• IMA sites
  • IMAJ services
  • IMA journals
  • Follow us
  • Alternate Text Alternate Text
עמוד בית
Tue, 22.07.25

Search results


July 2025
Lia Mazur, Avishai M. Tsur MD MHA, Harald Heidecke PhD, Kai Schulze-Forster PhD, Abdulla Watad MD, Howard Amital MD MHA, Yehuda Shoenfeld MD FRCP MaACR, Gilad Halpert PhD

Background: Silicone breast implants (SBIs) are associated with subjective and autoimmune related manifestations, ranging from reported symptoms such as depression and fatigue to diseases such as Sjögren's syndrome and systemic sclerosis.

Objectives: To examine whether autoantibodies directed against autonomic nervous system receptors are associated with reported symptoms of dry mouth and eyes in patients with SBIs.

Methods: ELISA assays were used to evaluate a panel of 11 autoantibodies in the sera of patients with SBIs and age-matched healthy controls.

Results: Four autoantibodies (anti-angiotensin II type 1 receptor, anti-β1 adrenergic receptor, anti-muscarinic receptors M2, and anti-muscarinic receptors MR) had significantly lower median titers in SBI recipients who reported dry mouth compared to the control group (9.9 vs. 15.7, P < 0.001; 8.8 vs. 23.3, P < 0.001; 3.2 vs. 4.7, P < 0.001; and 6 vs. 8.8, P = 0.0011, respectively). Anti-muscarinic receptor M4 had significantly lower median titers in patients with SBIs who reported dry eyes compared to the control group (5.9 vs. 8.8, P = 0.0039).

Conclusions: A dysregulation of the autonomic nervous system in SBI recipients was correlated with the presence of dry mouth and dry eyes. Our results emphasize the need to further investigate the proposed involvement of the autonomic nervous system in subjective symptoms reported by SBI recipients.

Mor Amital MD, Yehuda Shoenfeld MD FRCP MaACR, Arkadi Yakirevitch MD

Chronic cough is a common clinical symptom with a broad differential diagnosis, including respiratory, gastrointestinal, and neurological causes. A rare yet important cause is Arnold’s nerve reflex (ear-cough reflex) and triggered by stimulation of the auricular branch of the vagus nerve. We present the case of a 77-year-old man with a persistent dry cough and no significant medical history other than mild hypertension. The patient reported paresthesia in his left ear and noted that his cough was often triggered by touching the ear. A comprehensive physical and neurological examination, including otoscopy, was performed. Examination revealed cerumen impaction covering the posterior wall of the left external ear canal. Removal of the cerumen immediately triggered a cough but resulted in complete resolution of symptoms within one day. This case emphasizes the importance of considering Arnold’s nerve reflex as an underlying cause of chronic cough. A thorough physical examination, particularly otoscopy, is essential for accurate diagnosis. Understanding the neuropathic basis of the ear-cough reflex provides insights into targeted management including neuromodulator therapy.

June 2025
Meital Oren-Shabtai MD, Assi Levi MD, Daniel Mimouni MD, Hadas Prag-Naveh MD, Elena Didkovsky MD, Elisheva Pokroy-Shapira MD, Emmilia Hodak MD, Iris Amitay-Laish MD

Background: Mycosis fungoides (MF) combined with photosensitive/autoimmune diseases has been reported, yet there are limited data regarding the therapeutic considerations in these patients, specifically phototherapy, a mainstay skin-directed treatment (SDT), being a relative or complete contra-indication.

Objectives: To outline therapeutic considerations for patients with MF who had also been diagnosed with photosensitive/autoimmune diseases.

Methods: We conducted a retrospective analysis of patients with MF who were treated at our center between January 2008 and December 2024with photosensitive/autoimmune diseases, especially collagen vascular diseases (CVD) or autoimmune bullous diseases (AIBD),

Results: Eight patients were diagnosed with MF at a median age of 39 years. Seven had early-stage (4-IA, 3-IB) and one had Sézary syndrome. Six early-stage MF patients were diagnosed with lupus erythematosus (LE, 4) or AIBD (2) and were treated with SDT (topical corticosteroids/chlormethine gel), systemic retinoid or methotrexate. A patient with resistant early-stage MF and discoid LE was treated with electron beam and interferon. One patient who presented with variegate porphyria and localized MF was treated with electron beam. The patient with Sézary syndrome had inclusion body myositis. He was treated with low-dose total skin electron beam, methotrexate, extracorporeal photopheresis, and subsequently with romidepsin. After a median of 8 years, no stage progression of MF was observed. The Sézary syndrome patient achieved down-staging and was at stage IB. There was no aggravation of the co-morbidity in any of the patients.

