by Zhang et al, a common issue is the short duration of the analgesic effects. Studies based on patient satisfaction have shown that the majority of patients continue to have mild to moderate sternotomy pain especially with movement and coughing up to post-operative day three or later. Whether the block was placed post-induction or prior to sternal closure, Padala’s study showed timing of placement of regional block did not seem to affect the total opioid requirement nor the pain scores for up to 24 hours postoperatively. Another study by Lee and collaborators, evaluated if the administration of Liposomal Bupivacaine would prolong the analgesic effect of the regional block. This formulation of bupicaine can have analgesic effects up to 72 to 96 hours. In the study, the parasternal intercostal block was placed just before sternotomy closure. Overall pain scores up to 72 hours postoperatively were significantly lower when utilizing a linear mixed effects model at a 5% significance level in the Experal group compare to the placebo group. Opioid administration though was not significantly different overall nor at individual time points up to 72 hours post-operatively.In this article, Zheng discusses the placement of a continuous infusion catheter as compared to a single shot block as an option to prolong the analgesic effects of the TTMP block. On a similar study, Ueshima, et al placed bilateral catheters after performing a TTMP block in two patients undergoing a median sternotomy. These catheters were administering intermittent and on demand boluses of levobupivacine for two days postoperatively. Both patients did not require any additional analgesics. A limitation for this technique is that the catheters were placed after induction of general anesthesia and this could not be feasible in all cardiac surgeries with median sternotomy. The internal mammary artery (IMA) and vein courses through the TTMP therefore administration of local anesthetic or placement of a catheter could be an issue in patients undergoing coronary artery bypass grafting with IMA harvesting.TTMP blocks are relatively quick and easy to place but complications which include pneumothorax, local anesthetic allergy, infection  and injury to the internal mammary artery and vein can occur. One particular study showed tissue plane separation after the TTMP block that did not affect directly the ability to harvest the IMA nor did it have any obvious effect on the IMA. In this study, Zheng had a very low incidence of complications adding to the safety profile of this block in cardiac surgery.Another popular technique that has been recently described that also targets the anterior intercostal nerves is the pecto-intercostal fascial block (PIFB) also called parasternal intercostal nerve block (PINB). For PIFB, local anesthetic is deposited between the pectoralis major and intercostal muscles making the location more superficial to TTMP block. The more superficial location potentially decreases the risk of pneumothorax while still providing post-sternotomy pain control. Similar to TTMP blocks, patients who received PIFB had decreased pain scores but the amount of opioid consumption was not significant decreased compared to placebo control. There has not yet been a study published comparing TTMP to PIFB for post-sternotomy pain control and risk of complications.In this issue of the Journal of Cardiac surgery, Zheng adds supporting evidence to the use of the newer non-neuraxial regional techniques as a feasible, practical option for the management of postoperative pain control in patients undergoing open cardiac surgery. This study adds to the growing evidence that TTMP blocks cover median sternotomy pain which is the main source of pain in post-cardiac surgery patients. The TTMP blocks are safe, easy to perform in the operating room after anesthesia and the incidence of complications is very low as reported in other studies. Limitations exist with TTMP blocks which include the relative short duration of analgesia. More studies will be needed to evaluate the continuous infusion of local anesthetic or other supplemental regional techniques to prolong the beneficial effects of this block.1. Mueller, X.M., et al., Pain location, distribution, and intensity after cardiac surgery. Chest, 2000. 118(2): p. 391-6.2. Kar, P. and G. Ramachandran, Pain relief following sternotomy in conventional cardiac surgery: A review of non neuraxial regional nerve blocks. Ann Card Anaesth, 2020. 23(2): p. 200-208.3. Del Buono, R., F. Costa, and F.E. Agro, Parasternal, Pecto-intercostal, Pecs, and Transverse Thoracic Muscle Plane Blocks: A Rose by Any Other Name Would Smell as Sweet. Reg Anesth Pain Med, 2016. 41(6): p. 791-792.4. Fujii, S., Transversus thoracis muscle plane block and parasternal block. Reg Anesth Pain Med, 2020. 45(4): p. 317.5. Ueshima, H. and H. Otake, Where is an appropriate injection point for an ultrasound-guided transversus thoracic muscle plane block?J Clin Anesth, 2016. 33: p. 190-1.6. Cardinale, J.P., et al., Incorporation of the Transverse Thoracic Plane Block Into a Multimodal Early Extubation Protocol for Cardiac Surgical Patients. Semin Cardiothorac Vasc Anesth, 2020: p. 1089253220957484.7. Padala, S., et al., Comparison of preincisional and postincisional parasternal intercostal block on postoperative pain in cardiac surgery. J Card Surg, 2020. 35(7): p. 1525-1530.8. Ranjbaran, S., et al., Poor Sleep Quality in Patients after Coronary Artery Bypass Graft Surgery: An Intervention Study Using the PRECEDE-PROCEED Model. J Tehran Heart Cent, 2015. 10(1): p. 1-8.9. Lahtinen, P., H. Kokki, and M. Hynynen, Pain after cardiac surgery: a prospective cohort study of 1-year incidence and intensity.Anesthesiology, 2006. 105(4): p. 794-800.10. Lee, C.Y., et al., A Randomized Controlled Trial of Liposomal Bupivacaine Parasternal Intercostal Block for Sternotomy. Ann Thorac Surg, 2019. 107(1): p. 128-134.11. Ueshima, H. and H. Otake, Continuous transversus thoracic muscle plane block is effective for the median sternotomy. J Clin Anesth, 2017. 37: p. 174.12. Ueshima, H. and H. Otake, Ultrasound-guided transversus thoracic muscle plane block: Complication in 299 consecutive cases. J Clin Anesth, 2017. 41: p. 60.13. Khera, T., et al., Ultrasound-Guided Pecto-Intercostal Fascial Block for Postoperative Pain Management in Cardiac Surgery: A Prospective, Randomized, Placebo-Controlled Trial. J Cardiothorac Vasc Anesth, 2021. 35(3): p. 896-903.
Molecular diagnosis is an essential means to detect pathogens. The portable nucleic acid detection chip has excellent prospects in places where medical resources are scarce, and it is also of research interest in the field of microfluidic chips. Here, the paper developed a new type of microfluidic chip for nucleic acid detection where stretching acts as the driving force. The sample entered the chip by applying capillary force. The strain valve was opened under the action of tensile force, and the spring pump generated the power to drive the fluid to flow to the detection chamber in a specific direction. The detection of COVID-19 was realized on the chip. The RT-LAMP amplification system was adopted to observe the liquid color in the detection chamber to decide whether the sample tested positive or negative qualitatively.
Fishbones migrated into surrounding tissues is relatively unusual. We present two cases of patients' migratory fish bones into the retropharyngeal space and hypopharynx. All fishbones were removed without complications. Early diagnosis of migratory fishbone and therapeutic management are essential for optimal patient survival.