Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder that clinically manifests with sudden death and progressive heart failure. Moreover, thyroid dysfunction is associated with increased cardiovascular morbidity and mortality risks. Therefore, this study aimed to clarify whether thyroid hormones could serve as an independent predictor of adverse events in patients with HCM.The cohort consisted of 782 patients with HCM who had thyroid hormones baseline data and were admitted to the Affiliated Hospital of Jiaxing University. Patients were divided into two groups according to serum levels of free triiodothyronine (fT3): the normal fT3 and low triiodothyronine (T3) syndrome groups. Low T3 syndrome was defined as fT3 < 2.43 pmol/L with a normal thyroid‐stimulating hormone (TSH) level. Patients whose TSH levels were abnormally high or abnormally low were excluded from this study. The primary endpoint was the occurrence of sudden cardiac death (SCD) events, and the secondary endpoint was a composite of worsening heart failure (WHF) events, including heart failure death, cardiac decompensation, hospitalization for heart failure, and HCM‐related stroke. The Kaplan–Meier and Cox regression were performed for the survival analysis.p = .02 and log‐rank p = .001, respectively). Furthermore, multivariate Cox regression analysis demonstrated that low T3 syndrome is a strong predictor of SCD events and WHF events .After a median follow‐up of 52 months, 75 SCD events and 134 WHF events were recorded. The Kaplan–Meier survival curves showed that the cumulative incidence of SCD events and WHF events were significantly higher in patients with low T3 syndrome  syndrome is highly prevalent among patients with hypertrophic cardiomyopathy and was independently associated with an increased risk of sudden cardiac death events and worsening heart failure events. Each participant provided informed consent before enrollment.2.2Patients' demographics, medical history, laboratory findings, echocardiographic data, prescribed medications at discharge, and New York Heart Association (NYHA) classification were obtained and verified from the Nanjing Haitai Medical Information System (version 3.0). Additionally, clinical and ultrasound parameters that show a strong association with the risk of SCD in the HCM population, including a family history of sudden death, unexplained syncope, nonsustained VT, MLVWT, and LVOTO, were obtained.2.3n = 42), subclinical hyperthyroidism , overt hypothyroidism , overt hyperthyroidism , and TSH using an enhanced chemiluminescence method . In our laboratory, the reference intervals of thyroid hormones and TSH were as follows: fT3: 2.43–6.02 pmol/L, fT4: 9.01–19.03 pmol/L, and TSH: 0.36–4.95 μIU/mL. We first excluded patients with hypothyroidism or hyperthyroidism based on the combination of TSH and fT4 serum levels: subclinical hypothyroidism  and the low T3 syndrome group (fT3 < 2.43 pmol/L). There was no patient whose TSH values were normal with fT3 values elevated (>6.02 pmol/L) in the present study.2.4The participants were followed up through subsequent outpatient visits, telephone contact, and WeChat every 3 months for the first year and then every 6 months for the remaining period after discharge. Survival data and heart failure events were recorded by trained cardiologists at the Affiliated Hospital of Jiaxing University. Those who were lost to follow‐up were censored at their last interview.The primary endpoint of this study was SCD events, defined as sudden death due to cardiac causes, ICD shocks, or recorded cardiac arrest.2.5t‐test. Categorical data were summarized as percentages, and differences were compared using the χ2 test. Moreover, Fisher's exact test was applied when assumptions for the χ2 test were invalid. Survival analysis was performed using Kaplan–Meier survival curves, and log‐rank tests were employed to compare differences between patients with normal fT3 and low T3. Univariate and multivariate proportional analyses were used using the Cox proportional hazard regression model to examine the relationship between low T3 syndrome and adverse events during a median follow‐up of 52 months.Continuous data were presented as mean ± standard deviation and analyzed by the Student p < .05 was considered statistically significant. All statistical analyses were conducted using IBM SPSS Statistics for Windows version 24.0 (IBM Corp.).The stepwise model selection method was used for prognostic variable selection. The significance level required for an entry criterion was <0.20, and the exit probability was >0.05. Moreover, a forced entry strategy was employed, and a priori established SCD risk factors were entered into the multivariate model. As a result, variables that entered the final model for SCD events include unexplained syncope, family history of sudden death, MLVWT > 30 mm, nonsustained VT on Holter monitoring, LVOTO, and depression. After the prespecified model was developed, other confounding variables  were retested based on a sensitivity analysis to verify their influence on effect estimates. Multivariate models were established individually for SCD events and WHF events in a similar approach. Crude and adjusted hazard ratios (HRs) were calculated with 95% confidence intervals (CIs). 33.1The study cohort included 782 patients with HCM aged 49.9 ± 13.1 years, of whom 58.4% were men. Among these, 112 (14.3%) were in the low T3 syndrome group, and 670 (85.7%) were in the normal fT3 group. Moreover, 741 participants (94.8%) completed a median follow‐up of 52 months, and both groups exhibited comparable dropout rates , and 134 developed WHF events   was significantly increased in patients with low T3 syndrome than in the normal fT3 group. Table p < .01; HR = 2.62, 95% CI: 2.03–3.49, p < .001, respectively). Two multivariate models were constructed individually to investigate the effects of low fT3 levels on SCD events and WHF events. After adjusting for traditional risk factors and depression, multivariate Cox regression demonstrated that low T3 syndrome remained an independent predictor of SCD events and WHF events (adjusted HR = 1.53, 95% CI: 1.13–2.24, p < .01; HR = 3.87, 95% CI: 2.91–4.98, p < .001, respectively; Table The Kaplan–Meier survival curves indicated that the cumulative incidence of SCD events (log‐rank 4To our knowledge, this study is the first to clarify the potential association between low T3 syndrome and adverse events in patients with HCM. Our study finds that low T3 syndrome comprises 14.3% of euthyroid patients with HCM. It shows that low fT3 levels are associated with an increased risk of SCD events and WHF events. In our earlier studies, patients with depression and HCM had more than double the risk of SCD events.Thyroid dysfunction is commonly seen in cardiovascular diseases and serves as a strong predictor of subsequent adverse outcomes. Two decades ago, Iervasi et al.Currently, clinical studies evaluating the effect of thyroid hormones on patients with HCM are limited. To date, only the study by Zhang et al.The potential mechanisms linking low fT3 levels and adverse outcomes have not been completely elucidated; however, several interpretations have been proposed. Generally, both T3 and T4 are crucial for cardioprotection and constitute the major active forms of thyroid hormones; however, T3 is the only bioactive hormone for cardiomyocytes, whereas T4 is believed to be the precursor of T3.Despite the encouraging findings, this study has several limitations. First, this was a single‐center observational study, which limits the generalizability to other populations and could be further confirmed by multicenter studies. Second, thyroid status was measured only at baseline and may have changed in a longer follow‐up period. Third, patients who were prescribed medications that may influence thyroid function were excluded; consequently, the effect of thyroid treatment on clinical outcomes was not explored in this study. Finally, since no intervention was adopted to increase the serum fT3 levels in their normal range, studies should investigate whether fT3 supplements would benefit patients with low T3 syndrome and improve their prognosis in the future. Concurrently, the strengths of our study include a large sample size, a well‐characterized HCM population, comprehensive data on thyroid function, detailed cardiac assessment, an observational study with few patients lost to follow‐up, and adjustment for the traditional risk factors in the multivariate model.5Our study demonstrated that low T3 syndrome is highly prevalent among patients with HCM and was associated with SCD events and WHF events. Routine assessment of fT3 levels may provide risk stratification in this population.The authors declare no conflict of interest.Supporting information.Click here for additional data file.