Conclusions: Effective management of MF and associated photosensitive or autoimmune co-morbidities underscore the need for individualized treatment strategies in patients with these unique dual diagnoses.

Ayelet Ollech MD, Yizhak Confino MD, Rivka Friedland MD, Dan Ben Amitai MD, Vered Molho-Pessach MD, Michal Neumark MD, Jacob Mashiah MD, Liat Samuelov MD, Ayelet Shani-Adir MD, Hiba Zaaroura MD, Eran Cohen-Barak MD, Amir Horev MD, Yulia Valdman MD, Baruch Kaplan MD, Shoshana Greenberger MD

Infantile hemangioma (IH) is the most common benign vascular tumor in infancy. Recent advances, particularly in beta-blocker therapy, have significantly improved the management of IHs. Early identification and treatment of IH may help reduce morbidity and associated complications. In this review, experts in pediatric dermatology in Israel who have experience in treating IH formulated national guidelines for the diagnosis and treatment of IHs, providing evidence-based recommendations for selecting appropriate therapeutic approaches. These Israeli national guidelines provide a structured approach to the diagnosis and treatment of IH, emphasizing early referral, appropriate treatment selection, and careful monitoring. The guidelines serve as a critical resource for pediatricians and dermatologists, ensuring optimal patient outcomes while minimizing complications.

April 2025
Einat Savin MD, Kassem Sharif MD, Sharon Amit MD, Shomron Ben Horin MD

Crohn's disease patients undergoing anti-tumor necrosis factor (anti-TNF) therapy such as infliximab face potential risks from opportunistic infections. We introduce the unique case of a 66-year-old male Crohn's patient, previously in remission, presenting with gastrointestinal symptoms following a trip to the Czechia. Despite concerns of reactivated tuberculosis due to infliximab, his biopsies showed the presence of Mycobacterium simiae (M. simiae). Despite this, anti-TNF therapy was continued and resulted in clinical improvement. This is a case report of M. simiae in intestinal biopsies of an immunocompromised Crohn's patient is a clinical challenge. The findings suggest the benign colonization of M. simiae potentially influences future treatment considerations in similar clinical scenarios.

February 2025
Howard Amital MD MHA, Avishay Elis MD

It is indisputable that internal medicine is the cornerstone of medical activities, including medical education, in hospital clinical activities, and clinical and basic medical research.

The medical landscape in Israel is exceptionally demanding, far exceeding the norms of the countries that are members of the Organisation for Economic Co-operation and Development (OECD). We have fewer hospital beds per capita, a greater workload for each physician, and in the future, we will face the challenge of teaching more medical students across our current clinical fields.

The Israeli Society of Internal Medicine has made it its mission to advance internal medicine across all dimensions of the healthcare system in Israel. As such, for the third consecutive year, we are honored to present an issue of the Israel Medical Association Journal (IMAJ) dedicated to research in the different fields of internal medicine that are conducted by physicians from various departments across the country.

This year, we emphasize even more strongly that research is an integral part of our clinical practice. At a time when the basic sciences phase of residency is under threat, it is crucial to underscore its importance. In this issue of IMAJ, we have chosen to publish various studies that were conducted during the basic sciences phase of the residency in internal medicine, highlighting how this training period can be optimally utilized to advance research while simultaneously progressing and maturing through clinical training.

Yuval Kuntzman MD, Gilad Halpert PhD, Howard Amital MD MHA

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease pathway is heavily influenced by different inflammatory cytokines. There is ample evidence of cannabidiol (CBD) immunomodulation effects.

Objectives: To investigate the effect of CBD on patients with SARS-CoV-2 and to measure the impact on inflammatory cytokines.

Methods: A double blind, placebo-controlled study to compare the clinical outcomes and selected serum cytokine levels in patients with SARS-CoV-2 that received sublingual CBD extraction. Seven patients were randomized to the treatment arm and three to the placebo group.

