Objectives: We determined the clinical and imaging features of patients with severe COVID-19 that were associated with survival. Methods: Sixty-seven patients hospitalised with severe laboratory-confirmed COVID-19, were consecutively enrolled. Clinical data, blood measurements and chest computed tomographic (CT) scans were analyzed. Results: We compared the findings between 39 survivors and 28 non-survivors. At admission, although there were no differences in white blood cell (WBC) and platelet (PLT) counts, there was an increase of WBC, neutrophil, platelet distribution width and mean platelet volume with a marked decrease of lymphocyte, monocyte, eosinophil and PLT in non-survivor group on their last day compared to survivors (P < 0.05). Non-survivors had higher ratios of peak creatinine(P<0.05) and peak lactate dehydrogenase (LDH) (P<0.05). Compared to survivors, the incremental rate of total lesion area, ground-glass opacity (GGO) area and consolidation area on CT scans was increased in non-survivors (P<0.05).The deceleration rate of total lung volume was greater in non-survivors than survivors(P<0.05). Using the univariate survival analysis, the following were predictive of non-survival: time from admission to peak of D-dimer (D2D)<16 days , initial pro-BNP>319.0 pg/ml, peak procalcitonin (PCT) ≥0.19 ng/ml, peak creatinine>96.5 μmol/l ,peak alkaline phosphatase (ALP)>81.5 u/l, median time from admission to peak ALP<18 days, the acceleration rate of total lesional area> -11.5 cm3 /day, incremental rate of GGO area> 2.4 cm3 /day and the acceleration of consolidation area> 2.3 cm3 /day. Conclusion: Hematological counts, serum analytes and radiological indicators, the latter assessed by artificial intelligence, are robust predictors of survival outcome in COVID-19.

Species dispersal patterns and population genetic structure can be influenced by large geographical features and habitat fragmentation. The Qinling Mountains are a major east-west mountain range and they are also the northernmost habitat of wild Cymbidium faberi in China. However, the impact of the Qinling Mountains and habitat fragmentation in the areas on genetic variation of C. faberi at population level is still poorly understood. Here, genetic analysis of C. faberi in the Qingling Mountains was conducted based on two chloroplast DNA sequences of 271 samples in 15 locations. Hierarchical analyses of molecular variance (AMOVA) and mantel test indicated that most of the genetic variance was within populations, genetic distance between populations was correlated with the geographical distance but not strong (mantel r = 0.505, P = 0.011). Spatial analysis of molecular variance (SAMOVA) indicated that the FCT reached the maximum value at K = 2 and then decreased, which supported a two-group genetic structure. Furthermore, the Extended Bayesian Skyline Plot revealed that the estimates of effective population size of C. faberi were under demographic equilibrium in the past but an apparent decline going from approximately 1 Ma towards the present. Moreover, we found that the genetic diversity of C. faberi in fragmented landscape was lower compared to continuous ones. Therefore, we concluded that the habitat fragmentation has restricted the gene flow of C. faberi by disrupting seed dispersal. Our findings may provide helpful references for understanding how humans shape the genetic structure and the importance of conserving wild orchids.

Letter to the editor

We report a case of community acquired pneumonia due to Streptococcus pyogenes to remind physicians be aware of pernicious characteristics of S. pyogenes and be prepared to provide proper prevention strategies to improve prognosis.

Plant roots exert critical controls over microbial decomposition, but climate change factors may alter these effects. Yet, the direction and magnitude of interactive climate change effects, as well as the underlying mechanisms, remain unclear. Here we show evidence from a field experiment demonstrating that climate change factors strengthen root controls over litter decomposition in a semi-arid grassland. While plant roots significantly increased soil microbial biomass, they suppressed microbial activities, C-cycling enzymes and litter decomposition. Both precipitation reduction and warming reduced decomposition regardless of the root presence, but precipitation increase stimulated decomposition only in the absence of roots, suggesting that plants outcompete microbes for water and constrain microbial activities. Together, warming-enhanced plant competition for water, combined with N-suppression of microbes, may provide a unique mechanism through which moderate increases in precipitation, warming and N inputs interactively enhance root controls over microbial decomposition, thereby facilitating soil C sequestration in the water-limiting grasslands.