Prevotella sp and Faecalibacterium prausnitsii. Increased SCFAs, changes in gut microbiota composition, function and metabolic profile following 12 weeks of adalimumab suggest that targeting SCFAs may be considered a potential biomarker to be evaluated as a complementary protective factor or as a diagnostically relevant signal in HS.Altered gut microbiota composition has been observed in individuals with hidradenitis suppurutiva (HS) and many other inflammatory diseases, including obesity, type 1 and type 2 diabetes. Here, we addressed whether adalimumab, a systemic anti‐inflammatory therapy, may impact the microbiota biochemical profile, particularly on beneficial metabolites such as short‐chain fatty acids (SCFAs). We conducted an observational single‐arm pilot trial to assess gut microbiota composition by 16S rRNA gene sequence analysis and to detect metabolite signatures by gas chromatography in stool samples from participants with HS prior to and 12 weeks after commencing adalimumab therapy. HS individuals that better responded to adalimumab treatment showed a shift in the composition and function of the gut microbiota with significantly increased SCFA acetate and propionate compared to age, gender and BMI‐matched healthy controls. A positive correlation was observed between propionate with  Principal component analysis (PCA) illustrates a shift towards control samples.  compared to healthy controls at W0, but the differences between healthy controls and HS at Week 12 were largely absent  showed a significant increase in alpha diversity similar to healthy controls  associated with increased faecal SCFAs, induced Tregs, reduced IgE levels and the numbers of mast cells, eosinophils and basophils.Prevotella sp, Faecalibacterium prausnitsii, Bifidobacterium adolescentis, Colinsella aerofaciens and Ruminococcus bromii are well documented.Prevotella spp and propionate concentrations in HS after adalimumab treatment are consistent with previous documentation of Prevotella spp being important in disease activity of HS.Bifidobacteria and Ruminococcus have been associated with accumulation of visceral adiposityPositive correlations observed between the SCFAs and 3.1The study included a small sample size and limited follow‐up of the study. Without a placebo control group, this study could not determine whether any of the changes observed are caused by the therapy or only associative. A follow‐up placebo‐controlled trial powered is needed to determine causal effects from adalimumab through the production of anti‐inflammatory SCFAs in a larger study and longer follow‐up period of intervention to better determine any impact on clinical response.44.1Adult participants with a confirmed clinical diagnosis of HS made by a consultant dermatologist were invited to participate in the study. The South Western Sydney Local Health District Human Research Ethics Committee provided ethical approval for this study . Written informed consent was obtained from all participants in line with the Declaration of Helsinki. Exclusion criteria included participants under 18 years of age, current or previous treatment with a biologic agent, topical or oral anti‐microbial therapy. Clinical data including age, gender, BMI, smoking status, height, weight, disease severity as measured by Hurley Staging, abscess, nodule and tunnel counts were recorded at baseline. All HiSCRs were performed by the same clinician experienced in HS clinical scoring. Two individuals achieved HiSCR 75, but none achieved HiSCR 100. Healthy control participants were recruited from the general population and were age, gender and BMI matched to HS participants.4.2Subcutaneous adalimumab therapy was provided at the FDA‐approved dose . All participants underwent appropriate screening for HIV, hepatitis B, hepatitis C and quantiferon gold testing for latent tuberculosis prior to enrolment in the study. All participants continued on adalimumab therapy as a standard of care after completing involvement in the trial. Healthy controls were not exposed to adalimumab therapy.4.3n = 6) were collected at baseline  and Week 12 of adalimumab therapy. Faecal samples from healthy controls (n = 6) were taken at baseline and Week 12 time points. All faecal samples were collected at the time of clinical examination. Faecal samples were immediately frozen at −80°C until processing.Faecal samples (~1 g) from participants with HS . Stool samples were mixed with internal standards solution and centrifuged. One hundred microliters of supernatant was filtered through the 100 μm mesh filters and transferred to the glass insert GC vials. Samples were analysed on an Agilent 7890A gas chromatograph (Agilent Technologies). Peaks were detected with a flame ionization detector at 210°C and identified and quantitated against calibration standards over the range of 0 to 400 mM. Intra‐assay CVs were 14.2%, 11.8% and 10.3% for acetate, propionate and butyrate, respectively.4.5Total DNA was extracted using the QIAamp DNA stool mini kit (Qiagen). Briefly, the stool was homogenized in Buffer ASL using a tissue disperser  for 1 min and processed following the manufacturer's protocol. Amplification of DNA samples was performed by Micromon, Monash University, by targeting the V3‐V4 region of bacterial 16S rRNA gene using forward primer 5′‐ CCTACGGGNGGCWGCAG‐3′ and reverse primer 5’‐GACTACHVGGGTATCTAATCC‐3′. The PCR reaction was carried out in 25 μl volumes containing 5 ng/μl DNA template, 1 μM of each primer and 12.5 μl of 2X KAPA HiFi HotStart ReadyMix (Kapa Biosystems). The following PCR conditions were used: The following PCR conditions were used: initial denaturation at 95°C for 3 min, followed by 25 cycles consisting of denaturation (95°C for 30 s), annealing (55°C for 30 s), and extension (72°C for 30 s) and a final extension step at 72°C for 5 min. PCR products were purified using AMPure XP beads (Beckman Coulter) and sequenced using Illumina Miseq sequencer. For microbiota bioinformatics, a total of 3 161 460 raw paired‐end reads were obtained from the Illumina MiSeq amplicon sequencing, targeting the V3‐4 region of the 16S rRNA gene. The sequences were denoised, quality filtered and defined into Amplicon Sequence Variants (ASVs) using the dada2 R package.4.6p < 0.05 was considered statistically significant. All statistical analysis for clinical associations was undertaken using Prism (8.4.2).The statistical significance of the alpha diversity indices between different timepoints was derived using Wilcoxon signed rank test. The same test was also conducted to compare the expression of SCFAs across timepoints. For beta diversity, the data were first transformed into Aitchison distance, and the differences between the bacterial composition across timepoints and subject groups (i.e. control and HS) were compared using Factorial, Repeated Measure and Pairwise PERMANOVA separately (vegan R and pairwiseAdonis R).Conceptualization: GDC, JAW, JWF, EMM. Data Curation: SAS, AT, JWF, EMM. Formal Analysis: EMM, JWF, SB, CCW. Funding Acquisition: JAW, GDC, Investigation: SAS, ATT, SB, CCW. Methodology: JAW, GDC, JWF, EMM. Project Administration: JAW, GDC, JWF, EMM. Resources: JAW, GDC, EMM. Software: JWF, EMM, CCW. Supervision: GDC, JAW, JWF, EMM. Validation: JWF, EMM, CCW. Visualization: JWF, CCW, EMM. Writing–Original Draft: JWF, EMM. Writing Review and Editing: SDS, AT, JAW, GDC, SB, CCW, EMM, JWF.Funding was provided via an unrestricted educational grant from Sun Pharma. Sun Pharma had no role in collecting, analysing or interpreting data, writing the report or deciding to submit the report for publication.JWF has conducted advisory work for Janssen, Boehringer‐Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, Abbvie and UCB. He has participated in trials for Pfizer, UCB, Boehringer‐Ingelheim, Eli Lilly and CSL, and received research support from Ortho Dermatologics and Sun Pharma. CCW provides data science consultation for Asian Microbiome Library, Singapore.Figure S1. No significant difference was seen between faecal SCFA concentrations in participants with HS at baseline when stratified by the presence of epithelialized tunnels or smoking status (Assessed using Wilcoxon Rank Sum test with Bonferroni Adjustment for multiple comparisons).Click here for additional data file.Figure S2. Significant elevation in faecal Butyrate found at W12 of adalimumab therapy in individuals with epithelialized tunnels compared with those without epithelialized tunnels .Click here for additional data file.


In December 2019, the Botswana government expanded free antiretroviral therapy (ART) to include non‐citizens. We evaluated the impact of this policy change on antenatal care (ANC), antiretroviral therapy coverage and adverse birth outcomes.The Tsepamo Surveillance study collects data at up to 18 delivery sites in Botswana. We compared outcomes in citizens and non‐citizens living with HIV before and after antiretroviral therapy expansion to non‐citizens. Adverse birth outcomes included preterm delivery (PTD) <37 weeks, very preterm delivery (VPTD) <32 weeks, small for gestational age (SGA) <10th percentile, very small for gestational age (VSGA) <3rd percentile, stillbirth and neonatal death. Log‐binomial regression models were constructed to generate risk ratios.p<0.001), and became more similar to citizens (96.0% post‐expansion). Non‐citizens receiving any antenatal antiretroviral therapy increased from 65.5% pre‐expansion to 89.9% post‐expansion (p < 0.001), also more similar to citizens (97.2% post‐expansion). Infants born to non‐citizens with singleton gestations in the pre‐expansion period had significantly greater risk of PTD , VPTD  and neonatal death , but reduced SGA risk  compared with citizens. Post‐expansion, greater declines in most adverse outcomes were observed in non‐citizens, with largely similar outcomes between non‐citizens and citizens. Non‐significant differences were observed for non‐citizenship in PTD , VPTD , SGA , VSGA , stillbirth  and neonatal death .From August 2014 to September 2021, 45,576 (96.5%) citizens and 1513 (3.2%) non‐citizens living with HIV delivered; 954 (62.9%) non‐citizen deliveries were before the antiretroviral therapy expansion, and 562 (37.1%) were after. Non‐citizen ANC attendance among pregnant people living with HIV increased from 79.2% pre‐expansion to 87.2% post‐expansion (Following the expansion of free antiretroviral therapy to non‐citizens, gaps narrowed in ANC and antiretroviral therapy use in pregnancy between citizens and non‐citizens living with HIV. Disparities in adverse birth outcomes were no longer observed. Non‐citBeginning in December 2019, all non‐citizens were allowed access to free antiretroviral therapy in Botswana . To impl22.1This secondary analysis of data from the Tsepamo study included birth outcomes that occurred from up to 18 maternity sites at government facilities throughout Botswana. Before July 2018, data collection occurred at eight government maternity wards and accounted for approximately 45% of all births in Botswana . Data on2.2Extracted data from maternal obstetric records included demographic information, maternal medical history, ANC information, inpatient care during labour and delivery, medical diagnoses made in pregnancy, adverse birth outcomes, maternal HIV status and HIV treatment information. Citizenship status is determined with the use of national identity cards (Omang) for citizens, and non‐citizens present their country of origin documentation when accessing healthcare services. Infant information included gestational age, birth weight, sex and admission to the neonatal unit. All diagnoses included in the analyses were recorded as documented by the treating physician or midwife. The date of the last menstrual period was used to estimate gestational age. If the date of the last menstrual period was unknown, healthcare providers used second‐ or third‐trimester ultrasound or fundal height measurement to determine the gestational age. Maternal obstetric records for all births were reviewed at the time of discharge and clinical data from the obstetric cards were transcribed into a REDCap database , 23.2.3All adverse birth outcomes were determined by delivery nurses at the maternity wards and the data were abstracted from their antenatal records , 23. Adv2.4p‐Values were computed using two‐sided tests at the α  =  0.05 significance level. All statistical analyses were performed using RStudio version 1.4.1717 software.Proportions of maternal demographics, ANC attendance, HIV status, antiretroviral therapy uptake and adverse birth outcomes were determined and compared between citizens and non‐citizens living with HIV before and after the December 2019 antiretroviral therapy expansion to non‐citizens. Based on subject‐matter knowledge, identified covariates for our adjusted analyses included maternal age, education, occupation, parity and marital status. As only citizens were permitted access to free antiretroviral therapy before December 2019, pregnant citizens living with HIV were selected as the primary referent group to demonstrate the impact of reduced barriers to antiretroviral therapy on the health of pregnant non‐citizens living with HIV and their infants. Sensitivity analyses were conducted to explore potential associations between citizenship status and adverse birth outcomes among pregnant people without HIV, to account for the impact of COVID‐19 on adverse birth outcomes, to account for multiple pregnancies and to evaluate any potential impact due to missing data. Log‐binomial regression models for the primary and sensitivity analyses were used to obtain crude and adjusted risk ratio (aRR) estimates with 95% confidence intervals. 2.5Intuitional approval for this study was provided by the Health Research and Development Committee in Botswana and the institutional review board of Harvard T.H. Chan School of Public Health in Boston, Massachusetts. As data were collected anonymously and via chart abstraction, maternal consent was waived.3From August 2014 to September 2021, there were 204,130 live deliveries and stillbirths recorded in the Tsepamo birth surveillance study .Among citizens, 137,814 (70.4%) deliveries occurred in the pre‐antiretroviral therapy expansion period and 58,025 deliveries (29.6%) in the post‐antiretroviral therapy expansion period .There were 7607 deliveries among non‐citizens during the entire study period, with 4711 (61.9%) deliveries in the pre‐antiretroviral therapy expansion period and 2896 deliveries (38.1%) in the post‐antiretroviral therapy expansion period. In the pre‐antiretroviral therapy expansion period, the median age for pregnant non‐citizens was 29 years  compared with 28 years  in the post‐antiretroviral therapy expansion period. Compared with the pre‐antiretroviral therapy expansion period, non‐citizens in the post‐antiretroviral therapy expansion period were less likely to be married (50.3% vs. 46.4%), but more likely to be primiparous (23.1% vs. 25.9%), to deliver at a rural maternity site (31.0% vs. 49.7%), and to have at least one ANC visit (81.6% vs. 87.5%) , whereas the proportion of citizens with unknown HIV status generally remained unchanged (0.5% vs. 0.4%) (p = 0.02)  , which narrowed the gap with citizens (97.2%). After December 2019, the proportion of non‐citizens and citizens receiving DTG‐based antiretroviral therapy was similar (42.0% vs. 44.3%).Several characteristics related to HIV and antiretroviral therapy differed between the pre‐ and post‐antiretroviral therapy expansion eras, and are highlighted below. The proportion of non‐citizens with unknown HIV status decreased in post‐antiretroviral therapy policy expansion period (6.2% vs. 1.3%)  Figure . For non) Figure . In comp) Figure . After t3.3n = 926) than to citizens with HIV   compared with citizens , and there were greater overall declines in adverse birth outcomes among singletons born to non‐citizens  , 47. HowThe strengths of our study included a large sample size of pregnant people, well‐defined adverse birth outcomes, and detailed ANC and antiretroviral therapy information. Additionally, our sensitivity analyses support our findings Tables  and S2. 5In conclusion, following the expansion of free antiretroviral therapy to non‐citizens in Botswana, there were temporal improvements in HIV diagnoses, antiretroviral therapy uptake in pregnancy with a DTG‐based regimen and adverse birth outcomes. These improvements were noted in non‐citizens living with HIV but not among other exposure groups, suggesting that antiretroviral therapy may play a role in narrowing previous gaps in health outcomes. While Botswana is fortunate to have a mature antiretroviral therapy programme with very high coverage, these findings may also be applicable in other regions where barriers exist to improving antiretroviral therapy uptake in pregnancy, adding urgency to efforts towards universal access to modern antiretroviral therapy regimens.There are no reported competing interests.CF, DE and RS designed the study and performed the analysis. RS, MD, GM, JM, TS, TG, MM, SL and JM helped to oversee and operate the Tsepamo study and provided data for this study. CF, DE and RS drafted the manuscript; RZ, MD, SL, JM and TS reviewed and contributed to the development of the manuscript, and all authors read and approved the final manuscript.The study was supported by the National Institute of Child Health and Human Development (NICHD/NIH) (R01HD080471 and R01HD095766).Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.