Results: Clinical outcomes were better in the patient group that received sublingual CBD vs. patients receiving placebo treatment. Serum cytokine mean concentration levels showed differences between the two groups but of mixed trends.

Conclusions: Patients presenting with SARS-CoV-2 and receiving CBD sublingually had better outcomes than those receiving a placebo, although these results did not reflect in selected serum cytokines. Further study is needed.

Batsheva Varda MD, Arielle D. Zur, Yuval Kuntzman MD, Yonatan Shneor Patt MD, Howard Amital MD MHA, Arnon D. Cohen MD MPH PHD, Omer Gendelman MD

Background: Giant cell arteritis (GCA) is a large vessel vasculitis predominantly affecting patients over 50 years, typically managed with glucocorticoids, with treatment varying on individual patient needs. While effective for GCA, long-term glucocorticoids use poses significant risks, including the development of osteoporosis, a metabolic bone disease common in older individuals. This overlap poses a significant clinical challenge, as the treatment for GCA inadvertently raises the risk of osteoporosis and necessitates careful balance to manage both conditions effectively.

Objectives: To investigate the occurrence of osteoporosis and other co-morbid conditions in patients with GCA treated with glucocorticoids.

Methods: A retrospective cross-sectional analysis of GCA patients examined the correlation between GCA and osteoporosis by searching the Clalit Health Service database for patients over 50 years of age from January 2002 to January 2018. In addition, we conducted a logistic regression analysis stratifying for other co-morbidities to evaluate the independent association between GCA and osteoporosis.

Results: In total, 6607 GCA patients were compared with 36,066 age- and sex-matched controls. The study revealed a higher prevalence of osteoporosis in the GCA group (43%) compared to controls (27%) (odds ratio [OR] 2.06, 95% confidence interval [95%CI] 1.95–2.17). In addition, hypertension, hyperlipidemia, diabetes mellitus, and ischemic heart disease were more prevalent among GCA patients. After stratifying for cardiovascular co-morbidities, GCA remained independently associated with osteoporosis (OR 2.1, 95%CI 1.96–2.26, P < 0.001).

Conclusions: Glucocorticoid-treated GCA is independently associated with osteoporosis. Healthcare providers must consider this added aspect of GCA for the treatment and management of patients.

January 2025
Hagar Olshaker MD, Dana Brin MD, Larisa Gorenstein MD, Vera Sorin MD, Eyal Klang MD, Nisim Rahman BA, Michal Marianne Amitai MD

Background: On 7 October 2023, an armed conflict erupted between Hamas and Israel, leading to numerous combat casualties.

Objectives: To describe computed tomography (CT) findings of combat casualties at a tertiary medical center during the first 3 months of the conflict.

Methods: A retrospective observational study was conducted on patients admitted between 7 October 2023 and 7 January 2024. Adults with conflict-related trauma who underwent chest, abdomen, and pelvis (body) trauma protocol CT scans were included.

Results: Of 272 patients who underwent body trauma protocol CT, 112 combat-related adults were included, mean age of 27 years and one female. In total, 82 patients (73%) underwent additional scans of the head and neck or extremities. Fractures were observed in 53 patients (47%). Vascular injuries were present in 40 patients (35%). Limb injuries were most common, affecting 37 patients (33%), which prompted a protocol update. Lung injuries were the most common in body CT: 30 patients (27%). Head and neck injuries were seen in 21 patients (18%). Multisystem trauma was present in 24 patients (21%). A total of 83 patients (74%) underwent surgery, mostly orthopedic/soft tissue surgeries (63%); 15 (13%) underwent abdominal surgery, with bowel injuries confirmed in eight cases.

Conclusions: CT scans are an important tool in conflict trauma management. Limb injuries were the most frequent, necessitating protocol adjustments. Lung injuries were the most common body injury; 21% of patients had multisystem trauma. Most patients required surgery.

December 2024
Amit Oppenheim MD, Nabil Abu-Amer MD, Itai Gueta MD, Ramy Haj MD, Pazit Beckerman MD, David J. Ozeri MD

Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on patient populations can be divided to direct consequences of the disease and indirect implications of changes imposed on the national healthcare systems. The impact of the later survival of chronic hemodialysis patients is still unknown.

Objectives: To examine the impact of quarantine on health outcomes of dialysis patients.