Even though antimicrobial-resistant bacteria have begun to be detected in wildlife, raising important issues related to their transmission and persistence of clinically important pathogens in the environment, little is known about the role of these bacteria on wildlife health, especially on endangered species. The Brazilian merganser (Mergus octosetaceus) is one of the most threatened waterfowl in the world, classified as Critically Endangered by the International Union for Conservation of Nature. In 2019, a fatal case of sepsis was diagnosed in an 8-day-old Brazilian merganser inhabiting a zoological park. At necropsy, major gross lesions were pulmonary and hepatic congestion. Using microbiologic and genomic methods, we identified a multidrug-resistant (MDR) extended-spectrum β-lactamase (ESBL) CTX-M-8-producing Escherichia coli (designed as PMPU strain) belonging to the international clone ST58, in celomic cavity, esophagus, lungs, small intestine and cloaca samples. PMPU strain harbored a broad resistome against antibiotics (cephalosporins, tetracyclines, aminoglycosides, sulfonamides, trimethoprim, and quinolones), domestic/hospital disinfectants, and heavy metals (arsenic, mercury, lead, copper, and silver). Additionally, the virulence of E. coli PMPU strain was confirmed using a wax moth (Galleria mellonella) infection model, and it was supported by the presence of virulence genes encoding toxins, adherence factors, invasins and iron acquisition systems. Broad resistome and virulome of PMPU contributed to therapeutic failure and death of the animal. In brief, we report for the first time a fatal colibacillosis by MDR-ESBL-producing E. coli in critically endangered Brazilian merganser, highlighting that besides colonization, critical priority pathogens are threatening wildlife. E. coli ST58 clone has been previously reported in humans, food-producing animals, wildlife, and environment, supporting broad adaptation and persistence at human-animal-environment interface.

Background: This study aims to determine the hemodynamic performance of double valve prostheses and its effects on long term outcomes of tricuspid regurgitation(TR) following double valve replacement (DVR). Methods: Between January 2014- September 2017, all patients undergoing concomitant aortic and mitral valve replacement with or without concomitant tricuspid valve repair at the same center were reviewed. All patients were divided into three groups according to interventions tricuspid valve(TVI), that is no-tricuspid annuloplasty(TAP), tricuspid ring annuloplasty and tricuspid de-vega annuloplasty (TDVA).Results: The study included 179 patients, of whom 52% were women(with mean age 51.7±13.7 years). Of 179 patients, 100 were in the no-TAP group, 39 were in the ring annuloplasty group and 40 were in the TDVA group. There was no statically significant difference among the groups with regard to potential complications, in-hospital mortality and the survival rates. The degree of TR decreased with TVI. The rates of moderate and severe TR were significantly lower in in the ring annuloplasty group (P = 0.04 and 0.004). Female gender (OR = 4.0, 95%CI: 1.0-15.5, p = 0.05) and preoperative TR degree(OR = 2.9, 95%CI: 1.1-7.3, p = 0.01) were an independent predictors for the development of postoperative severe TR. Conclusion: Although the degree of postoperative TR varies according to whether to perform a TVI, DVR can be safe due to low operative mortality independently from TVI. The rates of moderate and severe TR were significantly lower in the ring annuloplasty group and female gender was an independent risk factor of TR progression.