Focal nodular hyperplasia (FNH) is a noncirrhotic tumor that is the second most benign tumor, accounting for 2% of all pediatric liver tumors.A 13‐year‐old Japanese girl developed a nodular hepatic lesion that was undetectable on ultrasonography 12 months ago. She was initially treated as an outpatient for obesity at 8 years of age. At 10 years old, she had obesity (obesity index 53.3%) and fatty liver confirmed by ultrasonography. Abdominal ultrasonography had been performed annually since then.Her medical history included successful treatment for Kawasaki disease with high‐dose immunoglobulin therapy. She had also occasionally received leukotriene antagonist for bronchial asthma as a 1‐year‐old and had received midodrine hydrochloride because of orthostatic dysregulation since she was 10 years old. No bleeding tendency was observed. Her parents had bronchial asthma and her brother had childhood obesity, but there was no family history of liver disease.On physical examination, her height was 158.8 cm (+0.8 SD) and weight was 81.6 kg (+2.9 SD). Her obesity index and body mass index were 61.0% and 32.4, respectively, indicating obesity. Her abdominal circumference was 113 cm and blood pressure was 112/70 mmHg. She had acanthosis nigerians on her neck and axilla and striae distensae on her abdomen, buttocks, and thighs.Blood examination indicated moderately increased aminotransferase levels due to fatty liver  and hyperinsulinemia with a normal HbA1c (5.2%), normal fasting plasma glucose (96 mg/dl), and elevated immunoreactive insulin level (45.2 mIU/ml). Her FIB‐4 index based on her age, AST and ALT levels, and platelet cell count  was 0.14, which was not indicative of liver fibrosis. Hepatitis B and C markers  and tumor markers  were within normal ranges.Ultrasonography revealed a hypoechoic nodule with clear boundaries in S7 and uniform internal and enhanced posterior echoes Figure . PerflubFocal nodular hyperplasia is most common in women aged 30–50 years with no liver disease, and often accompanies abnormal vascular morphology. Pediatric patients with FNH often have a history of anticancer drugs and radiation therapy.A definitive diagnosis of FNH is based on (1) absence of liver damage, (2) spoke‐wheel appearance of the vascular structure and a central scar on imaging, and (3) pathological findings of central scar‐like fibrous tissue, increased cell density, and hyperplasia.The Central Medical Journal has reported 73 cases of FNH and two of FNH‐like lesions in children <18 years since 1985, but no FNH or FNH‐like lesions in children with fatty liver. Epidemiological data also suggested that being overweight or obese was associated with liver cancer.We encountered a girl with an FNH‐like lesion and fatty liver. Follow‐up is necessary because the lesion appeared within 1 year and she has a fatty liver and hyperinsulinemia.M.M. was responsible for managing the patient, review of the clinical chart, perusing the potentially relevant literature, and drafting the initial manuscript, and conceiving the case report. M.M. and Y.N. were responsible for planning and implementing diagnostic imaging. Y.N., K.S., and T.I. supervised the draft manuscript. All authors read and approved the final manuscript.The authors declare no conflict of interest.Written informed consent was obtained from the patient's guardian for the publication of this manuscript.


Novel point‐of‐care assays which measure urine tenofovir (TFV) concentrations may have a role in improving adherence monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). However, further studies of their diagnostic accuracy, and whether results are associated with viraemia and drug resistance, are needed to guide their use, particularly in the context of the global dolutegravir rollout.We conducted a cross‐sectional evaluation among PLHIV receiving first‐line ART containing tenofovir disoproxil fumarate at enrolment into a randomized trial in two South African public sector clinics. We calculated the diagnostic accuracy of the Abbott point‐of‐care immunoassay to detect urine TFV compared to liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). We evaluated the association between point‐of‐care urine TFV results and self‐reported adherence, viraemia ≥1000 copies/ml and HIV drug resistance, among people receiving either efavirenz or dolutegravir‐based ART.p<0.001) and medium‐term (p = 0.036) self‐reported adherence. Overall, 44/124 (35.5%) had viraemia, which was associated with undetectable TFV in those receiving efavirenz  and dolutegravir . However, in those with viraemia while receiving efavirenz, 8/27 (29.6%) had undetectable urine TFV, compared to 11/17 (64.7%) of those receiving dolutegravir. Drug resistance was detected in 23/27 (85.2%) of those receiving efavirenz and only 1/16 (6.3%) of those receiving dolutegravir. There was no association between urine TFV results and drug resistance.Between August 2020 and March 2022, we enrolled 124 participants. The median age was 39 (IQR 34–45) years, 55% were women, 74 (59.7%) were receiving efavirenz and 50 (40.3%) dolutegravir. The sensitivity and specificity of the immunoassay to detect urine TFV ≥1500 ng/ml compared to LC‐MS/MS were 96.1% (95% CI 90.0−98.8) and 95.2% (75.3−100.0), respectively. Urine TFV results were associated with short (Among PLHIV receiving ART, a rapid urine TFV immunoassay can be used to accurately monitor urine TFV levels compared to the gold standard of LC‐MS/MS. Undetectable point‐of‐care urine TFV results were associated with viraemia, particularly among people receiving dolutegravir.Pan‐African Clinical Trials Registry: PACTR202001785886049. ViraemiTenofovir disoproxil fumarate (TDF) is a key component of World Health Organization‐recommended ART and is used by over 95% of people receiving ART in LMICs , 4, therWhile several clinical trials are evaluating the impact of point‐of‐care urine TFV assays on HIV treatment outcomes , 12, 13,In this study, we aimed to evaluate the diagnostic accuracy of a point‐of‐care test to detect urine TFV at the manufacturer threshold of 1500 ng/ml, compared to the gold standard LC‐MS/MS. This threshold is estimated to classify 98% of people who took a TDF dose 24 hours ago as adherent, and 86% of those who last took a dose 96 hours ago as non‐adherent ) did not detect urine TFV in 1/8 (12.5%) with viraemia ≥1000 copies/ml, and detected urine TFV in 395/398 (99%) of those with viral suppression . Of the A case−control study within the ADVANCE trial in South Africa matched 139 participants, recently initiated on ART and with rebound viraemia, with 53 non‐viraemic controls . Sixty‐sAnother South African study, among 113 people with previous viraemia or treatment interruptions, found that among people with viraemia ≥400 copies/ml, 64.7% of those receiving dolutegravir/boosted protease inhibitors had an undetectable Abbott point‐of‐care urine TFV result, compared to only 4.8% among those receiving efavirenz. Only one person receiving efavirenz had undetectable urine TFV . SimilarThis is one of the first evaluations of the analytic performance of the Abbot point‐of‐care urine TFV assay, beyond the validation conducted as part of the assay's development . It is aOur findings provide further evidence supporting the use of point‐of‐care urine TFV immunoassays as objective indicators of adherence, and provide further insights into where they may be utilized in clinical practice. With widespread global TDF use, and recent data suggesting point‐of‐care urine TFV results are also associated with viraemia among people taking TFV alafenamide , the tes5Point‐of‐care urine TFV may be used to monitor ART adherence and predict viraemia, particularly in people receiving dolutegravir.Abbott provided the urine TFV assays at no cost. The authors have no other competing interests to declare.JD, PKD and NG conceived the study. RL, KG, PM and NS were responsible for laboratory testing. RL, YS, CCB and GH contributed to study design. MG developed the urine TFV assay. JD analysed the data and wrote the first draft of the manuscript. All authors critically reviewed and edited the manuscript and consented to final publication.This work is supported by grants from the Wellcome Trust PhD Programme for Primary Care Clinicians (216421/Z/19/Z), the University of Oxford's Research England QR Global Challenges Research Fund (0007365) and the Africa Oxford Initiative (AfiOx‐119). HIV drug resistance testing and drug concentration testing was funded by the National Institute for Health and Care Research (NIHR) Community Healthcare MedTech and In Vitro Diagnostics Co‐operative at Oxford Health NHS Foundation Trust (MIC‐2016‐018); GH, CCB and PT also receive funding from this award.The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The University of Oxford is the study sponsor. The funders and sponsor had no role in study design, manuscript submission, or collection, management, analysis or interpretation of study data.Supporting InformationClick here for additional data file.


