Severe combined immunodeficiency diagnosis and genetic defects.

Severe combined immunodeficiency (SCID) is a rare and life-threatening genetic disorder that severely impairs the immune system's ability to defend the body against infections. Often referred to as the "bubble boy" disease, SCID gained widespread recognition due to the case of David Vetter, a young boy who lived in a sterile plastic bubble to protect him from germs. SCID is typically present at birth, and it results from genetic mutations that affect the development and function of immune cells, particularly T cells and B cells. These immune cells are essential for identifying and fighting off infections caused by viruses, bacteria, and fungi. In SCID patients, the immune system is virtually non-existent, leaving them highly susceptible to recurrent, severe infections. There are several forms of SCID, with varying degrees of severity, but all share common features. Newborns with SCID often exhibit symptoms such as chronic diarrhea, thrush, skin rashes, and persistent infections that do not respond to standard treatments. Without prompt diagnosis and intervention, SCID can lead to life-threatening complications and a high risk of mortality. There are over 20 possible affected genes. Treatment options for SCID primarily involve immune reconstitution, with the most well-known approach being hematopoietic stem cell transplantation (HSCT). Alternatively, gene therapy is also available for some forms of SCID. Once treated successfully, SCID patients can lead relatively normal lives, but they may still require vigilant infection control measures and lifelong medical follow-up to manage potential complications. In conclusion, severe combined immunodeficiency is a rare but life-threatening genetic disorder that severely compromises the immune system's function, rendering affected individuals highly vulnerable to infections. Early diagnosis and appropriate treatment are fundamental. With this respect, newborn screening is progressively and dramatically improving the prognosis of SCID.

Psychotherapeutic interventions for depressive symptoms in older adults in a community setting: a systematic review protocol.

Depression is a prevalent illness among the elderly, so psychotherapeutic interventions are needed to promote health and quality of life. This literature review aims to identify trials of any psychotherapeutic interventions aimed at reducing depressive symptoms in older adults. A systematic literature review with a meta-analysis will be carried out. The following databases will be searched: CINAHL Plus with Full Text, MedicLatina, MEDLINE with Full Text, and Psychology and Behavioral Sciences Collection. To minimize bias, four reviewers will independently assess the inclusion of studies. The fifth reviewer will be responsible for disaggregating inclusion and exclusion between two authors. The results of the analysis will be grouped in a table with the characteristics of the included studies, including author, year, sample, objectives, methods, assessment instruments, psychotherapeutic interventions, results, follow-up and a data compilation scheme. This scientific article is a systematic review protocol for which the data has already been extracted and is being analyzed. Examples of possible strategies to include cognitive restructuring and mental health programs for older adults in community settings. With this clear and direct identification of psychotherapeutic interventions, it will be clearer for mental health professionals to be able to intervene effectively to promote the mental health and well-being of older adults. PROSPERO registration number: CRD42023449190.

COVID-19 in hematopoietic stem cell transplant recipients during three years of the pandemic: a multicenter study in Brazil.

Hematopoietic stem cell transplant (HSCT) recipients are at -increased risk for severe COVID-19. The aim of this study was to evaluate the burden of COVID-19 in a cohort of HSCT recipients. This retrospective study evaluated a cohort of adult hospitalized HSCT recipients diagnosed with COVID-19 in two large hospitals in São Paulo, Brazil post-HSCT, from January 2020 to June 2022. The primary outcome was all-cause mortality. Of 49 cases, 63.2% were male with a median age of 47 years. Allogeneic-HSCT (51.2%) and autologous-HSCT (48.9%) patients were included. The median time from HSCT to COVID-19 diagnosis was 398 days (IQR: 1211-134), with 22 (44.8%) cases occurring within 12 months of transplantation. Most cases occurred during the first year of the pandemic, in non-vaccinated patients (n=35; 71.4%). Most patients developed severe (24.4%) or critical (40.8%) disease; 67.3% received some medication for COVID-19, primarily corticosteroids (53.0%). The probable invasive aspergillosis prevalence was 10.2%. All-cause mortality was 40.8%, 51.4% in non-vaccinated patients and 14.2% in patients who received at least one dose of the vaccine. In the multiple regression analyses, the variables mechanical ventilation (OR: 101.01; 95% CI: 8.205 - 1,242.93; p = 0.003) and chest CT involvement at diagnosis ≥50% (OR: 26.61; 95% CI: 1.06 - 664.26; p = 0.04) remained associated with all-cause mortality. Thus, HSCT recipients with COVID-19 experienced high mortality, highlighting the need for full vaccination and infection prevention measures.