There is increased interest in the potential of tree planting to help mitigate flooding using nature-based solutions or natural flood management. However, many publications based upon catchment studies conclude that, as flood magnitude increases, benefit from forest cover declines and is insignificant for extreme flood events. These conclusions conflict with estimates of evaporation loss from forest plot observations of gross rainfall, throughfall and stem flow. This study explores data from existing studies to assess the magnitudes of evaporation and attempts to identify the meteorological conditions under which they would be supported. This is achieved using rainfall event data collated from publications and data archives from studies undertaken in temperate environments around the world. The meteorological conditions required to drive the observed evaporation losses are explored theoretically using the Penman-Monteith equation. The results of this theoretical analysis are compared with the prevailing meteorological conditions during large and extreme rainfall events in mountainous regions of the UK to assess the likely significance of wet canopy evaporation loss. The collated dataset showed that Ewc losses between approximately 2 and 38% of gross rainfall (1.5 to 39.4 mm d-1) have been observed during large rainfall events (up to 118 mm d-1) and limited data for extreme events (> 150 mm d-1). Event data greater than 150 mm, where duration was not reported, showed similarly high percentage evaporation losses. Theoretical estimates of wet-canopy evaporation indicated that, to reproduce these high losses, relative humidity and the aerodynamic resistance for vapour transport needed to be within an envelope of approximately 90 to 97.5% and 0.5 to 2 s m-1 respectively. Surface meteorological data during large and extreme rainfall events in the UK suggest that conditions favourable for high wet-canopy evaporation are not uncommon and indicate that significant evaporation losses during large and extreme events are possible but not for all events and not at all locations. Thus the disparity with the results from catchment studies remains.

Despite sinus valsalva aneurysm of a well-known pathology, its presence as a cardiac tumor with the RA compression is rare. A 64-year-old man was accidentally identified with a cardiac tumor during the survey of atrial fibrillation. The initial echocardiography and chest computed tomography (CT) displayed a huge mass at right atrium. Surprisingly, the operative findings diagnosed a sinus valsava aneurysm. This case highlights the diagnostic challenges of a huge sinus valsava aneurysm which mimics an intra-cardiac tumor.

Background & Aim: Traumatic aortic injury (TAI) is a life-threatening condition. We present cases of 7 patients with TAI limited at the isthmus. Case description: Seven patients with TAI were treated between January 2015 and December 2018; TAI was caused by motor vehicle crashes in all cases. The patient characteristics and the post-operation data were collected and analyzed. We performed thoracic endovascular aortic repair (TEVAR) for five patients during their first hospitalization using Relay Plus® (Japan Lifeline, Japan). While patient 6 underwent TEVAR 5 years after the injury, patient 7 was recommended conservative care because she had dementia. Since most of these patients did not have a history of hypertension, they were not on antihypertensive medications after TEVAR. Conclusions: In cases of TAI, intervention by TEVAR in the acute phase improves the patient’s quality of life. Additionally, TEVAR is expected to prevent TAI from enlarging to form an aortic aneurysm.

There is a renewed interest in the Renin-angiotensin system (RAS) as the coronavirus SARS-CoV2 enters the human body through the host ACE2 receptor. The infection is associated with down regulation of ACE2 leading to the imbalance in the RAS. We provided mechanistic insight on immunopathology of COVID-19 with respect to innate immune activation and ensuing adaptive immune response resulting in production of viral antigen-specific antibodies. The mini-review tries to drive home the anti-inflammatory role of ACEI/ARBs as an attractive treatment option in hypertensive or heart failure patients suffering from COVID19. The hypothesis is based on the available evidence of favorable immuno-mechanistic and clinical outcome data. The review tinkers with the immuno-mechanistic pathway with a probable role type I IFN response in case of SARS-CoV2, which is not yet clear. The review interconnected the role of principal players involved in RAS such as Angiotensin-converting enzyme (ACE), ACE2, decapeptide angiotensin I (ANG I), octapeptide angiotensin II (ANG II), heptapeptide angiotensin-(1–7), nonapeptide angiotensin-(1–9), ACE inhibitors (ACEI), AT1R blockers (ARBs) with respect to cardiovascular physiology and pathology.

A document by Shivaahnee Raveenthiran. Click on the document to view its contents.

A document by somayeh noori Hekmat. Click on the document to view its contents.