Methods: In a retrospective case-controlled study, we compared chronic hemodialysis patients from two separate timeframes: during a quarantine period and a parallel time without quarantine.

Results: The study included 344 hemodialysis patients. Baseline characteristics were compared between those enrolled in 2015 and those enrolled in 2020. Despite comparable clinical parameters, a statistically significant increase in the 6-month mortality rate was observed in 2020 (1.2% vs. 6.7%, P = 0.01), primarily attributed to sepsis. Notably, no deaths were attributed to COVID-19 in 2020. Interdialytic weight gain and dialysis quality remained similar between the two groups, with a mild trend toward excessive weight gain in 2020. Secondary outcomes after 6 months did not significantly differ, except for lower sodium values in 2015 compared to 2020.

Conclusions: Dialysis patients experienced disproportionate effects from the COVID-19 pandemic, even with continuous care and no direct virus-related fatalities. The findings showed unintended consequences of quarantine measures, highlighting adverse impact on both physical and mental health. Recognizing and addressing these consequences are imperative for minimizing their impact in future pandemics, emphasizing the importance of proactive measures in healthcare planning.

November 2024
Noa Fried-Regev MD, Tzachi Slutsky MD, Amit Frenkel MD, Moti Klein MD, Shlomi Codish MD, Dan Schwarzfuchs MD

On 7 October 2023, the Hamas terror organization launched an unprecedented terror attack on Israel. Their forces infiltrated the country from the Gaza Strip invading nearby kibbutzim (collective farm settlements) and towns. During the attack an estimated 1200 Israelis were murdered and another 255 taken hostage, including children and older people, women and men.

September 2024
Mohamad Arow MD, Yonatan Shneor Patt MD, Zehavit Kirshenboim MD, Roy Mashiach MD, Howard Amital MD MHA

In this case report, we elucidated the complex etiology of new-onset ascites through the unusual presentation of a 32-year-old female with abdominal swelling, oliguria, and acute renal failure. This patient's ascites was attributed to urinary bladder rupture, a rare but critical consideration in differential diagnoses. Highlighting the significance of this case, bladder rupture without recent trauma history, especially post-gynecological surgery, poses a diagnostic challenge due to its rarity and potential for severe morbidity and mortality if not promptly recognized and managed. Our patient's journey, from initial symptoms to the eventual discovery of bladder rupture, underscores the necessity of considering this diagnosis in similar clinical scenarios. The case uniquely demonstrates pseudo-renal failure, a phenomenon resulting from reversed dialysis across the peritoneal membrane, which further complicated the diagnostic process.

Yair Binyamin MD, Amit Frenkel MD, Alexander Geftler MD, Israel Melamed MD, Salim Alobra MD, Alexander Zlotnik MD, Gali Pariente MD

The use of smaller-diameter, pencil-point spinal needles has increased to reduce post-dural puncture headaches in obstetric patients. However, this therapy has also led to more needle deformation and breakage. While risk factors and prevention are described, there is limited literature on management when breakage occurs.

The utilization of neuraxial techniques for labor analgesia and cesarean delivery has experienced a consistent increase in recent years [1]. Spinal anesthesia has emerged as the preferred technique for cesarean deliveries due to its advantages, including a reduction in morbidity and mortality, decreased complications related to airway management, reduced bleeding, improved bonding with the baby, and better outcomes for newborns [2]. While the adoption of smaller diameter, non-cutting bevel spinal needles has successfully reduced the incidence of post-dural puncture headaches in obstetric patients, it has also given rise to complications such as spinal needle deformation and breakage [3,4]. The current understanding of the incidence of neuraxial needle breakage remains limited, with estimated incidences reported between approximately 1 in 5,000 to 1 in 11,000 spinal anesthesia procedures performed [4]. Although numerous case reports have documented broken needles during attempted neuraxial anesthesia, the existing literature predominantly focuses on associated risk factors and preventive measures for this complication [3]. However, there is a lack of literature regarding the subsequent management once this adverse event has transpired. In this report, we present a case involving a broken spinal needle during an attempt to perform spinal anesthesia for an urgent cesarean delivery. By sharing this case, we shed light on the management strategies and considerations following such an event.

