Search

Background: In COVID-19 intensive care unit (ICU)–admitted patients, multiorgan acute complications lead to long-lasting sequelae. The aim of this study was to assess (1) changes in chest CT, pulmonary function test (PFT), functional capacity (6-minute walking distance test (6MWT)), and health-related quality of life (HR-QoL) among ICU COVID-19 survivors at 3, 6, and 12 months after ICU discharge and (2) predictors of persistent impairment/improvement in 6MWT and HR-QoL. Methods: ICU COVID-19 survivors were prospectively included. Outcomes at 3, 6, and 12 months included PFT, 6MWT, respiratory muscle strength (RMS), HR-QoL (SF-36), Medical Research Council dyspnea scale (mMRC), and post-COVID Functional Status scale. Results: Eighty-seven survivors were included, from June 3, 2020, to September 2, 2021. At 12 months, 50% of PFT were normal, 46% were restrictive, and 22% showed reduced diffusing capacity for carbon monoxide (DLCO). Impaired DLCO was associated with ICU length of stay and age. In mixed linear model analysis, improvements in RMS and mMRC persisted over time regardless of the adjustments applied (P ≤ .050). SF-36 improved in parallel with FEV1 and 6MWT between 3 and 12 months (P ≤ .044), while increment in DLCO correlated with changes in FEV1 and total lung capacity (TLC) (p ≤ 0.026). Conclusions: This longitudinal study demonstrated that improvements in SF-36 occur in parallel with improvements in FEV1 and 6MWT between 3 and 12 months post-ICU discharge in a sample of critically ill COVID-19 patients. However, PFT remained, however, abnormal in 50% of patients. Based on continued improvements observed from 3 to 12 months, it is anticipated that COVID-19 ICU patients will continue to recover similarly to ARDS patients.

Introduction: Despite improved management of patients with COVID-19, we still ignore whether pharmacologic treatments and improved respiratory support have modified outcomes for intensive care unit (ICU) surviving patients of the three first consecutive waves (w) of the pandemic. The aim of this study was to evaluate whether developments in the management of ICU COVID-19 patients have positively impacted respiratory functional outcomes, quality of life (QoL), and chest CT scan patterns in ICU COVID-19 surviving patients at 3 months, according to pandemic waves. Methods: We prospectively included all patients admitted to the ICU of two university hospitals with acute respiratory distress syndrome (ARDS) related to COVID-19. Data related to hospitalization (disease severity, complications), demographics, and medical history were collected. Patients were assessed 3 months post-ICU discharge using a 6 min walking distance test (6MWT), a pulmonary function test (PFT), a respiratory muscle strength (RMS) test, a chest CT scan, and a Short Form 36 (SF-36) questionnaire. Results: We included 84 ARDS COVID-19 surviving patients. Disease severity, complications, demographics, and comorbidities were similar between groups, but there were more women in wave 3 (w3). Length of stay at the hospital was shorter during w3 vs. during wave 1 (w1) (23.4 ± 14.2 days vs. 34.7 ± 20.8 days, p = 0.0304). Fewer patients required mechanical ventilation (MV) during the second wave (w2) vs. during w1 (33.3% vs. 63.9%, p = 0.0038). Assessment at 3 months after ICU discharge revealed that PFTs and 6MWTs scores were worse for w3 > w2 > w1. QoL (SF-36) deteriorated (vitality and mental health) more for patients in w1 vs. in w3 (64.7 ± 16.3 vs. 49.2 ± 23.2, p = 0.0169). Mechanical ventilation was associated with reduced forced expiratory volume (FEV1), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO), and respiratory muscle strength (RMS) (w1,2,3, p < 0.0500) on linear/logistic regression analysis. The use of glucocorticoids, as well as tocilizumab, was associated with improvements in the number of affected segments in chest CT, FEV1, TLC, and DLCO (p < 0.01). Conclusions: With better understanding and management of COVID-19, there was an improvement in PFT, 6MWT, and RMS in ICU survivors 3 months after ICU discharge, regardless of the pandemic wave during which they were hospitalized. However, immunomodulation and improved best practices for the management of COVID-19 do not appear to be sufficient to prevent significant morbidity in critically ill patients.