We have explored the structural and energetic properties of a series of RMX3–NH3 (M=Si, Ge; X=F, Cl; R=CH3, C6H5) complexes using density functional theory and low-temperature infrared spectroscopy. In the minimum-energy structures, the NH3 binds axially to a halogen, while the organic group resides in equatorial site about the metal. Remarkably, the primary mode of interaction in several of these systems seems to be hydrogen bonding (C-H–N), rather than a tetrel N-M interaction. This is particularly clear for the RMCl3–NH3 complexes, and analyses of the charge distributions of the acid fragment corroborate this assessment. We also identified a set of metastable geometries in which the ammonia binds axial to the organic substituent. Acid fragment charge analysis also provide a clear rationale as to why these configurations are less stable than their R-equatorial counterparts. In matrix-IR experiments, we see clear evidence of the minimum-energy form of CH3SiCl3–NH3, but analogous results for CH3GeCl3–NH3 are less conclusive. Computational scans of the M-N distance potentials for CH3SiCl3–NH3 and CH3GeCl3–NH3, both in the gas phase and bulk dielectric media reveal a great deal of anharmonicity, and a propensity for condensed-phase structural change.

The symbiotic bacteria associated with honeybee gut have likely transformed from a free-living or parasitic lifestyle, through a close evolutionary association with the insect host. However, little is known about the genomic mechanism underlying bacterial transition to exclusive adaptation to the bee gut. Here we compared the genomes of bee gut symbionts Apibacter with their close relatives living in different lifestyles. We found that despite of general reduction in the Apibacter genome, genes involved in amino acid synthesis and monosaccharide detoxification were retained, which was likely beneficial to the host. Interestingly, the microaerobic Apibacter species have specifically preserved the NAR operon encoding for the nitrate respiration pathway which in contrast, is absent from the related non-free-living microaerobic pathogenic relatives. The NAR operon is also conserved in the cohabiting bee microbe Snodgrasella, but with a differed structure. This convergence implies a crucial role of respiration nitrate reduction for microaerophilic microbiomes to colonize bee gut epithelium. Genes involved in lipid, histidine and phenylacetate degradation are partially lost in Apibacter, possibly associated with the loss of pathogenicity. Antibiotic resistance genes were only sporadically distributed among Apibacter species, but condensed in their pathogenic relatives. Collectively, this study advanced our understanding of genomic transition underlying specialization in bee gut symbionts.

Summary Objective: Endoplasmic reticulum aminopeptidase 1 (ERAP1) is known to participate in the pathogenesis of ankylosing spondylitis (AS) cooperated with HLA-B27. This study aimed to evaluate the relationship between promoter methylation and mRNA levels of ERAP1 and AS. Methods: The DNA methylation level of 100 AS patients and 100 health controls (HCs) were tested using targeted bisulfite sequencing assay. Besides, the mRNA level of 20 AS patients and HCs was measured used quantitative real-time reverse transcription-polymerase chain reaction to verify the results of DNA methylation. Results: The methylation levels of two CpG islands containing 31 loci in ERAP1 promoter were measured. ERAP1_1 (P < 0.001) and ERAP1_2 (P < 0.001) islands were significantly hyperrmethylated in AS patients compared with healthy controls. Correspondingly, the mRNA level was significantly lower in AS patients. The ROC curve analysis reported the sensitivity, specificity and area under curve were 0.717, 0.737 and 0.779 of differential methylated CpG loci of ERAP1 for AS diagnosis. Besides, we also found that the methylation level was associated with the family history, non-steroidal anti-inflammatory drugs use, X-ray classification and clinical manifestations. Conclusions: Our study demonstrated that the ERAP1 gene is significantly hypermethylated in AS patients, which is verified by the lower mRNA level of AS patients. Our findings suggested that aberrant methylation of ERAP1 promoter may take part in the pathogenesis of AS and can be considered as diagnostic tool and therapeutic target of AS.