A randomized controlled trial to evaluate the efficacy of metacognitive training for older adults with depression (MCT-Silver) in Portugal: study protocol.

Introduction: Depression is one of the most common psychological disorders in later life. Although psychological interventions are recommended by treatment guidelines, most older adults with depression remain untreated. The aim of this study is to evaluate the efficacy of the Portuguese version of Metacognitive Training for Depression in later life (MCT-Silver). Methods: This is a study protocol of an observer-blind, parallel-group, randomized controlled trial to compare the efficacy of MCT-Silver with a treatment as usual (TAU) control group among older adults (age 65 years and older) with depressive symptoms according to the Montgomery-Asberg Depression Scale. Participants will be tested at three assessment time points (baseline, immediately following the intervention [8 weeks], and 3 months after the intervention). The primary outcome is change in self-rated depression symptoms assessed by the Beck Depression Inventory (BDI-II). Secondary outcomes include clinician-rated depression, self-esteem, dysfunctional beliefs, metacognitive beliefs, ruminations, attitudes toward aging and quality of life. A self-designed subjective appraisal rating scale consisting of 21-items will be used to assess participant acceptance of MCT-Silver. Discussion: MCT-Silver is an innovative intervention, which aims to reduce dysfunctional thoughts as well as depression-related behaviors and coping strategies through the metacognitive perspective. Until now, the training has only been tested in Germany. It is expected that after 8 weeks of treatment and 3 months later, the experimental group will demonstrate significant reductions in depressive symptoms, metacognitive beliefs, dysfunctional attitudes and ruminative responses compared to the TAU group. Moreover, quality of life, self-esteem, and attitudes towards aging will be significantly improved in MCT-Silver compared to the TAU group. Clinical trial registration: ClinicalTrials.gov, NCT05640492.

Depression in older adults during the COVID-19 pandemic: A systematic review.

BACKGROUND: Depression affected 5.7% of people aged 60 years and over prior to the pandemic and has increased by approximately 28%. The aim of this study is to identify and describe factors associated with depressive symptoms, the diagnostic assessment instruments and interventions used to evaluate and treat depression in adults aged 60 years and older since the onset of the COVID-19 pandemic. METHODS: Four electronic databases were systematically searched to identify eligible studies published since the beginning of the COVID-19 pandemic. A total of 832 articles were screened, of which 53 met the inclusion criteria. RESULTS: Factors contributing to depressive symptoms in older adults prior to the pandemic were grouped into the following categories: sociodemographic characteristics (i.e., being female); loneliness and weak social support; limitations in daily functioning, physical activity and neurocognitive impairment; and clinical factors. The following groups of factors directly related to the pandemic were found: stress-related factors and feelings or worries related to the pandemic; information access (e.g., receiving news about COVID-19 through the media); factors directly related to COVID-19 (e.g., having infected acquaintances); and factors related to the measures that were taken to reduce the spread of COVID-19 (e.g., confinement measures). The most frequently used instrument to assess depressive symptoms was the Geriatric Depression Scale Short Form (GDS-SF). Four studies implemented interventions during the pandemic that led to significant reductions in depressive symptoms and feelings of loneliness. CONCLUSIONS: Improved understanding of pandemic-associated risk factors for depression can inform person-cantered care. It is important continued mental healthcare for depression for older adults throughout crises, such as the COVID-19 pandemic. Remote delivery of mental healthcare represents an important alternative during such times. It is crucial to address depression in older adults (which often causes disability), since the pandemic situation has increased depressive symptoms in this population.

Oocyte Retrieval in Asymptomatic Patients Positive for SARS-CoV-2.