Abstract Background Obstructive sleep apnea syndrome (OSA) is currently recognized as an independent risk factor for hypertension, arrhythmia, coronary heart disease, stroke, and metabolic disorders (e.g. diabetes, dyslipidemia). In clinical practice, apnea-hypopnea index (AHI) is the marker used to classify disease severity and guide treatment. However, AHI alone does not sufficiently identify OSA patients at risk for cardiometabolic comorbidities. With this in mind, the aim of this retrospective study was to determine whether some polysomnographic parameters (e.g. apnea-hypopnea duration, sleep structure, nocturnal hypoxemia) are specifically associated with cardiometabolic comorbidities in OSA. Methods In this retrospective study, 1717 patients suffering from moderate/severe OSA were included between 2013 and 2017. Data on demographics, comorbidities, and polysomnographic characteristics were collected and analyzed to identify factors associated with cardiometabolic complications. Results The medical files of 1717 patients (68% male) were reviewed. The mean AHI was 43.1 +/− 27.7 with 57.3% of patients suffering from severe OSA, and 52% from at least one cardiovascular comorbidity (CVCo). Diabetes affected 22% of the patients and 27% exhibited dyslipidemia. Patients affected by CVCos were older, and more often women and non-smokers. These patients also had worse sleep quality, and a more marked intermittent/global nocturnal hypoxemia. With regard to diabetes, diabetics were older, more often non-smoker, non-drinker women, and were more obese. These patients also exhibited more severe OSA, especially in non-REM (NREM) sleep, worse sleep quality, and a more marked intermittent/global nocturnal hypoxemia. Dyslipidemia was more frequent in the absence of alcohol consumption, and was associated with OSA severity, decreased sleep quality, and longer AH in REM sleep. Conclusions This study identifies demographic and polysomnographic factors associated with cardiometabolic comorbidities. Patients (especially women) suffering from more severe OSA, longer sleep apneas and hypopneas, worse sleep quality, and marked intermittent/global nocturnal hypoxemia are more likely to develop cardiometabolic comorbidities. This should stimulate clinicians to obtain adequate treatment in this population.

This article presents an overview of the advancements that have been made in the use of photoplethysmography (PPG) for unobtrusive sleep studies. PPG is included in the quickly evolving and very popular landscape of wearables but has specific interesting properties, particularly the ability to capture the modulation of the autonomic nervous system during sleep. Recent advances have been made in PPG signal acquisition and processing, including coupling it with accelerometry in order to construct hypnograms in normal and pathologic sleep and also to detect sleep-disordered breathing (SDB). The limitations of PPG (e.g., oxymetry signal failure, motion artefacts, signal processing) are reviewed as well as technical solutions to overcome these issues. The potential medical applications of PPG are numerous, including home-based detection of SDB (for triage purposes), and long-term monitoring of insomnia, circadian rhythm sleep disorders (to assess treatment effects), and treated SDB (to ensure disease control). New contact sensor combinations to improve future wearables seem promising, particularly tools that allow for the assessment of brain activity. In this way, in-ear EEG combined with PPG and actigraphy could be an interesting focus for future research.

Abstract Background Phelan-McDermid syndrome (PMS) is a rare multisystem disease with global developmental delay and autistic features. Genetically, the disease is based on a heterozygous deletion of chromosome 22q13.3 with involvement of at least part of the SHANK3 gene or heterozygous pathogenic variants in SHANK3. Pathophysiologically, this syndrome has been regarded as a synaptopathy, but current data suggest an additional concept, since axonal functions of neurons are also impaired, thus, the specific pathophysiological processes in this disease are not yet fully understood. Since symptoms of the autism spectrum, regression, and stagnation in development occur, we investigated whether neuroinflammatory and neurodegenerative processes may also play a role. To this end, we analysed biomarkers in cerebrospinal fluid (CSF) and parameters from magnetic resonance imaging with high-resolution structural T1w volumetry and diffusion tensor imaging analysis in 19 Phelan-McDermid syndrome patients. Results CSF showed no inflammation but abnormalities in tau protein and amyloid-ß concentrations, however, with no typical biomarker pattern as in Alzheimer’s disease. It could be demonstrated that these CSF changes were correlated with integrity losses of the fibres in the corticospinal tract as well as in the splenium and dorsal part of the cingulum. High CSF levels of tau protein were associated with loss of integrity of fibres in the corticospinal tract; lower levels of amyloid-ß were associated with decreasing integrity of fibre tracts of the splenium and posterior cingulate gyrus. Volumetric investigations showed global atrophy of the white matter, but not the grey matter, and particularly not in temporal or mesiotemporal regions, as is typical in later stages of Alzheimer’s disease. Conclusions In summary, alterations of neurodegenerative CSF markers in PMS individuals could be demonstrated which were correlated with structural connectivity losses of the corticospinal tract, the splenium, and the dorsal part of the cingulum, which can also be associated with typical clinical symptoms in these patients. These findings might represent a state of dysfunctional processes with ongoing degenerative and regenerative processes or a kind of accelerated aging. This study should foster further clinical diagnostics like tau- and amyloid-PET imaging as well as novel scientific approaches especially in basic research for further mechanistic proof.