Objective: To investigate the early recognition of ureteral injury in gynecological operation and improve the technique of endoscopic placement of ureteral stents. Design:Retrospectively analyze the clinical and prognostic data of iatrogenic ureteral injuries in gynecological operations in our institution from 2013 to 2019. Setting: Shunde Hospital, Southern Medical University. Population: Women with iatrogenic ureteral injury due to gynecological surgery. Methods: To analyze the causes, clinical manifestations, early identification methods and surgical techniques for repairing ureteral injuries of patients with iatrogenic ureteral injuries. Main outcome measures:Time to discover ureteral injury by different methods and success rate of ureteral injury repair. Results:13 cases were delayed diagnosis, of which 4 cases were confirmed by pelvic drainage urinary creatinine detection at 6.50 ± 3.11 days after operation, and 9 cases were diagnosed by pyelography after 36.8 ± 12.36 days after operation. Ureteroscopy + retrograde ureteral stent placement were the first choices. Seven patients (53.85%) were successful. Three patients who failed repair operation immediately used cis-percutaneous nephroscopy combined with retrograde ureteroscopy to successfully place ureteral stents. Among the 10 patients who successfully placed stents, 9 patients were cured except for 1 case of renal insufficiency. Conclusions: The liquid creatinine test for recognition of ureteral injury after gynecological surgery is effective.For some serious ureteral injuries, percutaneous renal anterograde combined with retrograde ureteroscopy and ureteral stent placement can improve the success rate of intubation.

Survivorship care is a major area of focus in the holistic management of childhood cancer with current knowledge and information almost exclusively from high-income countries. In this review, we summarize the state of scientific knowledge, service delivery, advocacy initiatives and research efforts in this field in India. 21 single centre studies published till date (20 in the last decade) confirm some of the well-documented issues in childhood cancer survivors and also highlight the high prevalence of hepatitis B and hepatitis C infection in our survivors. Heterogeneity in methodology, outcome metrics and quality precludes drawing further conclusions and the ongoing multicenter Indian Pediatric Oncology Group study would address this. Besides the usual model of follow-up clinics in hospital settings, innovative models of service delivery led by not-for-profit organisations are being developed. Advocacy initiatives driven by survivors and support groups are also underway. All of these portend a promising future.

Background : Wiskott Aldrich syndrome (WAS) is a rare disease and hematopoietic stem cell transplant (HCT) is considered the treatment modality of choice for WAS. Methods : We conducted a cross-sectional analysis on the Kids’ inpatient database and compared hospitalization rates, complications and healthcare utilizations in the transplant and non-transplant arms. Results. : Of the 396 patients with WAS admitted between 2006-2012, 114 underwent transplant and 269 did not. The non-transplant arm included older children, female patients and more African Americans. Death rates, income and payer source were similar in both arms, however the total charge for each admission was higher in the transplant arm. ED visits were similar but elective admissions were more in the transplant arm. Length of stay was prolonged in the transplant arm. When comparing morbidities, lymphomas, ulcerative colitis and autoimmune complications of WAS were seen only in the non-transplant arm. Conclusions : Our study shows that transplant is the largest contributor to healthcare utilization in WAS patients. We noted a change in practice moving away from splenectomy in WAS patients. We identified healthcare disparities based on race and socioeconomic status and found that only a few centers across the nation manage WAS, suggesting need for wider resources for this very rare disease.

Objective: Children presenting in diabetic ketoacidosis (DKA) may require a central venous catheter (CVC) to adequately manage their supportive care. These children are at increased risk of developing CVC-associated venous thromboembolism (VTE), but no predictive indicators have been identified to foretell which patients are at greatest risk. We analyzed demographic and laboratory data from children with DKA undergoing CVC placement to determine which patients may be at increased risk of CVC-associated VTE. Design: A retrospective chart review was conducted for patients aged 0-5 years admitted with DKA, CVC placement, and possible subsequent VTE development over ten years at a single institution. Reported demographic and laboratory variables were compared amongst patients that developed VTE and those that did not using Mann-Whitney rank sum tests. CVC-associated VTE incidence was also compared between children with DKA and all other patients undergoing CVC placement. Results: We identified 149 children with DKA, 17 underwent CVC placement, and 9/17 (52.9%) developed CVC-associated VTE. Length of hospital stay was the only significant difference between those that developed VTE and those that did not. Also, the prevalence of catheter associated VTE in DKA (1.7%) was significantly higher than that for CVC placement for any other reason (p<0.001). Conclusions: Careful consideration for CVC placement and minimizing duration of catheter use is suggested in this high risk population. Given the extremely high risk and lack of identifiable predictors, anticoagulation prophylaxis should be strongly considered for all young children with DKA requiring CVC placement.