CECR1  gene. Disease manifestations could be separated into three major phenotypes: inflammatory/vascular, immune dysregulatory, and hematologic; however, most patients presented with significant overlap between these three phenotype groups.The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessively inherited disease resulting from loss‐of‐function mutations in ADA2, formerly named We present a case of DADA2 deficiency with disease onset at 3 years old, not recognized till the age of 18 with severe gastrointestinal vasculitis and recurrent episodes of neutropenia associated with a new CECR1 mutation. The diagnosis of DADA2 is often delayed due to its pleiomorphic manifestations: vasculitis, immune dysregulation and variable hematologic involvement. Over the last few years, next‐generation sequencing has led to the detection of more than 50 monogenic autoinflammatory diseases,We report the fatal case of a female patient with a novel mutation for ADA2 deficiency who displayed isolated severe neutropenia for over 6 years before additional symptoms.3) with neutropenia (180/mm3) and elevated C‐reactive protein (CRP) (180 mg/L).The patient started experiencing recurrent bouts of oral aphthae and fever since the age of 3 years. Around the age of 10, she associated recurrent episodes of oligoarthritis in small and large joints with acute onset. Blood work during the attacks revealed leukopenia  and double‐stranded DNA ; thus, the diagnosis was switched to systemic lupus erythematosus (SLE), and she received a low dose of corticosteroids and hydroxychloroquine 200 mg/day daily.3) with neutropenia (up to 20/mm3) associated with inflammatory syndrome were noticed during the prolonged hospitalization.At the age of 17, she was admitted to an emergency department of a pediatric unit for spontaneous clostridial myonecrosis Figure . Fasciot3). Recurrent episodes of neutropenia (up to 700/mm3 leukocytes and 2 neutrophils/mm3) associated with inflammatory syndrome  were pointed out, requiring periodic administration of granulocyte‐colony‐stimulating factor 30 MU/0.5 mL daily for 3–5 days and moderate to high doses of corticosteroids with good response , mild hypogammaglobulinemia (IgG = 600 mg/dL), normal complement levels, and a slightly elevated ferritin (429 ng/mL). Screening was negative for antinuclear, antiphospholipid, antineutrophil cytoplasmic antibodies, and rheumatoid factor. Peripheral blood flow cytometry showed reversed CD4:CD8 ratios, natural killer cell lymphopenia and decreased peripheral B cells 0.28/mm. RecurreThoracoabdominal computerized tomography (CT) revealed an enterocutaneous fistula and important hepatosplenomegaly; no significant findings were noted on cerebral CT. Angiography could not be performed. Surgical excision of the enteroatmospheric fistula and of the ileocecal pouch was performed with slow to good recovery Figure .Many of her clinical features were pointing to Behcet's disease , even the presence of HLAB51. However, except for the steroids, no other immunosuppressive worked. Besides that, regular repeated episodes (every 2–3 weeks) of fever, inflammatory syndrome, and leukopenia with neutropenia were pointing to an autoinflammatory disease. Next‐generation sequencing revealed that the patient carried compound heterozygous mutations at positions 139 (exon 2) and 661_664 (exon 4) of the coding sequence of ADA2 , resulting, respectively, in amino acid substitution p.Gly47Arg and premature translational stop signal p.Ala221Glnfs*45 in ADA2. Thus, the patient was diagnosed with ADA2 deficiency based on the combination of the clinical picture: cutaneous manifestations , musculoarticular manifestations (arthritis), gastrointestinal manifestations , hematological manifestation  associated with recurrent fever and inflammatory syndrome and the biallelic mutation of ADA2. ADA2 activity could not be determined. To the best of our knowledge, the second variant was not described in the medical literature so far.Clostridium difficile colitis, and colonization of surgical wounds with Klebsiella and Pseudomonas. The clinical picture became even more complicated with an episode of acute interstitial edematous pancreatitis followed by a pancreatic pseudocyst of 6 cm.During hospitalization, she experienced multiple infectious episodes—recurrent 3), followed shortly by severe pancytopenia. Bone marrow biopsy showed 56% granulocytes, 7%–8% lymphocytes, 1%–2% plasmocytes, 3%–4% blasts, among them 12%–13% promyelocytes, and an increased number of activated macrophages with dense granules. Serum folate and vitamin B12 were normal, and ferritin was slightly elevated (782 ng/mL). Thus, we excluded hemophagocytic lymphohistiocytosis or myelodysplastic syndrome as possible causes. Rising procalcitonin levels (> 10 ng/dL) made sepsis a more plausible cause. Despite supportive treatment, broad‐spectrum antibiotics and antifungal therapy, intravenous immunoglobulins, corticosteroids, erythrocytes, and thrombocyte transfusions, the patient's overwhelming hyperinflammatory syndrome progressed over the next week. This was followed by respiratory deterioration requiring mechanical ventilation and multiorgan failure, which led to the patient's demise the following day. We searched the literature for adverse reactions cited after the initiation of biological treatment; however, severe infections were uncommon following the initiation of anti‐TNF therapy.3, median 490/mm3), and hypogammaglobulinemia nonresponsive to corticosteroids and intravenous immunoglobulins.When she was stable , anti‐TNF‐⍺ therapy with etanercept 25 mg was started. Anti‐TNF is the treatment of choice in ADA2 deficiency, being usually safe and effective for most manifestations, although it is often not sufficient for severe hematological phenotypes. At 48 h after the first administration, she developed progressive severe thrombocytopenia (up to 9000/mmOur case highlights the need for early testing in patients with severe inflammatory and hematological manifestations that recur and cannot be controlled with usual therapies and also reports a new mutation possibly associated with severe hematological phenotype of DADA2.Delia Nicoară: Writing—original draft. Cristina Niță: Data curation; methodology; visualization. Ana Stanilă: Investigation; validation. Alexandru Martiniuc: Investigation; validation. Laura Popa: Investigation; validation. Eliana Petrescu: Investigation; validation. Mihaela Bătăneant: Investigation; methodology; resources. Ruxandra Ciofu: Data curation; visualization. Adriana Guriță: Funding acquisition; investigation; supervision. Radu Tabăcaru: Funding acquisition; investigation; validation. Ruxandra Ionescu: Supervision; visualization. Laura Groșeanu: Conceptualization; data curation; visualization; writing—review and editing. All authors read and approved the final manuscript.The authors declare no conflict of interest.Local ethics approval was obtained. Written institutional informed consent was obtained from the patient. Written informed consent to publish the case and pictures were obtained from the parents after the patient died.


Finally, we offer the current challenges that need to be addressed for advanced K‐based batteries.Potassium (K)‐based batteries are viewed as the most promising alternatives to lithium‐based batteries, owing to their abundant potassium resource, lower redox potentials (−2.97 V vs. SHE), and low cost. Recently, significant achievements on electrode materials have boosted the development of potassium‐based batteries. However, the poor interfacial compatibility between electrode and electrolyte hinders their practical. Hence, rational design of electrolyte/electrode interface by electrolytes is the key to develop K‐based batteries. In this review, the principles for formulating organic electrolytes are comprehensively summarized. Then, recent progress of various liquid organic and solid‐state K + electrolytes for potassium‐based batteries. First, the key design principles and applications of organic liquid electrolyte in various battery systems are discussed. Then the research status of ionic liquid, gel/polymer, and solid electrolyte are summarized and evaluated. Finally, this review discusses the challenge of various electrolyte/electrode interfaces and puts forward promising research direction and opportunities in the future. This review mainly focuses on the recent progress of various liquid organic and solid‐state K Potassium (K)‐base batteries and sodium (Na)‐based batteries provide an alternative solution, owing to abundant reserves of K and Na . Moreover, the price of potassium and sodium carbonate  are considerably less expensive than Li2CO3. Since both K and Na do not alloy with aluminum, the aluminum foil is employed as the anodic current collector, replacing the costly and dense copper in lithium‐based batteries.The clean and sustainable energies could relieve the environmental pollution and fossil fuel crisis. However, these generated energies are intermittent depending on the geographic location and weather conditions. Therefore, it is necessary to seek a large‐scale energy storage systems (ESSs) for efficient storing and outputting the variable energy . Rechargeable batteries are the most efficient ESS to store and convert chemical energy into electrical energy. Lithium‐based batteries, as one typical rechargeable battery, have dominated the markets of portable electronic devices, and electric vehicles in the past few decades.1 Neve+ electrode (−2.93 V vs. E0) than that of Na (−2.71 V vs. E0), which guarantee high‐energy density. In addition, it has been confirmed the voltage of the K/K+ in propylene carbonate (PC) is lower than Li/Li+. Then, K‐based batteries could realize high‐rate performance due to the high diffusion coefficient of K+ ions. Although potassium has the large atomic radius (1.38 Å), K+ has the smallest Stokes’ radius (3.6 Å) in propylene carbonate (PC) solvents owing to weak coulombic interactions of K+. The first‐principles molecular dynamics simulations also have proved that the diffusion coefficient of K+ in EC is three times than that of Li+. In addition, it also revealed that K+ has the lowest solvation energy of (397.5 kJ mol−1) in ethylene carbonate (EC), which favor a higher rate capability compared to Li+ and Na+. Furthermore, K+ could reversibly intercalate/deintercalate into or from graphite, which is the most used anode material for lithium‐ion batteries. On the basis of the advantages mentioned above, K‐based batteries are most possible alternatives to lithium‐ions batteries (LIBs).However, potassium‐based batteries potentially offer numerous advantages over sodium‐based batteries. First, K‐based batteries are expected to provide a higher work voltage than sodium‐ion battery (SIB). The lower redox potential of K/K alloy negative, transition metal oxides/chalcogenides and K or Na‐K alloy anode have intensively studied. Among the anode candidates, K metal has higher work voltage and specific capacity (≈687 mAh g−1). Moreover, K metal anodes can enable the application of potassium‐free cathodes battery systems, such as, potassium metal batteries (KMBs), potassium superoxide (K‐O2), and potassium‐sulfur batteries (K‐S). Cathode materials for K‐ion batteries involve four categories: Prussian blue (PB) and its analogues, layered transition metal oxides, organic redox‐active molecules, and polyanionic compounds. However, high‐compatible electrolyte and optimization of interfaces are still in its infancy.Recently, considerable progress has been achieved on K‐based batteries. Specifically, these strategies are focused on designing high‐performance cathode and anode materials, electrolyte, interface engineering, and electrode/battery configurations, etc. At present, vast electrode materials have used in K based batteries. For anode materials, carbon‐based materials,9 allo Up to now, the reported electrolytes for K‐based batteries can be divided into liquid and solid‐state electrolyte  applications. Recently, KPF6 and KFSI salts are also widely investigated in PIBs. However, one of the main concerns of such organic electrolyte is narrow electrochemical stability window, leading to some undesirable side reactions at electrode/electrolyte interfaces along with the formation of solid electrolyte interphase (SEI). The ideal SEI could prevent further side‐reactions, and promoting uniform K+ diffusion, which is a recognized prerequisite for a metal or insertion/conversion anode. However, there are still several major