Fetal impact of cystic fibrosis transmembrane conductance regulator modulator use during assisted and natural reproduction and partner pregnancy in men with cystic fibrosis

Background: Increasing availability of highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapy (HEMT) has improved the quality of life and long-term prognosis for many people with CF. Thus, more people with CF are considering parenthood. Almost all menwith CF (MwCF) are infertile because of congenital bilateral absence of the vas deferens (CBAVD). Based on CF animal models, CBAVD occurs early in gestation and is unlikely to be reversible using HEMT, but assisted reproductive techniques (ARTs) can enable MwCF to father children using the sperm in their testes. Animal reproductive models suggest no HEMT teratogenicity, and the amount of exposure of the fetus to HEMT via absorption of seminal fluid through the vaginal wall is predicted to be negligible, although to ensure no sperm exposure to HEMT, the life span of sperm would require MwCF to discontinue CFTR modulators for approximately 3 months before ART. Because abrupt discontinuation of CFTR modulators may result in health decline, MwCF and their providers must consider all potential risks. There are no published data in MwCF regarding use of HEMT during conception and partner pregnancy. Method(s): Beginning in August 2021, CF center staff in the United States, United Kingdom, and Australia completed a two-page anonymous questionnaire regarding MwCF who used CFTR modulators during ART (sperm retrieval and in vitro fertilization) or natural conception with subsequent partner pregnancy. Result(s): Providers have submitted 34 surveys for MwCF on CFTR modulators whose partner became pregnant after use of ART (n = 32) or natural conception (n = 2). The median age of the samplewas 32 (range 24- 43). Fifteen were homozygous for F508del, median percentage predicted forced expiratory volume in 1 second was 76% (range (22-111%), and median body mass index was 24 kg/m2 (range 18.5-32.1). Twenty-three were taking elexacaftor/tezacaftor/ivacaftor. The median time that MwCF were taking CFTR modulators before partner conception was 18 months (range 0-82). One newly diagnosed man initiated HEMT after sperm retrieval. Four MwCF stopped CFTR modulators before sperm retrieval, one of whom experienced pulmonary decline. None of the 19 MwCF whose condom use during pregnancy was known used condoms. Fetal complications in partners of MwCF included three first-trimester miscarriages, two* COVID, two breech presentation, two* vaginal bleeding, and one vasa previa. None of the complications were deemed definitively related to use of CFTR modulators. One MwCF experienced testicular infection after sperm retrieval#. Postpartum complications included three# infants with hypoxemia requiring neonatal intensive care unit stay, three maternal blood loss, one forceps delivery, and one caesarean section. No congenital anomalies were reported for any infant. (*/# overlap). Conclusion(s): Use of CFTR modulator therapy during partner conception and pregnancy in 34 MwCF has not resulted in higher-than-expected miscarriage rates or congenital anomalies. Providers should consider the risk to the health of MwCF combined with the lack of teratogenicity in animal reproductive models and limited safety data in the human fetus before discontinuing CFTR modulators before ART or natural partner conception. Survey collection is ongoing;results will be updated for presentationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved

Dorsal pancreatic agenesis: Case report and topic review

Complete agenesis of the dorsal pancreas (ADP) is an exceedingly rare congenital anomaly, compatible with life. It is frequently asymptomatic and usually incidentally diagnosed. In symptomatic cases, the clinical manifestations vary from abdominal pain, pancreatitis and diabetes mellitus to exocrine insufficiency with steatorrhea. We present a case report of a 28-year-old female with ADP, diagnosed incidentally during radiological evaluation for hyperglycemias during a SARS-CoV2 concomitant infection. Magnetic resonance cholangiopancreatography confirmed the absence of neck, body and tail of the pancreas. Familiarization with pancreatic embryogenesis, as well as the clinical presentation and main radiological characteristics of its anomalies is important for the proper diagnosis of these malformations.