July 2024
Nadav Cohen MD, Andrii Li MD, Rooya Nejem MD, Ofer Lavie MD, Ariel Zilberlicht MD, Amit Reuveni MD, Zeev Goldik MD, Reuven Keidar MD, Vered Dvir MD

Background: Cesarean deliveries (CD) are commonly performed using neuraxial anesthesia. The use of neuraxial morphine has proven beneficial in terms of postoperative pain management; however, its effect on postoperative urine retention remains unclear.

Objectives: To determine whether morphine injection into the neuraxis during CD influences postoperative urinary retention rate.

Methods: We conducted a retrospective case-control observational study of patients undergoing CD. We compared patients using morphine injected into the intrathecal or epidural spaces (November 2020 to October 2021) to a historical cohort of patients undergoing CD without morphine (November 2019 to October 2020). The primary outcome was the rate of postoperative overt urinary retention necessitating bladder catheterization.

Results: The study group comprised 283 patients, and 313 patients in the control group were eligible for analysis. No differences were found with respect to the baseline demographic and indication for CD. The number of postpartum urinary bladder catheterizations due to urine retention was higher in the study group (5% vs. 1%, P-value = 0.003). No cases of 30-day readmission were recorded. Moreover, patients treated with neuraxial morphine required fewer repeat doses of postoperative anesthesia (oral analgesia 7.4 vs. 10.1, intravenous analgesia 0.29 vs. 0.31, oral opioids 0.06 vs. 3.70, intravenous opioids 0.01 vs. 0.45, P-value < 0.001 for all)

Conclusions: While neuraxial morphine used during CD appears to be safe and effective, the risk of postoperative urinary retention seems to be increased due to its use. Cases of overt urinary retention treated by bladder catheterization does not lead to short-term complications.

April 2024
Kassem Sharif MD, Adi Lahat MD, Yonatan Shneor Patt MD, Niv Ben-Shabat MD, Mahmud Omar MD, Abdulla Watad MD, Howard Amital MD MHA, Omer Gendelman MD

Background: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link.

Objectives: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship.

Methods: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors.

Results: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls.

Conclusions: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

Legal Disclaimer: The information contained in this website is provided for informational purposes only, and should not be construed as legal or medical advice on any matter.
The IMA is not responsible for and expressly disclaims liability for damages of any kind arising from the use of or reliance on information contained within the site.
© All rights to information on this site are reserved and are the property of the Israeli Medical Association. Privacy policy