Objective: To report two cases of oocyte retrieval performed in asymptomatic SARS-CoV-2-positive patients. Design: Case report. Setting. Outpatient private practice infertility center. Patients. A 28-year-old woman at risk for OHSS who took her trigger injection prior to testing positive for SARS-CoV-2 and a 19-year-old oncofertility patient who tested positive prior to retrieval due to a family exposure. Both patients were asymptomatic. Main Outcome Measures. Cycle outcomes, patient safety, and staff safety. Results: Both patients underwent successful oocyte retrieval procedures without developing symptoms or complications from COVID-19. No staff members that cared for these patients developed symptoms of COVID-19. Conclusion: Worsening fertility outcomes and potential for psychological and financial burdens to the patient must be balanced with risk of perioperative complications in patients testing positive for SARS-CoV-2. As we continue to provide fertility care in a world with COVID-19, appropriate risk mitigation strategies should be implemented to minimize exposure to SARS-CoV-2.

Intersectoral Actions for the Promotion and Prevention of Obesity, Diabetes and Hypertension in Brazilian Cities: A Systematic Review and Meta-Analysis.

This study showed the effectiveness of biomedical interventions in obesity, diabetes and hypertension (NCDs), but innovative and intersectoral elements in the fight against obesity, type 2 diabetes and hypertension were rare. BACKGROUND: Is it possible to find effective and innovative actions to promote health and prevent NCDs in Brazilian municipalities? Can they be replicated? OBJECTIVE: Our objectives were to identify innovative and effective intersectoral actions for promoting and preventing NCDs in Brazilian municipalities. METHODS: This is a systematic review in an exploratory theoretical essay with a qualitative and quantitative approach. It is descriptive and analytical in terms of reporting findings and results. Inclusion and exclusion criteria favored health promotion work. Bias risk assessments was performed using the Cochrane GRADE and bias risk, with meta-analyses using RevMan and Iramuteq. RESULTS: Meta-analysis of biometric markers resulted in -4.46 [95% IC; -5.42, -3.49], p = 0.00001, indicating a reduction in NCD risk rates. The textual meta-analysis revealed P(r) ≈ 83% (Reinert), meaning low connectivity between the 'halos'. CONCLUSIONS: There is evidence of the effectiveness in interventions, but innovative and intersectoral elements to combat and prevent NCDs were barely seen. While evidence of intervention effectiveness was observed, innovative and intersectoral elements to combat and prevent NCDs were barely noticed.

Depression in older adults during the COVID-19 pandemic: a systematic review protocol.

INTRODUCTION: Depression is a common mental disorder and is a major cause of years lived with disability. The COVID-19 pandemic has caused an increase in the prevalence of depression worldwide. Our aim is to identify and synthesise the determinants of depression, the diagnostic assessment tools used to evaluate depression, and the interventions carried out since the beginning of the COVID-19 pandemic in the population aged 60 and older. METHODS AND ANALYSIS: A systematic review of the literature will be conducted. The following databases will be searched: CINAHL Plus with Full Text, MedicLatina, MEDLINE with Full Text, and Psychology and Behavioural Sciences Collection. The search strategy will include the following Medical Subject Headings or similar terms: "Depression", "Depressive Disorder", "Depressive Symptoms", "Older Adults", "Aging", "Elderly", Pandemic" and "COVID-19". Two independent reviewers will ascertain whether the resulting articles meet inclusion and exclusion criteria, and perform the analysis of data quality. Disagreements will be resolved by a third reviewer. All studies reported between December 2019 and March 2022 meeting the following criteria will be included: studies in adults aged 60 and over, and articles written in English, Portuguese, Spanish or German. Information on determinants of depression, assessment instruments used to assess depressive symptoms and/or interventions to decrease depression are reported. Studies will not be excluded based on geographical area study context (eg, community, culture or specific environment). All studies related to diagnostic assessment, care planning and/or intervention strategies specifically for older adults with depression will be included. ETHICS AND DISSEMINATION: As only secondary data will be analysed, no ethical approval is required for this study. This scientific article is a systematic review protocol for which data have not yet been extracted or analysed. The results will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42022299775.

Developing a referral system for fertility preservation among patients with newly diagnosed cancer.