problems for organic electrolytes, such as, lack of suitable salts and additives, unstable SEI, serious side reactions, high flammability, and K dendrites growth. To address the problems, various electrolytes such as, inorganic electrolytes, ionic liquid (IL) electrolyte, gel polymer, and polymer electrolytes are proposed. Nevertheless, these novel electrolytes suffer from low ionic conductivity at room temperature, and their electrochemical performance for K‐based batteries are almost blank. In brief, the booming development of K‐based batteries will depend on the exploration of matching electrolytes, as well as, in‐depth understanding of interface.In battery systems, an electrolyte should possess high ionic conductivity, compatible interface, high chemical stability, large electrochemical stability window, ability to inhibit dendrites, and high electronic resistance.15 Up e Figure . As for + electrolytes in Section + exists and transports across cells, how the interphases are formed and structured at both electrode surfaces. In Sections 2 batteries, from liquid and solid‐state electrolytes. Considering K metal as the counter/reference/work electrode K based batteries, the issue of dendrites growth and unstable K/electrolyte interface are critical needed. Finally, future perspectives and directions are put forward for follow‐up researches.In this review, we begin with common formulation and design principle of K22.1+ based electrolytes electrolyte, liquid electrolytes, and solid‐state electrolytes. Liquid electrolytes involve organic system, aqueous system, gel polymer, and ionic liquid system. Solid‐state electrolytes contain inorganic solid electrolyte (ISE) and polymer system. In this review, only organic, polymer gel, ionic liquid, polymer, or inorganic electrolytes are covered, leaving out aqueous electrolytes.Currently, there are two main types of K Most organic potassium electrolytes are based on solutions of one or more potassium salts in mixed solvents, with a small fraction of functional additives. The solvents have two sides. On the one hand, organic solvents with high dielectric constants and low viscosity enable faster ion mobility and better interfacial wetness. On the other hand, the active reaction, the high volatilization and flammability of organic solvents pose a major safety hazard. Thus, the major challenge of organic electrolytes design is the option of solvents, additives and appropriate concentration. Accordingly, it is of great significance to reduce the amount of solvent for batteries. Gel polymer electrolytes (GPEs) could be considered as the special variation of liquid‐type electrolytes, in which only a small fraction of polymer is employed as the mechanical host, and essentially swollen by liquid electrolytes. Although they show improved properties in ionic conductivity and compatibility, the growth of dendrites still remained the serious safety concerns. Ionic liquid (IL) electrolytes exist as liquid state, and consist of organic anions and cations, coupled with soluble K salt. The opposite ions are achieved by the thermal melting rather than solvation by solvent. They are demonstrated to possess excellent electrochemical and thermal stability, low volatility, and fire resistance. However, IL electrolytes have lower K+ conductivity at room temperature (RT) because of higher viscosity and charge transfer numbers.As observed, organic electrolytes are the most widely used electrolytes in Li/Na/K‐based batteries, owing to their unsurmountable advantages, such as, high ionic conductivity, good compatibility with electrodes.18 Mos However, Integration of highly ionic conductive solid electrolytes (SSEs) in solid state batteries remains a challenge, mainly due to the high impedance of the electrolyte/electrode interface. Moreover, at present, both polymer and inorganic electrolytes show low K+ conductivity, and electrochemical performance in K‐based batteries is scarce.Different from organic electrolytes, solid‐state electrolytes exhibit high safety, thermal stability, and mechanical strength, which make they are potential frontier with great potential in academia and industry.15 How2.2+, and electrochemical stability of electrolytes. In this section, we describe fundamental properties , how K+ exists and moves in bulk electrolyte, how the interphases are formed and structured at both electrode surfaces, and how improve the electrochemical stability window of electrolytes.In battery systems, electrolytes work an important role in the performance of batteries. The rate capability, cycle life, coulombic efficiency (CE) of batteries are closely related to the ion transport, solvation effect of K2.2.1η, to facilitate ion transport) exhibits high ionic conductivity for their solutions. However, these two parameters are contradictory. Thus, mixed solvents of either high dielectric permittivity or low viscosity are needed. The cyclic carbonates like propylene carbonate (PC) or ethylene carbonate (EC) and linear carbonates, such as, dimethyl carbonate (DMC), diethyl carbonate (DEC), and ethyl methyl carbonate (EMC), to date, are the most promising electrolytes for alkalis battery applications. So far, in such mixed solvents, optimize ion conductivity reach as high as 5–10 mS cm−1. Okoshi et al. evaluated 27 organic solvents, in terms of geometric structure, desolvation energy, and interaction energy of K+, and concluded that the interaction between K+ and solvents played a dominant role in mobility. The solubility of salt is related with its lattice energy, and low dissociation energy promotes the dissolution of K salt. The effects of common K salts on transport properties of electrolyte have been explored by Hosaka et al. Figure 6, KFSI, KTFSI, KClO4, and KBF4 in PC. The KPF6, KFSI, KTFSI completely dissolved, while vast salt powder visually remained in the KClO4 and KBF4 mixtures. The 0.5 M KFSI, KTFSI, and KPF6 in PC solutions showed high ionic conductivities in the scope of 5–7 mS cm−1, while KClO4 and KBF4 exhibited lower. Generally, K salts with large size of anions have a high solubility, such as, KFSI and KTFSI. Thus, KFSI based electrolytes displayed higher conductivity than that of KPF6 solutions in various solvents, for instance, EC/DEC, PC, and dimethyl ether (DME). Electrolyte concentration is also a key strategy for regulating ionic conductivity. In the past for a long time, 1 M is considered as the most optimal concentration at which the ion conductivity is maximal.Ionic conductivity is a fundamental measure for electrolyte, which quantifies how fast ions move between cathode and anode, and in part determines the power output of a cell. The ionic conductivity of electrolyte is relevant to the dielectric properties and viscosity of the solvent, the interaction between solvent and cations, solubility of the salt, and concentration. As well known, solvent with high dielectric constant  and low viscosity ( mS cm−1.21 Okot+) is beneficial for improving rate performance. It had proved that even modest improvements in t+, for example, to t+ ≈ 0.7, would be beneficial to quickly charge the battery. However, the ionic conductivity obtained by electrochemical impedance spectroscopy is the apparent conductivity, which involves the contribution of both cations and anions, and few studies accurately measure the true transference number. Compared to Li+ , K+ possesses higher transference number (0.43) in 1 M KFSI in EC/DEC = 1:1, due to low charge density of K+. In binary molten electrolyte LiCl/KCl system, the mobility of K+ was greater than that of the smaller Li+ cation, too. A high K+ transference number is beneficial for reducing concentration polarization within batteries. From a broader perspective, although high ion conductivity and transference number does not suffice to fully characterize an electrolyte and predict its behavior in a K ion cell, these properties are prerequisites.Transference number is another transport property, which quantifies the valid fraction of ion conductivity. The fraction of the current carried by cation is for ongoing electrochemical reactions, thus, high ionic transference number of cation t+ is bene2.2.2+‐solvation. The M+‐solvation effect is correlated with the ionic kinetics, SEI components, and the stability of batteries. The behaviors of active M+ on interfaces are always accompanied by the solvation/desolvation processes, which have great influence on the M+ migration. Figure +, Na+, K+ in common organic solvents. In contrast to Li+, which exhibited a well‐defined tetrahedral arrangement with EC molecules, the larger Na+ and K+ showed more disordered and flexible solvation structures. Specifically, Na+ and K+ exhibited increased average coordination numbers of 5.7 and 7.6 /highest occupied molecular orbital energy, respectively. When solvents or anions coordinate with cations, the coordinated cations attract electrons from solvent molecules and reduce the LUMO energy level of electrolytes. When the reductive decomposition potential of anode below the LUMO, some side reactions would occur at interfaces, for instance electrolyte reduction and gas evolution, as well as, formation of the passivation layer (SEI). This principle is applicable to many other divalent cation‐solvent systems, including Mg2+, Zn2+, and Ca2+ cations and ester and ether solvents  and time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS). Figure 2─COO─, ─OC( = O)O─, and ─C( = O)─ bonds in alkoxides and alkyl carbonates, which were the reduction products of the PC. Obviously, Li and K cell displayed higher C 1s peak intensities than that of Na cell, indicating thicker SEI in the Li/K cell with large amounts of organic/inorganic components. Carefully identify, the SEI in the K cell had a different amount of inorganic species derived from FSI− from that in the Li cell. The F 1s and S 1s spectra  and inorganic  were observed. Nevertheless, mainly inorganic  were observed in the TOF‐SIMS spectra, which indicated a comparatively high solubility of organic compounds in K/Na‐ion SEI. The above results revealed that the optimal formulation of electrolytes for K‐ion batteries should not be same with those used for Li and Na. Hess also reported the Li, Na, K metal anode SEI possessed increased ohmic resistor , high boiling point (Tb), high flash point (Tf), high stability, environmentally‐friendly, and low‐cost. Therefore, solvents of very different physical and chemical natures are often mixed to perform various functions simultaneously. The most commonly used solvents fall into three families: Carbonate ester, ether, and phosphate ester.The organic electrolytes are composed of three major components solvents, K salts, and additives. Solvent is the most important component of electrolyte. An ideal solvent should meet the diverse requirements, for example, high dielectric constants, low viscosity, low melting point , and trimethyl phosphate (TMP) , ethylene carbonate (EC), EMC, DEC, and DMC. Ether solvents have good compatibility with alkali metals, while the poor oxidation resistance limits their applications. The conventional ether solvents include DME, diethylene glycoldimethyl ether (DEGDME), triethylene glycol dimethyl ether (TEGDME), and 1,3‐dioxacyclopentane. With the effort to developing nonflammable electrolytes, organic phosphate as fire‐retardant solvents have been reported,57 sucP) Table . As shown in Figure 6 in EC/PC electrolyte showed high coulombic efficiency and long cycle life. The authors inferred that the worse performance was related with the poor stability of DEC and DMC at low voltage, which also confirmed by Ponrouch and Kang. Moreover, new battery electrodes would incur new electrolyte compositions. Guo et al. compared the electrochemical performance of red phosphorus (RP/C) alloy anode in EC/DEC and DME solvent, and demonstrated EC/DEC based electrolyte stabilized both K metal and RP electrodes for highly stable PIBs  calculations indicated that moderate solvation energy of KFSI based EC/DEC complex could facilitate K+ ion diffusion and desolvation on RP/C anode surface, and alleviate side reactions of electrolyte 2 (KFSI), KN(CF3SO2)2 (KTFSI), and KCF3SO3, and more research is focus on the applications of KPF6, and KFSI.An ideal salt for ambient rechargeable potassium batteries should meet the following minimal requirements, such as, high solubility, good electrochemical/chemical/thermal stability, low‐cost, and non‐toxic. Unfortunately, the kinds of K salts reported so far are rare. The common