AbstractIn 2018, Ipas Bolivia launched an abortion self-care (ASC) community intervention with the goal of increasing access to supportive, well-informed abortion support provided by community agents (CAs). Between September 2019 and July 2020, Ipas conducted a mixed-methods evaluation to assess the reach, outcomes, and acceptability of the intervention. We used logbook data maintained by CAs to capture demographic characteristics and ASC outcomes of people supported. We also conducted in-depth interviews with 25 women who had received support and 22 CAs who had provided support. 530 people accessed ASC support through the intervention, most of whom were young, single, educated women accessing abortion in the first trimester. Among the 302 people who self-managed their abortions, 99% reported having a successful abortion. No women reported adverse events. All women interviewed expressed satisfaction with the support provided by the CA and, in particular, with the information, lack of judgement, and respect they felt from CAs. CAs spoke highly about their experience and viewed their participation as a way to increase people’s ability to exercise their reproductive rights. Obstacles included experiences of stigma, fears of legal repercussions, and difficulties dispelling misconceptions around abortion. Legal restrictions and abortion stigma continue to complicate access to safe abortion, and findings from this evaluation highlight important avenues for the effectiveness and expansion of ASC interventions, including legal support to people who have abortions and those who provide abortion support, building capacity of people as informed buyers, and ensuring that interventions reach rural and other often under-served people.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Abstract Background Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 and its ligand (PD-1/PD-L1) have become the current standard-of-care for advanced cancers. This novel therapeutic approach comes with its costs in the form of immune-related adverse events (irAE), including endocrinopathy. Case presentation A 63-year-old woman was diagnosed with a non-small cell lung carcinoma of the right superior lobe, cT3N2M0. She developed thyrotoxicosis followed by hypothyroidism induced by consolidation immunotherapy with durvalumab (anti-PD-L1). Analysis of the human leukocyte antigen (HLA) region showed HLA-DR4 (susceptible) and DR13 (protective). The possible mechanisms are subsequently discussed in detail. Conclusions The case of a patient with thyroiditis associated with the PD-L1 inhibitor durvalumab is described, highlighting the need for proactive monitoring of thyroid hormone levels. Identifying biomarkers associated with an increased risk of ICI-induced side effects (such as HLA) is of interest for better patient selection, optimal management and improved understanding of the mechanisms involved.