RARE CASE OF MASSIVE DVT AFTER MRNA COVID-19 VACCINATION IN A PATIENT WITH CONGENITAL IVC ANOMALY

SESSION TITLE: Thrombosis Jamboree: Rare and Unique Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Deep vein thrombosis (DVT) formation is widely recognized as Virchow's Triad of hypercoagulability, venous stasis, and endothelial injury. Based on this definition, congenital aberrations of the inferior vena cava (IVC) such as atresia or coarctation classify as major risk factors to incite a DVT (1). A congenital IVC anomaly with evidence of post-COVID-19 vaccination hypercoagulability (2) suggests a risk association with thrombotic episodes. We present a case of congenital IVC interruption with development of a DVT nine days after Pfizer COVID-19 booster administration. While it is known that IVC anomalies may contribute to DVT development (1), there is scarce data identifying a COVID-19 mRNA vaccine as a direct source of massive DVT in a young adult. CASE PRESENTATION: A 28 year old male with a history of repaired coarctation of the aorta presented with severe right thigh pain that began days after the Pfizer COVID-19 booster. Four days prior, an outpatient ultrasound (US) was negative for DVT. Physical exam revealed a dusky right foot with good distal pulses. Sensation was intact throughout. The left lower extremity (LE) had no edema or tenderness. An US of the right LE showed a DVT extending from the common femoral vein to the posterior tibial vein and DVT of the greater saphenous and deep femoral vein. Left LE US showed an anterior tibial DVT. Attempted thrombolysis was made with tissue plasminogen activator therapy and thrombectomy. Given the patient's atretic IVC anatomy, some residual clot remained in the common iliac vein, and was treated with anticoagulation therapy. After two extensive surgical lyses and aggressive medical lysis, the DVT's were resolved and the patient slowly improved. Upon follow up, he is feeling much better with no further pain. Ultimately this patient will require lifelong anticoagulation and may require an IVC stent to prevent future thrombotic events. DISCUSSION: Coarctation of the aorta is a common congenital heart defect and is often coupled with additional cardiovascular anomalies (1). In our patient, imaging showed a small and near-occluded IVC, which predisposed him to vasculitic events. There is no literature describing a massive DVT in a young adult patient within days of an mRNA COVID-19 vaccine. While these thrombotic events are rare (2), this report portrays one case in which the Pfizer COVID-19 mRNA vaccine may have prompted a vascular event in a susceptible patient. CONCLUSIONS: It has been previously established that congenital IVC anomalies may contribute to increased risk of DVT (1). In this case, we observe an association of the mRNA COVID-19 vaccine with massive DVT in a young male. While this is not meant to discourage patients with congenital IVC anomalies from receiving the COVID vaccine series, it prompts the need for open discussion with healthcare providers to discuss possible adverse effects. Reference #1: Chee, Y.-L., Culligan, D.J. and Watson, H.G. Inferior vena cava malformation as a risk factor for deep venous thrombosis in the young. British Journal of Haematology. 2001;114:878-880. doi.org/10.1046/j.1365-2141.2001.03025.x Reference #2: Bilotta C, Perrone G, Adelfio V, et al. COVID-19 Vaccine-Related Thrombosis: A Systematic Review and Exploratory Analysis. Front Immunol. 2021;12:729251. doi:10.3389/fimmu.2021.729251 Reference #3: Ruggeri M, Tosetto A, Castaman G, Rodeghiero F. Congenital absence of the inferior vena cava: a rare risk factor for idiopathic deep-vein thrombosis. The Lancet. 2001;357(9254):441. doi.org/10.1016/S0140-6736(00)04010-1 DISCLOSURES: No relevant relationships by Melanie Krongold no disclosure on file for Majed Samarneh;No relevant relationships by Elena Tran No relevant relationships by Lakshmi Sheetala Vijaya

A new perspective of hypothalamic disease: Shapiro's syndrome.

Shapiro's syndrome (SS) is characterized by spontaneous periodic hypothermia. It occurs to patients regardless of age or sex. To date, <60 cases have been reported worldwide. Current knowledge of the disease is limited to clinical feature since the pathogenesis and etiology are still controversial. In this review, the clinical characteristics, pathological mechanism, and possible etiology of the syndrome were reviewed to improve the clinical understanding of the disease.

Setting up an e-learning program for male patients presenting cystic fibrosis (CF) infertility

98% of male CF patients have congenital bilateral absence of the vas deferens leading to hypofertility. CF patients’ life expectancy and quality of life have improved, especially with CFTR modulators, and access to paternity is an increasingly unavoidable subject. In 2020, we built a therapeutic education program to improve patients’ knowledge and facilitate their decision-making regarding spermatozoid’s conservation ( A-1117-0011-00309 43rd ECFC). Development of e-health and the context of the COVID-19 pandemic led us to build an e-learning program. Methods and objectives: Our working group, including CF patients and parents, teamed up with an e-learning solutions expert agency. We wanted to facilitate access to training and better respect patients’ receptiveness to receive this sensitive information. The patient could review on his own after a face-to-face session. The objective was to broaden access for the parents and partners of boys and men with CF and provide a solid basis for discussion between patients and caregivers. Results: This e-learning training is available on PC and Smartphone. Patient data are protected according to French regulations. The training consists of 5 independent modules 1: Initial knowledge self-assessment, 2: CF male hypofertility, 3: Spermogram with a motion design on its practical modalities, 4: Surgical collection of sperm, 5: Video testimony of a patient, and a satisfaction questionnaire. Discussion: We started the program in June 2020 with voluntary patients. We submitted this work to the GETHEM (French National Therapeutic Education Working Group) in June 2021, which validated its promotion at the national level in October 2021. This program has been well received but the number of connections remains low (17 professional, 10 patients). The subject requires an adoption time by caregivers, and will re-launch in 2022. An additional module concerning genetic transmission of the disease to children as a CF parent is underway.