salts in K‐based batteries include KBF KCF3SO3,39 and4 and KClO4 salts, the poor solubility (0.05 M) in typical aprotic solvents lead to the low conductivity of the electrolyte, limiting their potential in potassium based batteries. In addition, KClO4 is rarely applied due to its strong oxidation. The high thermal stability and the passivation to Al foil make KPF6 based electrolyte be extensively studied. The major objective of KPF6 based electrolyte is adjusting functional solvents and additives, due to its moderate concentration (0.5–1.5 M). Lu et al. significantly improved the cycling stability of graphite anodes applied a high‐temperature precycling step to regulate the solvation structure of K+‐solvents in KPF6 based electrolyte.For KBFatteries.63 In 6 is extremely sensitive to oxygen and water, and easy to be decomposed HF, PF5, and POF3. Imides  as new‐type potassium salts, are considered as the most advantageous for negative electrodes. Specifically, Komaba et al. demonstrated the 3.9 M KFSI/DME realized the smallest polarization of 25 mV. KFSI/DME electrolyte could significantly improve the electrochemical performance of such kinds of electrodes, that is, carbonaceous material, alloy, and sulfide anodes by building highly stable SEI. However, low concentration KFSI based electrolytes exhibit Al corrosion at potential of ≈4.0 V versus K/K+. Therefore, there is a long way to design optimal electrolyte for potassium based batteries.However, KPFectrodes.65 Spe2.3.3 The typical roles of additives have already been confirmed in LIBs and SIBs. Therefore, additive is an important hotspot for high‐performance potassium based batteries.In general, additive is a kind of component with a mass fraction below 5%, but it is an indispensable part of the electrolytes in improving the target characteristics, including SEI forming agent, cathode protection agent, and safety protection agent, and so on.69 The alloy anode with large volume expansion , and high‐voltage cathode in LIBs and SIBs. Thus, the influence of FEC on cathode and anode in PIBs has also been studied. In 2017, the different effect of FEC on Prussian blue analogue (PBA) cathode in K half cells was investigated by Komaba et al. The 2 vol% FEC additive based electrolyte could improve the initial coulombic efficiency of K‐MnHCFe (from 61% to 90%), but the capacity retention was still low. Nazar et al. reported the similar conclusion that FEC enhanced the coulombic efficiency because it could not completely prevent electrolyte side reactions with successively consuming upon cycling. Moreover, FEC additives play a negative role in most anode electrodes. In K/Sn3P4 half cells, FEC accelerated the decomposition of the electrolyte, leading to greatly increased the polarization during cycling. Similar electrochemical behavior also exists in graphite and GeP5 anode.Currently, there are no specific potassium ion electrolyte additives. Fuoroethylene carbonate (FEC) can improve the stability of solvent under high voltage, and at the same time, FEC can effectively improve the interface stability of hard carbon,70 all For safer PIBs, Ming et al. first discovered that ethylene sulfate (DTD) was a promising additives, which made the electrolyte of 1.0 M KFSI in TMP more compatible with graphite anode. It was concluded that the DTD had a stronger coordination capability compared to that of TMP solvent. Thus, the DTD could replace one proportion of TMP solvent and participate in constructing the first solvation shell of central K+ ions, thereby determine the interfacial behaviors of K+‐solvent on electrode interface, and affecting the graphite performance. In addition to these solvent‐based additives, small amount of potassium difluorophosphate and blending salts have been developed recently.Apart from FEC, Komaba et al. systematically concluded the negative influence of well‐known additives on K metal plating, including fluoroethylenecarbonate (DFEC), vinylene carbonate (VC), and ethylenesulfite (ES).66 For33.1+‐based batteries do. In PIBs, generally, potassiated transition‐metal compounds work as cathodes, and carbonaceous materials, such as, hard carbon, graphite, as anodes for charge storage  /sulfur compounds as cathode paired with K metal anode. In 2015, the storage performance of graphite in carbonate ester (EC/DEC) electrolyte was demonstrated by Komaba et al. and Ji et al. Since then, various alloying, conversion anodes, and Prussian blue (PB), layered metal oxides, polyanionic compounds have been intensively investigated. In addition, there are numerous original works committed to designing advanced electrolytes and optimizing the electrode/electrolyte interface. These instructive works will discuss in the following sections. So far, KMBs  Figure  in 0.5 Ms Figure , potassis Figure  have eme3.2+ electrolytes for cathodes  and anodes Electrolytes in batteries must cater to the needs of electrodes, and new battery electrodes would incur new electrolyte compositions. At present, most researches focus on either single cathode or anode materials in PIBs with potassium as reference electrodes. Hence, Tables 3.2.1According to the electrochemical performance of cathodes and anodes reported, the PIBs still face several challenges. First, the initial columbic efficiency is too low to satisfy the requirement of PIBs full cell. Second, the unstable SEI would accelerate parasitic reactions, then, lead to short low capacity retention and cycle life. Finally, the type of electrolyte limited. Therefore, the development of electrolytes is urgently needed. Graphite is the most used anodes for PIBs, thus, we review recent findings on it to understand the development of electrolytes.+ electrochemical intercalation behaviors into commercial graphite in 0.8 M KPF6 based electrolytes.[81b] They proved potassium graphite intercalation compounds (K‐GIC) have the same structure with that of Li‐GIC  and corresponding the KC8 compounds , maintained 88.5% capacity retention after 100 cycles in PIBs  additive further made TMP based electrolyte more compatible with graphite anode. The graphite showed a high initial CE and rate capability in such a newly designed electrolyte with 6 wt% DTD  with high ionic conductivity and wide electrochemical window , K single cation IL  with high K+ transport number and good compatibility with graphite anode. Nevertheless, the understanding of interface between graphite and ILs is not as mature as the LIBs/SIBs, and the application of ILs in PIBs is in the initial stage. Despite some breakthroughs in electrolytes for graphite have been made, the electrolyte designing for various cathode materials and full batteries are scarce.Currently, novel fire‐retardant ionic liquids (ILs) have been developed for high performance PIBs. They exhibit excellent physical properties, such as K[FSI]‐[C3C1pyrr][FSI] (C3C1pyrr = ctively),121 K 3.2.2xMA[MB (CN)6]y·zH2O, where MA and MB are transition metals , A is alkali metal , and x ranges from 0 to 2 depending on the valance of MA and MB. The first research on the activity of KFe[Fe(CN)6] for K+ storage capacity was reported in 2004, and the reaction mechanism was proposed in 1 M KBF4 based EC/EMC electrolytes. However, the low specific capacity is difficult to meet demand. Therefore, K1.89Mn[Fe(CN)6]0.92·0.75H2O as a cathode for KIBs was proposed. This material showed experimental capacity of 142 mAh g−1 in KClO4 salt based electrolyte, close to the theoretical discharge capacity of 156 mAh g−1. However, it experienced a large voltage polarization (>0.5 V) due to low the ionic conductivity induced by low concentration of KClO4 salt. However, it showed high polarization during charging and discharging process. Later, Komaba et al. demonstrated higher discharge plateaus for the same compound in KPF6 based EC/DEC electrolytes. However, the higher voltage could reduce the stability of electrolyte and accelerate the solubility of transition metals. Therefore, the high voltage resistance and interface stability electrolyte is the future development direction, such as, local high concentration electrolytes (LHCEs), ionic liquid, molten salt electrolytes, and solid electrolytes.So far, PBAs have been widely used as cathodes for PIBs. They belong to metal hexacyanoferrates family with composition of A3.33.3.1 Considerable efforts have been made to solve these problems, such as, constructing various conductive hosts and artificial SEI, developing current‐controlled and modifying electrolytes. The morphological characteristics and structural stability of SEI film play an important role in the capacity, power, cycle life, and high temperature stability of battery. Wu et al. first reported high concentrated KFSI/DME electrolyte could enable reversible potassium plating/stripping  for safe and high‐capacity KMBs. It showed high ionic conductivity of 13.1 mS cm−1 at 22  (PMMA) GPE in K||polyaniline cell. The GPE with high conductivity of 4.3 × 10−3 S cm−1 realized reversible plating/stripping of K at room temperature  as the cell with the organic liquid electrolyte at 10 mA g−1 /potassium iodide (KI) GPE with conductivity of 2.089 × 100.358 eV.131 Gae Figure . Moreovee Figure . The K||1 Figure , and eve1 Figure . Recentl However, the customized electrolytes for K‐based batteries are far behind lithium and sodium metal. Thus, in this context, the research of electrolyte materials and science, especially the fundamental understanding of interfacial processes, constitutes the key areas for future K ions storage.In addition, several notable successes have achieved for stable K plating/stripping based on regulating the nucleation and deposition of K ions. For example, infiltrated carbon nanotube membranes, functionalized 3D copper, and puffed millet/NiO current collectors, Na‐K alloy and Sn‐based solid‐electrolyte interphase were developed to stabilize the metal front.134 Ho3.43.4.1−1, much higher than the current commercial lithium‐ion battery, which is a key motivation for further study. The high abundance and low cost of sulfur further make it a great potential for the next generation of rechargeable batteries. Alternatively, Se cathode with remarkable electrical conductivity of 1.0 × 10−3 S cm−1 and comparable theoretical volumetric capacity, is also a promising cathode material. Therefore, K‐S/Se batteries are considered as ideal choices for the next generation of high energy density battery system. However, the research of K‐S batteries system is still in the preliminary stage and faces a series of challenges including the electrochemistry of sulfur and sulfide/polysulfide, K metal anode, compatible electrolyte, as well as, the overall aspects of full‐cell.Like ‐sulfur batteries, potassium‐sulfur (K‐S) batteries has a theoretical energy density of 914 Wh kger study.135 Th[135a] The S cathode showed a sloping region and a platform at about 1.8 V in the ether based electrolyte /sulfur composites as the cathode in TEGDME based electrolyte Figure .[135a] Te Figure . Howevers Figure . To enabs Figure ., and found that ionic conductivity (σ) increased with the increasing of salt in the host polymer PEO. It displayed maximal σ (5.0 × 10−7) at 30 wt% of salt KBr  have emerged as promising materials for K‐based batteries due to its competitive advantages over liquid organic electrolytes and ISEs. On the one hand, compared with organic electrolytes, PEs with appropriate mechanical strength could effectively suppresses the growth of dendrites and accommodate volume changes of electrode materials. On the other hand, compared to ISEs, PEs emerged as advantageous materials for flexibility, easy film forming, excellent interface compatibility with electrodes.18 Ther Figure . Agrawal+ in potassium‐based batteries. Therefore, various polymer matrix materials with different K salts have been designed, such as, poly, PVDF‐HFP, poly with 18 wt % KFSI. Moreover, the CV and LSV profiles revealed K metal could reversibly plate/stripe in a wide electrochemical window   Figure  displaye) Figure .2− units, and it showed ion conductivity of 1.19 × 10− 3 S cm−1 at 800°C.NASICON  by high‐throughput computational method. For ISEs, the main shortages of K+‐based ISEs are poor interface instability and compatibility with electrodes. What is worse, the ISEs researches are still in its infancy, only a few K+ ionic conductors were developed . Finally, realizing large‐scale production of high‐performance K‐based batteries via developing low‐cost electrodes, and binders and separators.There are no conflicts to declare.


