Study of late toxicity biomarkers of locally advanced head and neck cancer patients treated with radiotherapy plus cisplatin or cetuximab points to the relevance of skin macrophages (TOX-TTCC-2015-01).

PURPOSE: Radiotherapy (RT) with concomitant cisplatin (CRT) or cetuximab (ERT) are accepted treatment options for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Long-term adverse events (AEs) have a vast impact on patients' quality of life. This study explored tissue biomarkers which could help predict late toxicity. METHODS/PATIENTS: Single-institution prospective study including patients aged ≥ 18 with histologically confirmed newly diagnosed LA-SCCHN treated with RT and either concomitant cisplatin q3w or weekly cetuximab, according to institutional protocols. All patients underwent pre- and post-treatment skin biopsies of neck regions included in the clinical target volume. Angiogenesis, macrophages, and extracellular matrix (ECM) markers were evaluated by immunohistochemistry (IHC). RESULTS: From April 15, 2016, to December 11, 2017; 31 patients were evaluated [CRT = 12 (38.7%) and ERT = 19 (61.3%)]. 27 patients (87%) had received induction chemotherapy. All patients finished RT as planned. IHC expression of vasculature (CD34) and collagen (Masson's Trichrome) did not differ significantly between and within CRT and ERT arms. Conversely, an increased CD68 and CD163 macrophage infiltration expression was observed after treatment, without significant impact of treatment modality. Patients with higher late toxicity showed lower expression of macrophage markers in pre-treatment samples compared with those with lower late toxicity, with statistically significant differences for CD68. CONCLUSIONS: Angiogenesis and ECM biomarkers did not differ significantly between CRT and ERT. Macrophage markers increased after both treatments and deserve further investigation as predictors of late toxicity in LA-SCCHN patients. [Protocol code: TOX-TTCC-2015-01/Spanish registry of clinical studies (REec): 2015-003012-21/Date of registration: 27/01/2016].

Integrative Taxonomy Reveals Hidden Diversity in the Aloina catillum Complex (Pottiaceae, Bryophyta).

Aloina catillum is a variable moss typical of xerophytic environments in the Neotropics, characterized against other closely allied Aloina species with well-differentiated leaf border by its setae twisted to the left throughout. In order to clarify its variability and its relationships with the allied species with differentiated leaf border A. brevirostris, A. obliquifolia, and A. rigida, we performed an integrative study including sequence data from four markers (nuclear ITS, plastid atpB-rbcL, trnG, trnL-F), morphometry, and species assembling by automatic partitioning (ASAP) algorithm. Our data suggest that A. catillum consists of at least three species: A. calceolifolia (an earlier name for A. catillum), and two species described here as a new, A. bracteata sp. nov. and A. limbata sp. nov. This latter species includes the specimens previously identified as A. obliquifolia from South America. Additionally, some morphological and molecular variability was also detected in A. limbata, but was not consistent enough to be recognized taxonomically. The study supports the presence of A. brevirostris in the Neotropics and A. rigida is tentatively excluded from South America. Full descriptions of the A. catillum s.l. species and a diagnostic key to this complex in South America are provided.

Ovarian cancer relies on the PDGFRß-fibronectin axis for tumorsphere formation and metastatic spread.

High-grade serous ovarian cancer (HGSOC) is the deadliest gynecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In this process, detached cells from the primary tumor aggregate as tumorspheres and promote the accumulation of peritoneal ascites. This represents an early event in HGSOC development and is indicative of poor prognosis. In this study, based on tumorspheres isolated from ascitic liquid samples from HGSOC patients, ovarian cancer spheroid 3D cultures, and in vivo models, we describe a key signal for tumorsphere formation in HGSOC. We report that platelet-derived growth factor receptor beta (PDGFRß) is essential for fibronectin-mediated cell clustering of ovarian cancer cells into tumorspheres. This effect is mediated by the kinase NUAK family SNF1-like kinase 1 (NUAK1) and blocked by PDGFRß pharmacological or genetic inhibition. In the absence of PDGFRß, ovarian cancer cells can be provided with fibronectin by cancer-associated fibroblasts to generate chimeric spheroids. This work provides new insights that uncover potential targets to prevent peritoneal dissemination, the main cause of advanced disease in HGSOC patients.

Effects of Non-Invasive Neuromodulation of the Vagus Nerve for the Management of Cluster Headache: A Systematic Review.