Objectives: The recent outbreak of COVID-19 has culminated in the unbearable negative life outcomes for all. The study explored the perceived psychological distress and consequent health outcomes caused by COVID-19. Design: The Narrative Thematic Analysis design was used. Methods: A heterogeneous sample of 18 participants (12 males and 6 females) responded about their experiences of the recent outbreak of COVID-19. The data were collected through a telephonic semi-structured interview that was analyzed through the Thematic Analysis Method.  Results: Four themes were generated: perceived psychological distress, lower social support, enhanced religious practices and enhanced negative health outcomes. Extreme anxiety, panic experiences, insecurity, helplessness, hyper-vigilance and negative attributions represented the psychological distress while decreased social interactions and imposed social distancing characterized the perceived social support. Increased reliance on myths, divine interpretations and faith in God showed religious practices. Decreased hunger, insomnia, headache, breathing problems and palpitation were ill-health outcomes.Conclusions: The epidemic was sudden, unknown and fatal that shaped the nature and extent of perceived psychological distress, social support and religious practices. The first two may have caused negative health outcomes while the religious practices maintained equilibrium among the rest three. Immediate trans-disciplinary efforts for the effective prevention, treatment and promotion of the affected people are recommended. KeywordsCOVID-19; pandemic; psychological distress; health consequences; social support; religious practices; narrative thematic analysis.

We suggest PLAID,APLAID and FCAS3 have to be considered as same diseases,because of our long-term clinical experiences and genetic results in six patients.Small proportion of CVID patients are also PLAID/APLAID/FCAS3 patients and all these have disease-causing-mutations in PLCG2-genes,so it may be better to define all of them as “PLCG2 deficiency”.

Introduction There is currently a lack of available data clearly addressing whether the proportion of young patients diagnosed with head and neck cancer (HNC) within the U.S. has increased over the last several decades in comparison to other age cohorts. This study attempts to elucidate any trends in oral cavity, oropharynx, larynx and hypopharynx cancer age distribution in the United States population from 1975-2016. Unlike previous studies, this paper does not track incidence, but rather reports proportional changes of prevalence within age cohorts over time. Methods This is a retrospective chart review centered on data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). Each decade interval from 1975-2016 displays the proportion of HNC patients, classified by primary tumor subsite, within each age cohort. Results Mean age at diagnosis increased for three of the four HNC evaluated. Oropharyngeal cancer was the only subsite to demonstrate an overall proportional increase, mainly in middle age (40-59 years) patients. Cancers of the oral cavity were the only subset to show a true increase in the proportion of young (0-39 years) patients. When stratifying by gender, the proportion of young patients in female HNC cases is higher than the proportion of young male HNC cases. Conclusion Overall, this study demonstrates an increased proportion of older HNC patients that is consistent with the aging population. Oral cavity is the only cancer to demonstrate a true increase in the proportion of young patients, likely from the increased incidence of young women diagnosed with this cancer. Case reports citing more young patients becoming diagnosed with other types of HNC are not currently supported by the data. Lastly, the increased proportion of middle-age patients with oropharyngeal cancer likely reflects the increase in HPV-related cancers.