The clinical effect of postoperative radiotherapy (PORT) in non‐malignant meningioma (NMM) has not been well explored.n = 7716, postoperative radiotherapy group: n = 913) were obtained from the Surveillance, Epidemiology, and End Results database. Patient profiles were matched by 1:1 propensity score matching (PSM). Logistic regression analysis was performed to identify factors associated with PORT versus surgery alone (SA). Univariate and multivariate Cox regression analyses determined prognostic variables with overall survival (OS) in NMM. Subgroup analyses were performed with Cox proportional hazards regression models.A total of 8629 patients with NMM  and PORT (n = 913) groups were included. Women with PORT (66.3%) and SA (70.9%) were almost twice as likely as men, and tumors with benign behaviors in the SA group were almost seven times more frequent than those with malignant characteristics. We explored the demographic, clinical characteristics, and prognostic factors in NMM. Laterality, surgery, tumor size, diagnosis year, age, and tumor behavior were associated with PORT versus SA. Patients treated with PORT had better OS than those treated with SA (p = 0.03). After PSM, PORT remained comparable to SA . In the subgroup analysis of PORT treatment, borderline malignant behavior increased the death risk by 23%, while other variables did not have a significant clinical benefit (p > 0.05).All the SA (Borderline malignant behavior should be considered seriously, and the PORT regimen should be actively implemented for patients with benign meningiomas. Non‐malignant meningiomas (NMMs) are the most common histological type, accounting for more than half of the primary brain and central nervous systems.Postoperative radiotherapy (PORT) has been shown to improve the prognosis of WHO Grade III meningiomas, and conventional PORT has become the standard treatment.We performed a large population‐based study to determine the effect of PORT on NMMs using propensity score matching (PSM) to eliminate baseline differences between samples. We also compared the overall survival (OS) and the impact of clinical subgroup on survival. To the best of our knowledge, this study is the first to report treatment differences in PORT in a PSM‐matched patient population.22.1Patients included in the study were selected from all 17 registries (2000–2019) in the Online Access website, SEER database. We selected data from 2016 to 2019. The inclusion criteria included patients aged ≥20 years with histologically verified NMMs . The study design is shown in Figure 2.2In patients with histologically positive NMMs, data for the following variables were collected: sex , laterality , surgery , gross total resection (GTR), marital status , tumor size at diagnosis , race , age , diagnosis year , behavior code . Any other treatment and patients with incomplete surgical records were excluded from the surgical cohort. For the PORT cohort, data on preoperative radiotherapy, chemotherapy, and other treatments were excluded. Survival data included survival status  and survival month . The primary outcome was OS in patients with NMM receiving PORT.2.3U test, chi‐square analysis, and Fisher's exact test (where applicable). Univariate and multivariate logistic regression analyses were used to investigate the demographics associations and clinical characteristics for the relationship between PORT and SA in NMM. Prognostic characteristics were assessed for univariate Cox (p < 0.05) and multivariate Cox (p < 0.01) regression models. The Kaplan–Meier (KM) method was used to assess survival in the SA and PORT groups and clinically characterized subgroups. The risk was expressed as a hazard ratio (HR) with a 95% confidence interval (CI) to investigate the effect on survival outcomes between subgroups. All statistical analysis results in this study were generated in the R environment . A p‐value < 0.05 was considered statistically significant.All patients were grouped according to the treatment modality: SA and PORT. The patients' clinical characteristics were described as categorical variables (%), and distributions between the groups were compared using the Mann–Whitney 2.4To simulate a randomized trial, 1:1 PSM was used to reduce selection bias, and the R package “MatchIt, version:4.5.0” performed “nearest” matching of baseline data of patients in the SA and PORT groups,33.1n = 7716) and PORT groups (n = 913). The significant clinical differences between the two groups are shown in Table p < 0.05).This study included 8629 patients with NMM Table , divided3.2p < 0.001), surgery , tumor size , year of diagnosis , age , and behavior code  were most closely related to PORT.In univariate logistic regression analysis, sex, laterality, surgery, tumor size, year of diagnosis, age, and behavior code were related to PORT Table . In the p < 0.001). Borderline malignancy behavior was more common in males than that in females . Borderline malignancy behavior was lower in laterality  than that on the right side . Borderline malignancy behavior was less common in smaller tumors , and proportionately less common in White patients compared to that in Black patients . Age was also influential, with borderline malignancy behavior being proportionately less common at ages 40–59  and 60–79 .Next, we assessed whether the relationship between borderline malignancy behavior and PORT was affected by other variables. Furthermore, we examined the relationship between borderline malignancy behavior and other variables Table . There w3.3n = 7716) and PORT groups (n = 913) were 92.8% (95% CI 92.0%–93.6%) and 93.8% (95% CI 91.5%–96.1%) (p = 0.03), respectively . Univariate Cox regression analysis showed a 40% reduction in death risk in the PORT group compared to that in the SA group. Moreover, multivariate Cox regression indicated a similar death risk (44%) in the SA (n = 854) and PORT groups (n = 854) after PSM (Table p = 0.024), respectively  did not benefit from PORT treatment, whereas the OS for right‐sided tumors  did improve (Table p < 0.0001) , be aged between 40 and 59 years, and have tumors categorized as showing benign behavior. Patients in the PORT group showed better OS than those in the SA group.In an analysis of patients with NMM receiving PORT and SA treatment, tumors showing borderline malignancy and benign behavior were strongly associated with PORT treatment. As the incidence of tumors showing benign behavior is 7–8 times higher than that of borderline malignancy, this may partly explain the survival benefit observed in the PORT group. However, the incidence of tumors showing benign and borderline malignancy behavior treated with PORT was almost similar. Total surgical excision is the treatment of choice for the most prevalent benign meningiomas, as determined by a consensus. Radiotherapy is performed for recurrent or persistent tumor growth following surgical excision.Our results showed that a higher proportion of women who received PORT treatment than those who received SA. Meningiomas are significantly more common in women than those in men.p = 0.004). However, laterality, tumor size, race, and age did not appear to influence survival benefit in those receiving PORT (p > 0.05).After PSM, patient characteristics were eliminated to the greatest extent possible. The 3‐year survival rate of patients with NMM was similar between the SA and PORT groups (both before and after PSM). Furthermore, compared to the SA group, the PORT group had a greater reduction in death risk in univariate and multivariate Cox regression analyses. In the PORT subgroup analysis, multivariate Cox regression showed similar results to logistic regression, with borderline malignancy behavior comparable to benign behavior with a 23% increased death risk after PORT treatment  or tumor sizes (≥42 mm and <42 mm).Our research has several limitations. First, the SEER database does not include patient‐specific clinical information, including gene expression‐related data. Existing studies have confirmed that inactivation of the most common NF2 tumor suppressor gene5This was a large‐scale population‐based study that comprehensively delineated the differences in demographics, clinical characteristics, and prognosis between patients receiving PORT and surgical meningioma resection. PORT had a better prognostic benefit than SA, and after adjustment for other covariates by PSM, only tumors exhibiting benign behaviors were found to be benefited from PORT treatment. We recommend the aggressive implementation of PORT in patients with benign meningioma. More research is required to determine specific treatment options for PORT in NMM.Yongan Jiang: Data curation ; methodology ; writing – original draft . Peng Chen: Data curation ; methodology ; writing – review and editing . JiaWei Liang: Data curation ; methodology ; writing – review and editing . JiaHong Cai: Formal analysis . Yi Zhang: Formal analysis . HengYi Fan: Writing – original draft . RaoRao Yuan: Investigation ; validation . WenXing Zheng: Software ; validation . ShiQi Cheng: Conceptualization ; funding acquisition . Yan Zhang: Conceptualization ; funding acquisition ; project administration .JiangXi Provincial Health Commission Science and Technology Program (No. 202130385). JiangXi Provincial Education Bureau Program (No. GJJ210118). National Natural Science Foundation of China (No. 82260388). Jiangxi Administration of Traditional Chinese Medicine Program (No. 2022Z017).This research does not include any research conducted by any author on human participants or animals. The authors declare no competing interests.Figure S1:Click here for additional data file.Table S1:Click here for additional data file.Table S2:Click here for additional data file.Table S3:Click here for additional data file.