2 Twin Towers, 35 Jabotinsky, POB 4292, Ramat Gan 5251108 Israel
ניתן להשתמש בחצי המקלדת בכדי לנווט בין כפתורי הרכיב
",e=e.removeChild(e.firstChild)):"string"==typeof o.is?e=l.createElement(a,{is:o.is}):(e=l.createElement(a),"select"===a&&(l=e,o.multiple?l.multiple=!0:o.size&&(l.size=o.size))):e=l.createElementNS(e,a),e[Ni]=t,e[Pi]=o,Pl(e,t,!1,!1),t.stateNode=e,l=Ae(a,o),a){case"iframe":case"object":case"embed":Te("load",e),u=o;break;case"video":case"audio":for(u=0;u<$a.length;u++)Te($a[u],e);u=o;break;case"source":Te("error",e),u=o;break;case"img":case"image":case"link":Te("error",e),Te("load",e),u=o;break;case"form":Te("reset",e),Te("submit",e),u=o;break;case"details":Te("toggle",e),u=o;break;case"input":A(e,o),u=M(e,o),Te("invalid",e),Ie(n,"onChange");break;case"option":u=B(e,o);break;case"select":e._wrapperState={wasMultiple:!!o.multiple},u=Uo({},o,{value:void 0}),Te("invalid",e),Ie(n,"onChange");break;case"textarea":V(e,o),u=H(e,o),Te("invalid",e),Ie(n,"onChange");break;default:u=o}Me(a,u);var s=u;for(i in s)if(s.hasOwnProperty(i)){var c=s[i];"style"===i?ze(e,c):"dangerouslySetInnerHTML"===i?(c=c?c.__html:void 0,null!=c&&Aa(e,c)):"children"===i?"string"==typeof c?("textarea"!==a||""!==c)&&X(e,c):"number"==typeof c&&X(e,""+c):"suppressContentEditableWarning"!==i&&"suppressHydrationWarning"!==i&&"autoFocus"!==i&&(ea.hasOwnProperty(i)?null!=c&&Ie(n,i):null!=c&&x(e,i,c,l))}switch(a){case"input":L(e),j(e,o,!1);break;case"textarea":L(e),$(e);break;case"option":null!=o.value&&e.setAttribute("value",""+P(o.value));break;case"select":e.multiple=!!o.multiple,n=o.value,null!=n?q(e,!!o.multiple,n,!1):null!=o.defaultValue&&q(e,!!o.multiple,o.defaultValue,!0);break;default:"function"==typeof u.onClick&&(e.onclick=Fe)}Ve(a,o)&&(t.effectTag|=4)}null!==t.ref&&(t.effectTag|=128)}return null;case 6:if(e&&null!=t.stateNode)Ll(e,t,e.memoizedProps,o);else{if("string"!=typeof o&&null===t.stateNode)throw Error(r(166));n=yn(yu.current),yn(bu.current),Jn(t)?(n=t.stateNode,o=t.memoizedProps,n[Ni]=t,n.nodeValue!==o&&(t.effectTag|=4)):(n=(9===n.nodeType?n:n.ownerDocument).createTextNode(o),n[Ni]=t,t.stateNode=n)}return null;case 13:return zt(vu),o=t.memoizedState,0!==(64&t.effectTag)?(t.expirationTime=n,t):(n=null!==o,o=!1,null===e?void 0!==t.memoizedProps.fallback&&Jn(t):(a=e.memoizedState,o=null!==a,n||null===a||(a=e.child.sibling,null!==a&&(i=t.firstEffect,null!==i?(t.firstEffect=a,a.nextEffect=i):(t.firstEffect=t.lastEffect=a,a.nextEffect=null),a.effectTag=8))),n&&!o&&0!==(2&t.mode)&&(null===e&&!0!==t.memoizedProps.unstable_avoidThisFallback||0!==(1&vu.current)?rs===Qu&&(rs=Yu):(rs!==Qu&&rs!==Yu||(rs=Gu),0!==us&&null!==es&&(To(es,ns),Co(es,us)))),(n||o)&&(t.effectTag|=4),null);case 4:return wn(),Ol(t),null;case 10:return Zt(t),null;case 17:return It(t.type)&&Ft(),null;case 19:if(zt(vu),o=t.memoizedState,null===o)return null;if(a=0!==(64&t.effectTag),i=o.rendering,null===i){if(a)mr(o,!1);else if(rs!==Qu||null!==e&&0!==(64&e.effectTag))for(i=t.child;null!==i;){if(e=_n(i),null!==e){for(t.effectTag|=64,mr(o,!1),a=e.updateQueue,null!==a&&(t.updateQueue=a,t.effectTag|=4),null===o.lastEffect&&(t.firstEffect=null),t.lastEffect=o.lastEffect,o=t.child;null!==o;)a=o,i=n,a.effectTag&=2,a.nextEffect=null,a.firstEffect=null,a.lastEffect=null,e=a.alternate,null===e?