The goal of this project was to develop a referral system to increase the likelihood that patients of childbearing age with newly diagnosed cancer receive timely information about fertility, and reduce the burden oncologists may feel when discussing and exploring fertility preservation options with their patients. The group developed and examined the effectiveness of a fertility preservation referral system through pilot-testing a developed patient education brochure. During the 12-month pilot-testing period, 776 patients of childbearing age (< 40 years) were seen at H. Lee Moffitt Cancer Center and 349 brochures were taken. The reproductive endocrinologist/infertility clinic experienced a 9-fold increase in the number of calls received during the 12-month study period, with 122 calls received compared with 13 the prior year. The large increase in calls illuminates the gap in patient interest and referral, and shows an effective method to transmit this information. Improving the communication of time-sensitive information about fertility and preservation options to patients with cancer is associated with an increased likelihood of improving quality of life, reducing patient distress, and increasing use of ancillary fertility-related health services. Through referring and providing patient information, this referral system allows oncologists to fulfill their obligation and make informed decisions about fertility preservation, thereby improving the full cancer care continuum.

Late recurrence of Burkitt's lymphoma in the jaw: numb chin syndrome as the only symptom.

The Numb Chin Syndrome (NCS) is defined as facial and oral numbness restricted to the mental nerve's distribution involving the lower lip, skin of the chin, or gingiva of the lower anterior teeth. Hypoesthesia can occur unilaterally or bilaterally. Although this syndrome is rare, its importance is related to the fact that it represents the clinical manifestations of malignant diseases. Breast cancer and non-Hodgkin lymphoma are the most common cause of NCS. The patient, a 58-year-old woman, treated for a Burkitt Lymphoma (BL) nine years ago, described a two-week history of change in sensitivity and pain in the chin region, without relief with the use of analgesics. She had no headache, speech disturbance, dysphagia, visual disturbance, or other neurological symptoms. No surgical intervention has been performed recently. The intraoral examination revealed a healthy oral mucosa and a small area adjacent to the right mental nerve region that was uncomfortable to palpation. No changes were found in the bone trabeculae at cone-beam computed tomography. The contrasted magnetic resonance features made it possible to identify a change in the mandibular body extending to the entire right side, coinciding with the patient's complaint, indicating a probable mandibular medullary invasion. The patient was submitted to a biopsy to rule out a possible recurrence of BL. The microscopic findings were consistent with the diagnosis of BL. The present report described a very unusual presentation of late recurrent BL nine years after the first treatment, which manifested as an NCS.

Are early human chorionic gonadotropin levels after methotrexate therapy a predictor of response in ectopic pregnancy?

OBJECTIVE: The purpose of this study was to evaluate beta-human chorionic gonadotropin (beta-hCG) levels between days 0 and 4 as a predictor of methotrexate therapy success for ectopic pregnancy. STUDY DESIGN: We conducted a retrospective study that evaluated posttreatment beta-hCG levels of 30 patients with ectopic pregnancy who had been treated with single-dose methotrexate therapy. RESULTS: beta-hCG levels decreased between days 0 and 4 in 40.0% of cases, and 100% of these cases had treatment success. beta-hCG levels increased in 60.0% of cases, and 61.8% of these cases had treatment success. In patients with increasing beta-hCG levels on day 4, we calculated the beta-hCG "difference variable" (beta-hCG level at day 4 minus day 0). The median beta-hCG difference variable between cases of treatment success and failure were statistically significant (P = .035). CONCLUSION: beta-hCG level changes between days 0 and 4 after methotrexate therapy have clinical significance and predictive value. Decreasing beta-hCG levels is highly predictive of treatment success. The beta-hCG difference variable is a reliable predictor of success in cases with rising beta-hCG levels after methotrexate therapy.

Expression profile of male germ cell-associated genes in mouse embryonic stem cell cultures treated with all-trans retinoic acid and testosterone.