BackgroundAbortion stigma has been shown to influence provider attitudes around abortion and may decrease provider willingness to participate in abortion care, or lead some to obstruct care. However, this link remains understudied.MethodsThe present study uses baseline data collected through a cluster-randomized controlled trial in 16 public sector health facilities in South Africa in 2020. A total of 279 clinical and non-clinical health facility workers were surveyed. Primary outcome measures included: 1) willingness to facilitate abortion care in eight hypothetical scenarios, 2) facilitation of abortion care in the last 30 days, and 3) obstruction of abortion care in the last 30 days. Logistic regression models were used to assess the association between level of stigma as measured through the Stigmatizing Attitudes, Beliefs and Actions Scale (SABAS) and the primary outcomes.ResultsOverall, 50% of respondents in the sample were willing to facilitate abortion care in each of the eight scenarios, with differences in willingness based on the abortion client's age and personal situation in each scenario. Over 90% reported facilitating abortion care in the last 30 days, but 31% also reported having obstructed abortion care in the last 30 days. Stigma was significantly associated with willingness to facilitate abortion care and actual obstruction of abortion care in the last 30 days. Controlling for covariates, odds of willingness to facilitate abortion care in every scenario decreased with every one-point increase in SABAS score (reflecting more stigmatizing attitudes), and odds of obstructing abortion care increased with every one-point increase in SABAS score.ConclusionsLower abortion stigma on the part of health facility workers was associated with willingness to facilitate abortion access but not actual facilitation of abortion services. Higher abortion stigma was associated with actual obstruction of an abortion service in the last 30 days. Interventions to reduce stigma towards women seeking abortion, and particularly negative stereotyping, among all health facility staff is key to ensuring equitable and non-discriminatory access to abortion.Trial registrationRetrospectively registered on clinicaltrials.gov (ID: NCT04290832) on February 27, 2020.Plain english summaryThe link between stigma against women seeking abortion and decisions around whether to provide, abstain, or obstruct abortion care remains understudied. This paper assesses how stigmatizing beliefs and attitudes towards women seeking abortion in South Africa affects willingness to facilitate abortion care and actual facilitation or obstruction of abortion care in practice. A total of 279 clinical and non-clinical health facility workers were surveyed between February and March 2020. Overall, half of respondents in the sample were willing to facilitate abortion care in each of the eight scenarios, with important differences in willingness by scenario. Almost all respondents reported facilitating an abortion procedure in the last 30 days, but one in three also reported having obstructed abortion care in the last 30 days. More stigmatizing attitudes corresponded to decreased willingness to provide abortion care and increased odds of obstructing abortion care. Results show that stigmatizing attitudes, beliefs, and actions toward women who seek abortion shape how clinical and non-clinical staff in South Africa feel about their participation in abortion services and whether they obstruct this care. Facility staff hold great power in determining whose abortions are facilitated and whose are obstructed, resulting in stigma and discrimination being openly perpetuated. Continuous work to reduce stigma towards women seeking abortion among all health workers is key to ensuring equitable and non-discriminatory access to abortion for all.

Abstract Background Noninvasive prenatal testing (NIPT) is the most recent modality widely used in prenatal diagnostics. Commercially available NIPT has high sensitivity and specificity for the common fetal chromosomal aneuploidies. As future advancements in NIPT sequencing technology are becoming promising and more reliable, the ability to detect beyond aneuploidies and to expand detection of submicroscopic genomic alterations, as well as single-gene disorders might become possible. Case presentation Here we present a case of a 34-year-old pregnant woman, G2P1, who had NIPT screening which detected a terminal microduplication of 10.34 Mb on the long arm of chromosome 15 (15q26.1q26.3). Subsequent prenatal diagnostic testing including karyotype, microarray and fluorescence in situ hybridization (FISH) analyses were performed. Microarray testing confirmed and particularized a copy number gain of 10.66 Mb of the distal end of the long arm of chromosome 15. The G-banding cytogenetic studies yielded results consistent with unbalanced translocation between chromosome 15 and 18. To further characterize the abnormality involving the long arm of chromosome 18 and to map the genomic location of the duplicated 15q more precisely, FISH analysis using specific sub-telomeric probes was performed. FISH analysis confirmed that the extra duplicated segment of chromosome 15 is translocated onto the distal end of the long arm of chromosome 18 at band 18q23. Parental karyotype and FISH studies were performed to see if this unbalanced rearrangement was inherited from a healthy balanced translocation carrier versus being a de novo finding. Parental chromosomal analysis provided no evidence of a rearrangement between chromosome 15 and chromosome 18. The final fetal karyotype was reported as 46,XX,der(18)t(15;18)(q26.2;q23)dn. Conclusions In this case study, the microduplication of fetal chromosome 15q26.1q26.3 was accurately detected using NIPT. Our results suggest that further refinements in NIPT have the potential to evolve to a powerful and efficient screening method, which might be used to detect a broad range of chromosomal imbalances. Since microduplications and microdeletions are a potential reportable result with NIPT, this must be included in pre-test counseling. Prenatal diagnostic testing of such findings is strongly recommended.