Bilateral proximal deep vein thrombosis and COVID-19 in a patient with absence of inferior vena cava: A case report and review of literature.

Bilateral proximal deep vein thrombosis (DVT) in the lower extremities of young patients should raise suspicion over pro-thrombotic conditions and venous anatomical abnormalities, even in the presence of other precipitating factors, such as viral infection. The authors present a 33-year-old man with bilateral DVT and absence of inferior vena cava (AIVC), who also had concurrent COVID-19, and discuss the management of this patient.

Congenital Portosystemic Shunts in Children: A Case Series From Single Centre

Background: Congenital portosystemic venous shunts (CPSS) are uncommon foetal vascular developmental anomalies where splanchnic venous flow bypasses liver. Four cases of CPSS are reported at our centre. Case Summary (1) Eight years old female child presented with Dengue with no features of chronic liver disease and normal liver function test (LFT). Ultrasonography (UGS) abdomen reported an incidental finding of abnormal vascular shunt in liver. Further imaging revealed an anastomosis between portal vein and intrahepatic part of inferior vena cava (IVC), hypoplastic portal vein and multiple nodules in bilateral liver lobes. Interventional Radiologist closed the anastomosis using vascular plug. Child sustained the procedure well. (2) Two months old female patient presented with high GGTP cholestasis, dysmorphism and deranged LFT. On USG abdomen there was intrahepatic portosystemic shunt. MDCT abdomen revealed 2 vascular shunts between left portal vein to middle hepatic vein and left portal vein. Cholestasis responded with symptomatic treatment, hence being followed-up for observation till 1year of age for complications and possibility of spontaneous closure. (3) Twenty-two days old, full term female child presented with convulsions and high GGTP cholestasis with multiple hematomas in brain. LFTs were deranged. 2D-ECHO showed small PFO. USG abdomen suggested a channel between left portal vein and hepatic vein. Patient tested COVID positive hence quarantined now and further evaluation is awaited. (4) One day old, late preterm male baby presented with respiratory distress and pulmonary hypertension with antenatal scan suggesting ductus venous agenesis with hepatic vascular malformation. Patient developed cholestasis with deranged LFT. 2D-ECHO showed PDA and ASD. MDCT abdomen revealed connection between main portal vein and intrahepatic IVC. Conclusions: CPSS has heterogeneous presentation. It can be diagnosed antenatal or postnatal, may be asymptomatic or may present as neonatal cholestasis and may be associated with anomalies. Management may vary from case to case and mainly depends on complications and age of presentation.

A case of direct hyperbilirubinemia in the setting of multisystem inflammatory syndrome in children with incidental gallbladder agenesis

Case Report In April 2020, cases of multisystem inflammatory syndrome in children(MIS-C) were reported from the UK as clinical presentations similar to incomplete Kawasaki and toxic shock syndrome in the setting of COVID-19. MIS-C is a rare but significant complication of COVID-19. We present the case of direct hyperbilirubinemia associated with MIS-C with incidentally discovered gallbladder agenesis. Case presentation A 16-year-old male presented with fever, epigastric pain, jaundice, and rash. He tested positive for SARS-CoV-2 one month prior, improved clinically, but developed fever one day before presentation. Physical exam revealed a diffuse maculopapular rash, jaundice, and right upper quadrant tenderness. Vitally stable. Work up for MIS-C revealed positive SARS-CoV-2, lymphopenia, ESR 23 mm/hr, fibrinogen 552 mg/dl, CRP 8.94 mg/ dL. Troponin, BNP, and coagulation profile were normal. Echo and CXR were unremarkable. CMP showed ALT 242 IU/L, AST 145 IU/L, total bilirubin of 5.7 mg/dL with direct bilirubin of 3.9 mg/dL, GGT 178 IU/L, consistent with obstructive jaundice. Workup for autoimmune hepatitis and viral hepatitis was negative. US right upper quadrant was done to rule out an obstructive pathology, which was normal except that it showed an absent gallbladder. MRCP and HIDA scan also showed no obstructive pathology and confirmed gallbladder agenesis. With no clear reason for direct hyperbilirubinemia, treatment for mild MIS-C was initiated with IV dexamethasone. Repeat blood work after 24 hours showed down trending bilirubin levels and stable liver enzymes, patient was discharged shortly afterwards. At one month follow up, liver enzymes and bilirubin normalized. Discussion Presentations of MIS-C vary with the most common being persistent fever along with gastrointestinal, respiratory, neurological, skin, and/or cardiac involvement. Acute hepatitis with elevated liver enzymes is a well-documented lab finding but direct hyperbilirubinemia is rare. Another interesting finding in our case was gallbladder agenesis, which is a rare congenital anomaly (incidence 10-65 per 100,000). Conclusion We highlight in our case report that cholestatic jaundice, despite being a very rare manifestation of MIS-C, can still occur. A multidisciplinary approach should be taken when treating such patients including GI, cardiology, rheumatology, and infectious disease.