Cells that morphologically and functionally resemble male germ cells can be spontaneously derived from ES cells. However, this process is inefficient and unpredictable suggesting that the expression pattern of male germ cell associated genes during spontaneous ES cell differentiation does not mimic the in vivo profiles of the genes. Thus, in the present study, the temporal profile of genes expressed at different stages of male germ cell development was examined in differentiating ES cells. The effect of all-trans retinoic acid (RA) which is a known inducer of primordial germ cell (PGC) proliferation/survival in vitro and testosterone which is required for spermatogenesis in vivo on the expression of these genes was also determined. Each of the 12 genes analyzed exhibited one of four temporal expression patterns in untreated differentiating ES cells: progressively decreased (Dppa3, Sycp3, Msy2), initially low and then increased (Stra8, Sycp1, Dazl, Act, Prm1), initially decreased and then increased (Piwil2, Tex14), or relatively unchanged (Akap3, Odf2). RA-treated cells exhibited increased expression of Stra8, Dazl, Act, and Prm1 and suppressed expression of Dppa3 compared to untreated controls. Furthermore, testosterone increased expression of Stra8 while the combination of RA and testosterone synergistically increased expression of Act. Our findings establish a comprehensive profile of male germ cell gene expression during spontaneous differentiation of murine ES cells and describe the capacity of RA and testosterone to modulate the expression of these genes. Furthermore, these data represent an important first step in designing a plausible directed differentiation protocol for male germ cells.

The promoter of the oocyte-specific gene, Gdf9, is active in population of cultured mouse embryonic stem cells with an oocyte-like phenotype.

The study of germ cell-specific gene regulation in vitro is challenging. Here we report that the promoter of the oocyte-specific gene, Gdf9, is active in a population of cultured murine embryonic stem cells (ES) which have a phenotype resembling oocytes. The promoter region of the murine Gdf9 coupled to enhanced green fluorescent protein (eGFP) was stably transfected into XX mouse ES cells. eGFP was expressed only in oocytes of chimeric mice generated from the transfected XX ES cells. The transfected ES cells were examined when cultured on feeder layers or as embryoid bodies. Large eGFP-positive cells, surrounded by a structure resembling a zona pellucida appeared transiently in cultures of the ES cells on feeder layers. Surprisingly, they were detectable on days 1 and 2 of culture but virtually absent on day 3. Addition of leukemia inhibitory factor (LIF) to the media significantly increased the number of eGFP-positive cels resembling oocytes. Quantitative-time PCR demonstrated a parallel increase in Gdf9 and Zp3 mRNA with changes in the abundance of eGFP-positive cells. In embryoid body cultures, eGFP-positive cells appeared transiently and then re-appeared in regional clusters after 30-45 days of culture. These findings demonstrate that a population of cultured murine ES cells contain the transcriptional machinery to drive expression of an oocyte-specific gene, and that those cells phenotypically resemble oocytes.

COVID-19 in hematopoietic stem cell transplant recipients during three years of the pandemic: a multicenter study in Brazil

ABSTRACT Hematopoietic stem cell transplant (HSCT) recipients are at -increased risk for severe COVID-19. The aim of this study was to evaluate the burden of COVID-19 in a cohort of HSCT recipients. This retrospective study evaluated a cohort of adult hospitalized HSCT recipients diagnosed with COVID-19 in two large hospitals in São Paulo, Brazil post-HSCT, from January 2020 to June 2022. The primary outcome was all-cause mortality. Of 49 cases, 63.2% were male with a median age of 47 years. Allogeneic-HSCT (51.2%) and autologous-HSCT (48.9%) patients were included. The median time from HSCT to COVID-19 diagnosis was 398 days (IQR: 1211-134), with 22 (44.8%) cases occurring within 12 months of transplantation. Most cases occurred during the first year of the pandemic, in non-vaccinated patients (n=35; 71.4%). Most patients developed severe (24.4%) or critical (40.8%) disease; 67.3% received some medication for COVID-19, primarily corticosteroids (53.0%). The probable invasive aspergillosis prevalence was 10.2%. All-cause mortality was 40.8%, 51.4% in non-vaccinated patients and 14.2% in patients who received at least one dose of the vaccine. In the multiple regression analyses, the variables mechanical ventilation (OR: 101.01; 95% CI: 8.205 - 1,242.93; p = 0.003) and chest CT involvement at diagnosis ≥50% (OR: 26.61; 95% CI: 1.06 - 664.26; p = 0.04) remained associated with all-cause mortality. Thus, HSCT recipients with COVID-19 experienced high mortality, highlighting the need for full vaccination and infection prevention measures.