(a.childExpirationTime=0,a.expirationTime=i,a.child=null,a.memoizedProps=null,a.memoizedState=null,a.updateQueue=null,a.dependencies=null):(a.childExpirationTime=e.childExpirationTime,a.expirationTime=e.expirationTime,a.child=e.child,a.memoizedProps=e.memoizedProps,a.memoizedState=e.memoizedState,a.updateQueue=e.updateQueue,i=e.dependencies,a.dependencies=null===i?null:{expirationTime:i.expirationTime,firstContext:i.firstContext,responders:i.responders}),o=o.sibling;return Mt(vu,1&vu.current|2),t.child}i=i.sibling}}else{if(!a)if(e=_n(i),null!==e){if(t.effectTag|=64,a=!0,n=e.updateQueue,null!==n&&(t.updateQueue=n,t.effectTag|=4),mr(o,!0),null===o.tail&&"hidden"===o.tailMode&&!i.alternate)return t=t.lastEffect=o.lastEffect,null!==t&&(t.nextEffect=null),null}else 2*ru()-o.renderingStartTime>o.tailExpiration&&1t)&&vs.set(e,t)))}}function Ur(e,t){e.expirationTimee?n:e,2>=e&&t!==e?0:e}function qr(e){if(0!==e.lastExpiredTime)e.callbackExpirationTime=1073741823,e.callbackPriority=99,e.callbackNode=$t(Vr.bind(null,e));else{var t=Br(e),n=e.callbackNode;if(0===t)null!==n&&(e.callbackNode=null,e.callbackExpirationTime=0,e.callbackPriority=90);else{var r=Fr();if(1073741823===t?r=99:1===t||2===t?r=95:(r=10*(1073741821-t)-10*(1073741821-r),r=0>=r?99:250>=r?98:5250>=r?97:95),null!==n){var o=e.callbackPriority;if(e.callbackExpirationTime===t&&o>=r)return;n!==Yl&&Bl(n)}e.callbackExpirationTime=t,e.callbackPriority=r,t=1073741823===t?$t(Vr.bind(null,e)):Wt(r,Hr.bind(null,e),{timeout:10*(1073741821-t)-ru()}),e.callbackNode=t}}}function Hr(e,t){if(ks=0,t)return t=Fr(),No(e,t),qr(e),null;var n=Br(e);if(0!==n){if(t=e.callbackNode,(Ju&(Wu|$u))!==Hu)throw Error(r(327));if(lo(),e===es&&n===ns||Kr(e,n),null!==ts){var o=Ju;Ju|=Wu;for(var a=Yr();;)try{eo();break}catch(t){Xr(e,t)}if(Gt(),Ju=o,Bu.current=a,rs===Ku)throw t=os,Kr(e,n),To(e,n),qr(e),t;if(null===ts)switch(a=e.finishedWork=e.current.alternate,e.finishedExpirationTime=n,o=rs,es=null,o){case Qu:case Ku:throw Error(r(345));case Xu:No(e,2=n){e.lastPingedTime=n,Kr(e,n);break}}if(i=Br(e),0!==i&&i!==n)break;if(0!==o&&o!==n){e.lastPingedTime=o;break}e.timeoutHandle=Si(oo.bind(null,e),a);break}oo(e);break;case Gu:if(To(e,n),o=e.lastSuspendedTime,n===o&&(e.nextKnownPendingLevel=ro(a)),ss&&(a=e.lastPingedTime,0===a||a>=n)){e.lastPingedTime=n,Kr(e,n);break}if(a=Br(e),0!==a&&a!==n)break;if(0!==o&&o!==n){e.lastPingedTime=o;break}if(1073741823!==is?o=10*(1073741821-is)-ru():1073741823===as?o=0:(o=10*(1073741821-as)-5e3,a=ru(),n=10*(1073741821-n)-a,o=a-o,0>o&&(o=0),o=(120>o?120:480>o?480:1080>o?1080:1920>o?1920:3e3>o?3e3:4320>o?4320:1960*Uu(o/1960))-o,n=o?o=0:(a=0|l.busyDelayMs,i=ru()-(10*(1073741821-i)-(0|l.timeoutMs||5e3)),o=i<=a?0:a+o-i),10 component higher in the tree to provide a loading indicator or placeholder to display."+N(i))}rs!==Zu&&(rs=Xu),l=yr(l,i),f=a;do{switch(f.tag){case 3:u=l,f.effectTag|=4096,f.expirationTime=t;var w=Ar(f,u,t);ln(f,w); break e;case 1:u=l;var E=f.type,k=f.stateNode;if(0===(64&f.effectTag)&&("function"==typeof E.getDerivedStateFromError||null!==k&&"function"==typeof k.componentDidCatch&&(null===ms||!ms.has(k)))){f.effectTag|=4096,f.expirationTime=t;var _=Ir(f,u,t);ln(f,_);break e}}f=f.return}while(null!