An early complication in patient with CoViD19 pneumonia

Background: In December 2019, many cases of atypical pneumonia with unknown etiology were reported in China. Later on, a new coronavirus was identified, named SARS-CoV-2. We present a case of SARS-CoV-2 pneumonia complicated by spontaneous pneumomediastinum (SPM), pneumothorax (PNX) and subcutaneous emphysema (SCE) without the use of an invasive or noninvasive positive pressure ventilator. Presentation of the case: A 42-year-old man with moderate dyspnea arrived at the DEA. He reported infection with SARS-CoV-2 from a week. He reported no medical history. At the entrance the patient was lucid, oriented and cooperative. The B.P. was 125/75 with sinus rhythm with pulse 75 bpm, apyretic, SpO2 88% on A.A. To DEA showed examinations: D-Dimer 549, fibrinogen 850, VES 75, PCR 8.33, LDH 295. The EGA (Reservoir 90%) detected: pO2 60.7 mmHg, pCO2 36.3, pH 7.47, SpO2 92% and P/F 67,4. The Rx thorax showed multiple hazy parenchymal opacities in the lower lobar seat bilaterally. He was submitted to therapy based on dexamethasone, fluid therapy, antibiotics, enoxaparin. After 36 hours, he presented progressive deterioration of respiratory function and chest CT showed: SPM, PNX, SCE. After two days he died. Conclusions: In many CoViD-19 studies the incidence of SPM, PNX, SCE is rare. The peculiarity of this case report is given by the serious SPM, PNX, SCE as an early complication in the absence of lung comorbidities, cough, consume alcohol, smoke tobacco or use recreational drugs. This suggests that others processes related to CoViD-19 might be the mechanism of air leak that progress to SPM, PNX, SCE.

Secondary pyosalpinx after reconstructive surgery of vaginal agenesis patient with bilateral hematosalpinx: A case report.

INTRODUCTION AND IMPORTANCE: Congenital or hypoplasia vaginal agenesis is a very rare condition caused by the failure of developmental Mullerian ducts. The prevalence is 0.001%-0.025% populations. This condition often misdiagnosed because the symptom does not appear. Acute symptoms such as abdominal pain may occur due to the obstruction of retrograde menstrual flow. In this case, we presented a case complex management of vaginal atresia with pyosalpinx, hematometra and bilateral hematosalpinx. PRESENTATION OF CASE: A 12 years old teenager, non-sexually active, complained cyclic abdominal pain that worsening in seven months before admission. Patient never had menstrual blood flow during her life. Patient was diagnosed with hematometra, hematocolpos, bilateral hematosalpinx and distal vaginal agenesis. Amnion graft neovagina was performed. Five days after surgery, patient started to have fever. On the seventh days after surgery, amnion graft was removed. The next two days patient still had fever. Because of continuous fever, patient was test of COVID 19. The result was positive. On the eleventh days after the first surgery, patient complained abdominal pain VAS 3-4. Patient was diagnosed with pyosalpinx by ultrasound examination. Laparotomy was done performing adhesiolysis, bilateral salpingectomy, and omentectomy. DISCUSSION: In our case vaginal reconstruction surgery from vaginal approach has been done without management of the bilateral hematosalpinx because the consideration of small caliber of bilateral hematosalpinx. But then complications were developed when vaginal canal was opened, bilateral hematosalpinx were transformed into bilateral pyosalpinx and continue to developed into bilateral tubal abscess. We assume during this process, the bacteria from vagina could fastly infecting the blood and transformed it into pus and grew until tubal abscess. CONCLUSION: The surgical intervention in vaginal agenesis must be considered as a treatment and not only focus on the reconstruction. Laparoscopy or laparotomy may offered as options for combination treatment with vaginal approach reconstructive surgery for vaginal agenesis with obstruction complications such as hematometra and hematosalpinx to prevent the worst condition like ascending infection or misdiagnosed other severe conditions.