Update on the approach to smoking in patients with respiratory diseases.

Smoking is the leading cause of respiratory disease (RD). The harmful effects of smoking on the respiratory system begin in utero and influence immune responses throughout childhood and adult life. In comparison with "healthy" smokers, smokers with RD have peculiarities that can impede smoking cessation, such as a higher level of nicotine dependence; nicotine withdrawal; higher levels of exhaled carbon monoxide; low motivation and low self-efficacy; greater concern about weight gain; and a high prevalence of anxiety and depression. In addition, they require more intensive, prolonged treatment. It is always necessary to educate such individuals about the fact that quitting smoking is the only measure that will reduce the progression of RD and improve their quality of life, regardless of the duration and severity of the disease. Physicians should always offer smoking cessation treatment. Outpatient or inpatient smoking cessation treatment should be multidisciplinary, based on behavioral interventions and pharmacotherapy. It will thus be more effective and cost-effective, doubling the chances of success.

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality.

Breast cancer remains a leading cause of morbidity and mortality worldwide yet methods for early detection remain elusive. We describe the discovery and validation of biochemical signatures measured by mass spectrometry, performed upon blood samples from patients and controls that accurately identify (>95%) the presence of clinical breast cancer. Targeted quantitative MS/MS conducted upon 1225 individuals, including patients with breast and other cancers, normal controls as well as individuals with a variety of metabolic disorders provide a biochemical phenotype that accurately identifies the presence of breast cancer and predicts response and survival following the administration of neoadjuvant chemotherapy. The metabolic changes identified are consistent with inborn-like errors of metabolism and define a continuum from normal controls to elevated risk to invasive breast cancer. Similar results were observed in other adenocarcinomas but were not found in squamous cell cancers or hematologic neoplasms. The findings describe a new early detection platform for breast cancer and support a role for pre-existing, inborn-like errors of metabolism in the process of breast carcinogenesis that may also extend to other glandular malignancies. Statement of Significance: Findings provide a powerful tool for early detection and the assessment of prognosis in breast cancer and define a novel concept of breast carcinogenesis that characterizes malignant transformation as the clinical manifestation of underlying metabolic insufficiencies.

IVTH BRAZILIAN CONSENSUS CONFERENCE ON HELICOBACTER PYLORI INFECTION.

Significant progress has been obtained since the III Brazilian Consensus Conference on H. pylori infection held in 2012, in Bento Gonçalves, Brazil, and justify a fourth meeting to establish updated guidelines on the current management of H. pylori infection. Therefore, the Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM), association linked to Brazilian Federation of Gastroenterology (FBG) held its fourth meeting again in Bento Gonçalves, RS, Brazil, on August 25-27, 2017. Twenty-six delegates, including gastroenterologists, endoscopists, and pathologists from the five regions of Brazil as well as one international guest from the United States, participated in the meeting. The participants were invited based on their knowledge and contribution to the study of H. pylori infection. The meeting sought to review different aspects of treatment for infection; establish a correlation between infection, dyspepsia, intestinal microbiota changes, and other disorders with a special emphasis on gastric cancer; and reassess the epidemiological and diagnostic aspects of H. pylori infection. Participants were allocated into four groups as follows: 1) Epidemiology and Diagnosis, 2) Dyspepsia, intestinal microbiota and other afections, 3) Gastric Cancer, and, 4) Treatment. Before the consensus meeting, participants received a topic to be discussed and prepared a document containing a recent literature review and statements that should be discussed and eventually modified during the face-to-face meeting. All statements were evaluated in two rounds of voting. Initially, each participant discussed the document and statements with his group for possible modifications and voting. Subsequently, during a second voting in a plenary session in the presence of all participants, the statements were voted upon and eventually modified. The participants could vote using five alternatives: 1) strongly agree; 2) partially agree; 3) undecided; 4) disagree; and 5) strongly disagree. The adopted consensus index was that 80% of the participants responded that they strongly or partially agreed with each statement. The recommendations reported are intended to provide the most current and relevant evidences to management of H. pylori infection in adult population in Brazil.