To the Editor:We enjoyed reading the case, authored by Janus and Hoit, of a 67-year-old woman with a subarachnoid hemorrhage (SAH) who presented with three different variants of takotsubo (TT).[i] We congratulate the authors on their interesting contribution to the literature. We would like to share some comments and questions on the chronology and management of the events between the first two episodes, which occurred a few days apart. Although fascinating, this is not the first case of TT with a rapidly evolving pattern. We previously described a case of mid-ventricular takotsubo which replaced apical ballooning in 6 hours.[ii] A recent meta-analysis showed that almost 80% of TT recurrences exhibit a ballooning pattern different from the first presentation.[iii] In this regard, regional cardiac sympathetic innervation remodeling or denervation could hypothetically justify why the same territory is usually spared from further relapses. Even though images were not provided, the authors stated that “echocardiographic wall motion abnormalities quickly resolved after each acute stressor”. One could therefore argue that this was not a case of multiple TT variants during the same episode, as noted by Madias,iii but rather an example of early recurrences. Additionally, if cardiac innervation remodeling were responsible for the different locations of the ballooning, we believe that the change in pattern would have taken longer to manifest. This would not support the observation of two distinct ballooning patterns emerging within days, let alone hours.i, ii In this case, a short-term change from the mid-ventricular to apical pattern could be reasonably explained by different β adrenergic-receptor (β-AR) subtype downregulation. We know that norepinephrine can downregulate β1-AR after a few hours. Beta1-ARs are markedly lower on biopsied patients with acute TT compared to healthy controls,[iv] whilst in the same study β2-ARs expression—which is predominant in the apical and mid-ventricular segments and thought to be involved in typical takotsubo pathogenesis[v]—was equivalent to normal. Thus, the sequence of events could be interpreted as a relative local β2 prevalence due to dynamic β1 downregulation (β1:β2 mismatch), following a base:mid-ventricle, and ultimately a mid-ventricle:apex progression. What do the authors think about this theory? Is it possible that multi-faceted presentations might simply be under-recognized? Should this be the case, how do they think we could better understand this phenomenon in a noninvasive fashion? Could dobutamine stress echocardiography have utility to identify areas of β-AR downregulation and sympathetic denervation? It would also be interesting to know more about the patient’s medical therapy. Did she receive nonselective β-blockers, such as labetalol or carvedilol, usually prescribed after SAH? If so, this might indicate that β-blockers do not prevent recurrences,[vi] but rather create a maladaptive imbalance in regional β1:β2 distribution favoring early relapse(s), as this case suggests.References[i] Janus SE, Hoit BD. The three faces of takotsubo cardiomyopathy in a single patient. Echocardiography. 2020 Jan;37(1):135-138. doi: 10.1111/echo.14560. Epub 2019 Dec 16.[ii] Casavecchia G, Zicchino S, Gravina M, et al. Fast 'wandering' Takotsubo syndrome: atypical mixed evolution from apical to mid-ventricular ballooning. Future Cardiol. 2017 Nov;13(6):529-532. doi: 10.2217/fca-2017-0018. Epub 2017 Oct 12.[iii] Madias JE. Comparison of the first episode with the first recurrent episode of takotsubo syndrome in 128 patients from the world literature: Pathophysiologic connotations. Int J Cardiol. 2020 Mar 3. pii: S0167-5273(20)30215-1. doi: 10.1016/j.ijcard.2020.03.003.[iv] Nakano T, Onoue K, Nakada Y, et al. Alteration of β-Adrenoceptor Signaling in Left Ventricle of Acute Phase Takotsubo Syndrome: a Human Study. Sci Rep 8, 12731 (2018). https://doi.org/10.1038/s41598-018-31034-z.[v] Paur H, Wright PT, Sikkel MB, et al. High levels of circulating epinephrine trigger apical cardiodepression in a β2-adrenergic receptor/Gi-dependent manner: a new model of Takotsubo cardiomyopathy. Circulation. 2012 Aug 7;126(6):697-706. doi: 10.1161/CIRCULATIONAHA.112.111591. Epub 2012 Jun 25.[vi] Santoro F, Ieva R, Musaico F, et al. Lack of efficacy of drug therapy in preventing takotsubo cardiomyopathy recurrence: a meta-analysis. Clin Cardiol. 2014 Jul;37(7):434-9. doi: 10.1002/clc.22280. Epub 2014 Apr 3.