==f)}ts=no(ts)}catch(e){t=e;continue}break}}function Yr(){var e=Bu.current;return Bu.current=Cu,null===e?Cu:e}function Gr(e,t){eus&&(us=e)}function Jr(){for(;null!==ts;)ts=to(ts)}function eo(){for(;null!==ts&&!Gl();)ts=to(ts)}function to(e){var t=Fu(e.alternate,e,ns);return e.memoizedProps=e.pendingProps,null===t&&(t=no(e)),qu.current=null,t}function no(e){ts=e;do{var t=ts.alternate;if(e=ts.return,0===(2048&ts.effectTag)){if(t=br(t,ts,ns),1===ns||1!==ts.childExpirationTime){for(var n=0,r=ts.child;null!==r;){var o=r.expirationTime,a=r.childExpirationTime;o>n&&(n=o),a>n&&(n=a),r=r.sibling}ts.childExpirationTime=n}if(null!==t)return t;null!==e&&0===(2048&e.effectTag)&&(null===e.firstEffect&&(e.firstEffect=ts.firstEffect),null!==ts.lastEffect&&(null!==e.lastEffect&&(e.lastEffect.nextEffect=ts.firstEffect),e.lastEffect=ts.lastEffect),1e?t:e}function oo(e){var t=qt();return Vt(99,ao.bind(null,e,t)),null}function ao(e,t){do lo();while(null!==gs);if((Ju&(Wu|$u))!==Hu)throw Error(r(327));var n=e.finishedWork,o=e.finishedExpirationTime;if(null===n)return null;if(e.finishedWork=null,e.finishedExpirationTime=0,n===e.current)throw Error(r(177));e.callbackNode=null,e.callbackExpirationTime=0,e.callbackPriority=90,e.nextKnownPendingLevel=0;var a=ro(n);if(e.firstPendingTime=a,o<=e.lastSuspendedTime?e.firstSuspendedTime=e.lastSuspendedTime=e.nextKnownPendingLevel=0:o<=e.firstSuspendedTime&&(e.firstSuspendedTime=o-1),o<=e.lastPingedTime&&(e.lastPingedTime=0),o<=e.lastExpiredTime&&(e.lastExpiredTime=0),e===es&&(ts=es=null,ns=0),1u&&(c=u,u=l,l=c),c=Ue(w,l),f=Ue(w,u),c&&f&&(1!==k.rangeCount||k.anchorNode!==c.node||k.anchorOffset!==c.offset||k.focusNode!==f.node||k.focusOffset!==f.offset)&&(E=E.createRange(),E.setStart(c.node,c.offset),k.removeAllRanges(),l>u?(k.addRange(E),k.extend(f.node,f.offset)):(E.setEnd(f.node,f.offset),k.addRange(E)))))),E=[];for(k=w;k=k.parentNode;)1===k.nodeType&&E.push({element:k,left:k.scrollLeft,top:k.scrollTop});for("function"==typeof w.focus&&w.focus(),w=0;w=t&&e<=t}function To(e,t){var n=e.firstSuspendedTime,r=e.lastSuspendedTime;nt||0===n)&&(e.lastSuspendedTime=t),t<=e.lastPingedTime&&(e.lastPingedTime=0),t<=e.lastExpiredTime&&(e.lastExpiredTime=0)}function Co(e,t){t>e.firstPendingTime&&(e.firstPendingTime=t);var n=e.firstSuspendedTime;0!==n&&(t>=n?e.firstSuspendedTime=e.lastSuspendedTime=e.nextKnownPendingLevel=0:t>=e.lastSuspendedTime&&(e.lastSuspendedTime=t+1),t>e.nextKnownPendingLevel&&(e.nextKnownPendingLevel=t))}function No(e,t){var n=e.lastExpiredTime;(0===n||n>t)&&(e.lastExpiredTime=t)}function Po(e,t,n,o){var a=t.current,i=Fr(),l=su.suspense;i=jr(i,a,l);e:if(n){n=n._reactInternalFiber;t:{if(J(n)!==n||1!==n.tag)throw Error(r(170));var u=n;do{switch(u.tag){case 3:u=u.stateNode.context;break t;case 1:if(It(u.type)){u=u.stateNode.__reactInternalMemoizedMergedChildContext;break t}}u=u.return}while(null!==u);throw Error(r(171))}if(1===n.tag){var s=n.type;if(It(s)){n=Dt(n,s,u);break e}}n=u}else n=Al;return null===t.context?t.context=n:t.pendingContext=n,t=on(i,l),t.payload={element:e},o=void 0===o?null:o,null!==o&&(t.callback=o),an(a,t),Dr(a,i),i}function Oo(e){if(e=e.current,!e.child)return null;switch(e.child.tag){case 5:return e.child.stateNode;default:return e.child.stateNode}}function Ro(e,t){e=e.memoizedState,null!==e&&null!==e.dehydrated&&e.retryTime