Accessibility to the immense collection of studies on noncommunicable diseases related to coronavirus disease of 2019 (COVID‐19) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an immediate focus of researchers. However, there is a scarcity of information about chronic obstructed pulmonary disease (COPD), which is associated with a high rate of infection in COVID‐19 patients. Moreover, by combining the effects of the SARS‐CoV‐2 on COPD patients, we may be able to overcome formidable obstacles factors, and diagnosis influencers.A retrospective study of 280 patients was conducted at DHQ Hospital Muzaffargarh in Punjab, Pakistan. Negative binomial regression describes the risk of fixed successive variables. The association is described by the Cox proportional hazard model and the model coefficient is determined through log‐likelihood observation. Patients with COPD had their survival and mortality plotted on Kaplan–Meier curves.The increased risk of death in COPD patients was due to the effects of variables such as cough, lower respiratory tract infection (LRTI), tuberculosis (TB), and body‐aches being 1.369, 0.693, 0.170, and 0.217 times higher at , (95% CI: 0.231–1.156), (95% CI: 0.008–0.332), and (95% CI: −0.07 to 0.440) while it decreased 0.396 in normal condition.We found that the symptoms of COPD  are statistically significant in patients who were most infected by SARS‐CoV‐2. This study reveals that cough; LRTI, TB/PTB, and body‐aches were the main causes of COPD in COVID‐19. Controlling these four factors reduces the chances of COPD patients contracting (COVID‐19 and SARS‐CoV‐2) and improves their chances of recovery. Clinical and scientific professionals focused on patients with chronic obstruct pulmonary disease (COPD), who may be more likely to get infected with coronavirus disease of 2019 (COVID‐19) than other people.The European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association are working on reliable COPD diagnostic guidelines.Over 79 million cases of COVID‐19 have been confirmed worldwide since the World Health Organization (WHO) declared the disease pandemic in 2020, with 6,444,316 deaths on December 5, 2022. During COVID‐19, all over the world, 0%–10% of patient were diagnosed with COPD. The prevalence of COPD in Sub‐Saharan Africa is between 4.1% and 24.8%, despite the region's high incidence of infectious diseases like HIV and tuberculosis that serve as major risk factors for COPD.The disease COPD affects not only a country's healthcare system but also the quality of life of patients and their families. In Pakistan, from January 3, 2020, to December 3, 2022, there were 1,575,486 confirmed cases of COVID‐19, with 30,635 deaths reported to the WHO,1.1To confront the escalating causes of these diseases, improved policymaking and intervention, it is necessary to examine the connections between the diseases and the factors that influence them. In the present analysis, 12 independent factors (diagnosis) such as body‐aches, wheezing, headache, normal condition, shortening of breath (SOB), tuberculosis (TB), lower respiratory tract infection (LRTI), Acid Fast bacillus (AFB), right‐side chest pain, sputum, cough, and fever were selected to examine the impact of risk factors for COPD and to explore the link between different risk factors.22.1In this study, secondary data from 280 male and female COPD patients with COVID‐19 were taken from a population of 4,348,5492.22.2.1In geometric experiments, it is only interesting if the first success occurs, and we repeat the experiment even if the first success does not occur. However, in many situations, this extended to a fixed number of successes rather than a single source.2.2.2p and k two‐parameter used in negative distribution.p = probability of success.k = number of success.Pmf:X = number of trials to produce k successes.q = 1 − p2.2.3ϑ” is the set of regression coefficient and “Ki” is the set of independent variables describing a person “ι” which may be either “dummy variables” or regular continuous variables.2.2.4h (t1) which can be interpreted as a risk with respect to time t1. It can be calculated as follows1.t1 represent the survival time.2.h(t1) functions determine the p covariate  with coefficient  which measure the covariates in Equation (as3.(H.R = 1): No‐effect occur, (H.R > 1); increase in hazard, (H.R < 1): Reduction in hazard,It is used to evaluate the simultaneous effects of different factors on survival. It identifies specific factors of influence or events happening . A Hazard‐function is denoted by h t1 which ch t1 which c2.2.5These are 12 hypotheses drawn from the diagnoses of COPD patients who have COVID‐19.H1 = Fever has a significant effect on COPD.H1 = Cough has a significant effect on COPD.H1 = Sputum has a significant effect on COPD.H1 = LRTI Infection has a significant effect on COPD.H1 = AFB has a significant effect on COPD.H1 = Normal condition has a significant effect on COPD.H1 = SOB has a significant effect on COPD.H1 = body‐aches has a significant effect on COPD.H1 = Headache has a significant effect on COPDH1 = Wheezing has a significant effect on COPD.H1 = Right side chest pain has a significant effect on COPD.H1 = TB/PTB has a significant effect on COPD.3p = .000), and 82.9% survived during hospital treatment, while 17.1% died (p = .000). In district Muzaffar‐garh tehsil, namely, Muzaffar‐garh, Kot‐Adu, Jatoi, and Ali‐Pur, the patient ratio was distinguished with respect to 53.9%, 12.5%, 22.9%, and 10.7% of those treated with COPD that also have COVID‐19 disease. During the treatment, the patient had symptoms like fever, cough, sputum, LRTI, AFB, TB/PTB, normal condition, SOB, body‐aches, headache, wheezing, and right side chest pain with 54.6%, 87.1%, 42.5%, 9.3%, 36.4%, 43.6%, 17.1%, 92.1%, 65%, 96.4%, 9.3%, and 63.9%.In the descriptive analysis Table , patient3.1p = .051), and it demonstrates a strong association among independent variables. The graph's result pattern is depicted by Kaplan–Meier curves based on gender and area: (a) Time to Hazard gender‐wise graph (b) time to survival gender‐wise graph (c) area‐wise graph of time to hazards (d) area‐wise graph of time to survival. In , (95% CI: 0.231–1.156), (95% CI: 0.008–0.332), and (95% CI: −0.07 to 0.440) while it decreased 0.396 in normal condition. Patients diagnosed with COPD had a higher mortality rate and showed less improvement over time. Furthermore, our findings demonstrated that COVID‐19 case fatality rates were higher in regions with a higher prevalence of COPD. Similarly, the number of cases of COVID‐19 is increasing exponentially in many developing countries where rates of COPD are rising and there is a notable disparity between illnesses.A larger sample size is desirable, but multiple factors affect study conclusions. Our 280‐patient study draws meaningful and useful conclusions by ensuring sample representativeness, using appropriate statistical techniques, considering effect size and precision, relating findings to existing evidence, and acknowledging limitations. From a total of 280 patients, 76.8% were males and 23.2% were females; we divided them into groups at suitable intervals between the ages of 14 and 84. The Cox proportional hazard model revealed a strong association between the variables, and the negative binomial distribution indicates that the model was significant, as well as the patients' relative risk. Results confirmed that the survival rate decreased when the patient was in a critical situation. The treatment was highly effective for COPD patients who had cough, LRTI, TB/PTB, and bodyaches. Several studies have examined at the correlation between SARS‐CoV‐2 and COVID‐19 status; individuals with COPD are more likely to worsen if they test positive. In the related cohort study, symptoms such as confusion, anxiety, weariness, exertional dyspnea, sleeplessness, sadness, cough, and bowel problems were the most prevalent with  symptoms at 12‐month contact.Our research shows that COPD patients' risk of dying from any cause is affected more by their diagnosis than by demographic variables like age, gender, or location. However, owing to a lack of patients with severe COPD, we were unable to accurately assess the effect of severity, therefore, these findings should be interpreted with caution. Despite our best efforts, we may have overlooked mild instances of COPD when no medicine was used for maintenance. Having individuals with COPD and no other diseases would have made it simpler to rule out other causes, but we missed this information in our research, so our estimations could be inaccurate. We excluded persons whose dates were missing from the survival analysis. To examine the dispersion of potential confounding variables in the samples used for each time‐to‐event study, statistical tests were performed. It made sure that COPD patients weren't drastically different from one another. The key outcomes of death and recovery may be lacking some data. This was remedied by excluding patients who did not reach a final result on the last day of follow‐up from the survival analysis (LAMA cases).This may have affected the comparison between those with severe and those with mild COPD.Furthermore, COVID‐19 and COPD are linked directly, while SARS‐CoV‐2 indirectly leads to COPD morbidity and death. Health systems worldwide were affected by COVID‐19, and it is predicted that medicine shortages and delays in the identification and treatment of COPD will increase death rates for persons with the disease.Our results highlight the need of maintaining high standards for COPD screening and monitoring programs. To defeat the epidemic, strategic health planning and resource allocation were required. More extensive follow‐up research with large enough samples to draw meaningful conclusions is needed. This research contains enough patients, in light of what we found, to examine the relationship between COPD and a high‐burden lifestyle.5After scrutinizing 12 independent variables (diagnosis), this study reveals that cough; LRTI, TB/PTB, and bodyaches were the main causes of COPD in COVID‐19. Controlling these four factors reduces the chances of COPD patients contracting (COVID‐19 and SARS‐CoV‐2) and improves their chances of recovery. Our research has important implications for the organization of health care for COVID‐19 patients and for prioritizing health interventions and protection measures toward the most vulnerable chronic patients. Disease combinations should be evaluated for successful infection prevention in severe instances of infection.Muhammad Muneeb Hassan: Conceptualization; data curation; formal analysis; investigation; software; validation; visualization; writing—original draft; writing—review & editing. M H Tahir: Formal analysis; investigation; project administration; supervision; validation; visualization; writing—review & editing. Muhammad Ameeq: Conceptualization; data curation; formal analysis; investigation; methodology; resources; software; validation; visualization; writing—original draft; writing—review & editing. Farrukh Jamal: Formal analysis; investigation; methodology; project administration; supervision; visualization; writing—review & editing. John T Mendy: Formal analysis; project administration; supervision; validation; visualization; writing—original draft; writing—review & editing. Christophe Chesneau: Investigation; writing—original draft; writing—review & editing.The authors declare no conflict of interest.The review board statement of this study is available from the corresponding author upon reasonable request.Not applicable, because secondary data of discharged patients were collected from the hospital record with the approval of the ethical committee.