El sangrado uterino anormal representa al menos un tercio de las consultas ginecológicas por causa de los síntomas de esta patología. A pesar de que no es un diagnóstico en sí, el mismo se presenta como una variación en la duración, variabilidad, volumen y frecuencia del sangrado durante la menstruación de la paciente. Al manifestarse, se debe considerar su probable etiología, por medio del acrónimo conocido como PALM-COEIN, el cual se basa en causas estructurales y no estructurales que originan el sangrado uterino anormal. Así mismo poder direccionar el diagnóstico, según las características del sangrado en la paciente.

NaX is an atypical member of the voltage-gated sodium channel family that may contribute to Na+ homeostasis. Here, the authors describe the structural and functional attributes of the human NaX channel to reveal new insights into its physiology.

Resumen Antecedentes El mal uso de la objeción de conciencia (OC) es una barrera importante para el acceso al aborto aún cuando es legal, en muchos países, especialmente en países en América Latina. Examinamos los motivos de la negación de servicios de aborto legal en México y Bolivia e identificamos formas de mitigar el uso indebido de la OC. Métodos Realizamos 34 entrevistas a profundidad y 12 discusiones en grupo focal en dos estados en México y cuatro departamentos en Bolivia. Los resultados fueron codificados y categorizados utilizando un enfoque de análisis temático. Resultados La negación de servicios de aborto basados ​​en la OC está muy extendida en los establecimientos de salud en México y Bolivia y se emplea principalmente por razones distintas a las consideraciones morales, religiosas o éticas. Las principales razones para la negación de servicios basados ​​en la OC son la falta de conocimiento sobre las leyes relacionadas con el aborto y el temor a problemas legales en la prestación de servicios de aborto. Por el contrario, la razón principal para proporcionar servicios es cumplir con las leyes pertinentes. Negar servicios bajo la apariencia de OC impacta negativamente a las personas embarazadas y a los equipos de atención médica, incluidas menos opciones de aborto seguro y mayor carga de trabajo y estigma, respectivamente. La mayoría de los encuestados mencionaron la capacitación y educación sobre la ley del aborto como la principal forma de mitigar los impactos negativos del uso indebido de la OC. Conclusiones Para parte del personal de salud, conocer, comprender y cumplir la ley es motivo suficiente para proporcionar servicios de aborto. Las personas que se oponen debido a la falta de conocimiento sobre las leyes y el miedo a los problemas legales representan una población clave que puede ser sensibilizada y equipada con la información y los recursos necesarios para proporcionar servicios de aborto legal.

Phelan-McDermid syndrome is an inherited global developmental disorder commonly associated with autism spectrum disorder. Due to a significantly increased radiosensitivity, measured before the start of radiotherapy of a rhabdoid tumor in a child with Phelan-McDermid syndrome, the question arose whether other patients with this syndrome also have increased radiosensitivity. For this purpose, the radiation sensitivity of blood lymphocytes after irradiation with 2Gray was examined using the G0 three-color fluorescence in situ hybridization assay in a cohort of 20 patients with Phelan-McDermid syndrome from blood samples. The results were compared to healthy volunteers, breast cancer patients and rectal cancer patients. Independent of age and gender, all but two patients with Phelan-McDermid syndrome showed significantly increased radiosensitivity, with an average of 0.653 breaks per metaphase. These results correlated neither with the individual genetic findings nor with the individual clinical course, nor with the respective clinical severity of the disease. In our pilot study, we saw a significantly increased radiosensitivity in lymphocytes from patients with Phelan-McDermid syndrome, so pronounced that a dose reduction would be recommended if radiotherapy had to be performed. Ultimately, the question arises as to the interpretation of these data. There does not appear to be an increased risk of tumors in these patients, since tumors are rare overall. The question, therefore, arose as to whether our results could possibly be the basis for processes, such as aging/preaging, or, in this context, neurodegeneration. There are no data on this so far, but this issue should be pursued in further fundamentally based studies in order to better understand the pathophysiology of the syndrome.

Objectives: Dilation and curettage is an outdated abortion procedure no longer recommended by the World Health Organization. However, use of dilation and curettage remains high in some countries, including Mexico. We aim to understand the factors that contribute to persistent use of dilation and curettage in Mexico. Methods: We conducted a mixed-methods study in two phases: (1) secondary quantitative data analysis from 40 Ipas-supported public hospitals in Mexico and (2) 28 in-depth interviews in 9 Ipas-affiliated hospitals with doctors, nurses, and hospital administrators. Results: Among our sample, 41% of abortions less than 13 weeks performed in 2019 were treated with dilation and curettage, while this increased to 67% of abortions at or above 13 weeks. Only 18% of induced abortions were performed with dilation and curettage compared to 44% of post-abortion care procedures. The main factor identified as determining use of dilation and curettage in in-depth interviews was availability of abortion supplies, both in terms of cleaning, storage, and maintenance of supplies and in the budgeting and procurement of supplies. Other factors included confidence in the efficacy of other methods, attitudes toward different methods, skill and training, and perceived benefits to patients. Conclusion: Ensuring supplies for recommended abortion methods are available is a key lever for any intervention aimed at reducing dilation and curettage use. However, as the doctor performing the abortion decides which method to use, individual factors such as lack of skill and mistrust in other procedures can become a particularly obstinate barrier to recommended method use. Localizing decision-making power in the hands of doctors is problematic in that it places the doctor’s preference above that of the person receiving the abortion. It is important to look deeply at the power structures that contribute to doctor-oriented models of abortion care.

The COVID-19 pandemic led overburdened health care systems to deprioritize essential sexual and reproductive healthcare, including abortion and contraception care, while accelerating shifts in healthcare delivery to digital technologies. However, in many countries, including Pakistan, inequalities in access to digital technologies remain, presenting an opportunity for interventions that both increase access to deprioritized sexual and reproductive health and rights (SRHR) services and overcome the digital divide in delivering digital solutions to those in need of SRHR services. In June 2020, Ipas Pakistan partnered with Sehat Kahani (SK), a local health care NGO and telehealth service, and an existing network of Lady Health Workers (LHWs) to launch a novel hybrid telemedicine-community accompaniment pilot. The model linked women via LHWs with mobile devices to online providers for telemedicine consultations for SRH, including abortion services, contraception, and other gynecological consultations. In June 2020, we trained 98 LHWs and 22 telehealth doctors. Between June 2020 and March 2021, a total of 176 women were referred by LHWs for telehealth consultations. Among women who received abortion services, nearly all (90%) reported complete uterine evacuation. No serious adverse events were reported. Overall satisfaction was high; 81% reported being satisfied, and 86% said it is likely they would recommend the telehealth service to others. Data show that the provision of SRHR services via a telehealth-accompaniment model can be successfully implemented in Pakistan. Outcome data show high satisfaction and good clinical outcomes for women accessing care through this model. However, more data are needed to understand the full potential of this model. Barriers to digital health models, such as poor or inconsistent internet access, remain in places like Pakistan, especially in rural settings. This approach has its limitations but should be considered as an option in settings with similarly established community health networks and inequitable access to digital health.

Immunotherapy has revolutionized medical oncology by providing durable responses in a number of malignancies. Programmed death-1 inhibitors are rapidly gaining popularity and increased use. They are also associated with a variety of adverse reactions. Although PD-1 inhibitors are generally tolerated relatively well and usually have milder side effects than chemotherapy, the risk remains for immune mediated adverse reactions. Caution should be exercised when re-challenging grade three or four adverse effects with the same agent or a different agent of the same class. The reemergence of a previous toxicity may occur or new toxicity. Immune related adverse events affect the nervous system and effects are generally mild however this case describes an exotic, fatal outcome in a patient with severe enteric neuropathy.

Introduction: Microdeletions in the chromosomal region 2q34 and its neighboring regions lead to a phenotypic spectrum including autism, intellectual disability, and epilepsy. Up to now, only few affected patients have been reported. Therefore, the genetic pathogenesis is not completely understood. One of the most discussed candidate genes in this context is MAP2, a gene responsible for microtubule polymerization and neurite outgrowth.Materials and Methods: We present a 4.5-year-old male patient with epilepsy, mild developmental delay, and behavioral abnormalities. SNP-Array analysis was performed to search for pathogenic copy number variations.Results: SNP-Array analysis revealed a 1.5 Mb de novo microdeletion on the long arm of chromosome 2 (2q34). The identified microdeletion included the candidate genes UNC80, LANCL1, and most importantly MAP2.Discussion: The reported microdeletion identified in this patient is the smallest one described in the literature so far spanning MAP2 next to UNC80 and LANCL1. In this context MAP2 is the most important candidate gene concerning neuronal development and its function should be further examined.