BACKGROUND: Cluster headache (CH) is a type of headache that has a global prevalence of 0.5-3/1000 people, provokes severe, strictly unilateral pain through the first branch of the trigeminal nerve, and is associated with observable autonomous responses. CH provokes intense pain and decreases quality of life. OBJECTIVE: In this study, we aimed to carry out a systematic review of the effectiveness of non-invasive neuromodulation of the vagus nerve in patients with cluster headaches, which was registered on PROSPERO No. CRD42021265126. METHODS: Six databases were used from their date of inception to February 2023 to obtain studies with the group intervention of non-invasive neuromodulation of the vagus nerve for cluster headache, with outcomes based on pain attacks, duration, and disabilities. Data on the subjects, group intervention, main outcomes, and results were collected by two authors. RESULTS: The search provided 1003 articles, with three clinical trials being eligible for inclusion in the review. The methodological quality scores ranged from 6 to 8 points (mean: 7.3, SD: 0.8) out of a maximum of 10 points. The post-treatment results showed some positive effects using n-VNS as a treatment for cluster headache, more specifically regarding cervical neuromodulation of the vagus nerve. CONCLUSIONS: The systematic review found moderate-to-high-quality evidence supporting that n-VNS and cervical n-VNS may have some positive effects at the end of the treatment being effective to relieve the frequency and intensity of cluster headaches. The poor quantity of studies available and the lack of homogeneity in the study protocols did not allow the pooling of data for a meta-analysis.

Management of auricular transcutaneous neuromodulation and electro-acupuncture of the vagus nerve for chronic migraine: a systematic review.

Background: Migraine is a type of primary headache that is accompanied by symptoms such as nausea, vomiting, or sensitivity to light and sound. Objective: The aim of this study was to conduct a systematic review on the effectiveness of non-invasive neuromodulation, auricular transcutaneous vagus nerve stimulation (at-VNS), and electro-ear acupuncture of the vagus nerve in patients with migraine headaches. Methods: Six databases were searched from inception to 15 June 2022 for clinical trials, in which at least one group received any form of non-invasive neuromodulation of the vagus nerve for managing migraine with outcomes collected on pain intensity and related disability. Data, including participants, interventions, blinding strategy, outcomes, and results, were extracted by two reviewers. The methodological quality was assessed with the PEDro scale, ROB, and Oxford scale. Results: The search identified 1,117 publications with nine trials eligible for inclusion in the review. The methodological quality scores ranged from 6 to 8 (mean: 7.3, SD: 0.8) points. Low-quality evidence suggests some positive clinical effects for the treatment of chronic migraine with 1 Hz with at-VNS and ear-electro-acupuncture compared with the control group at post-treatment. Some of the studies provided evidence of the relationship between chronic migraine and a possible positive effect as a treatment with at-VNS and the neurophysiological effects using fMRI. Six of the studies provided evidence using fMRI of the relationship between chronic migraine and a possible positive effect as a treatment with at-VNS and the neurophysiological effects. Regarding all included studies, the level of evidence with the Oxford scale was level 1 (11.17%), six studies were graded as level 2 (66.66%), and two studies were graded as level 3 (22.2%). With the PEDro score, five studies got a low methodological score < 5 and only four got a score superior to 5, being highly methodological quality studies. For ROB, most of the studies were high risk and only a few of them received a low risk of bias. The pain intensity, migraine attacks, frequency, and duration were measured by three studies with positive results at post-treatment. And only 7% reported adverse events using at-VNS. All studies reported results at a post-treatment period in their respective main outcomes. And all studies with fMRI provided strong evidence of the relationship between the Locus Coeruleus, Frontal Cortex, and other superior brain areas with the auricular branch of the Vagus nerve with at-VNS. Conclusion: Some positive effects regarding the effect of non-invasive neuromodulation, auricular transcutaneous vagus nerve stimulation (at-VNS), and electro-ear acupuncture of the vagus nerve on migraine is reported in the current literature, but there are not enough data to obtain strong conclusions. Systematic review registration: This systematic review was registered in the PROSPERO database (registration number: CRD42021265126).

Effects of Non-Invasive Neuromodulation of the Vagus Nerve for Management of Tinnitus: A Systematic Review with Meta-Analysis.

BACKGROUND: Tinnitus is the perception of sound in the absence of actual external stimuli. Other associated symptoms include frustration, annoyance, anxiety, depression, stress, cognitive dysfunction, insomnia, or emotional exhaustion. OBJECTIVE: In this study, we aimed to conduct a systematic review and meta-analysis on the effectiveness of the non-invasive neuromodulation of the vagus nerve in patients with tinnitus. METHODS: Six databases were searched from their date of inception to 15 June 2022 to identify clinical trials in which at least one group received any form of non-invasive neuromodulation of the vagus nerve for tinnitus management, with outcomes based on annoyance and related disability. Data on participants, interventions, blinding strategies, assessment outcomes, and results were extracted by two reviewers. RESULTS: The search identified 183 articles with five clinical trials eligible for inclusion in the review and four for the meta-analysis. The methodological quality scores ranged from 6 to 8 (mean: 7.3, SD: 0.8) points. The meta-analysis identified a significant positive effect on THI post-treatment for unilateral auricular stimulation (hg = 0.69, 95% CI 0.06, 1.32) or transcutaneous nerve stimulation (hg = 0.51, 95% CI 0.1, 0.9) compared with a comparative group. No effect on loudness intensity was observed. CONCLUSION: The results of the meta-analysis suggest that the application of the non-invasive neuromodulation of the vagus nerve has a positive effect post-treatment in terms of related disability in patients with tinnitus, although its clinical relevance is low. No firm conclusions about the effect of the non-invasive neuromodulation of the vagus nerve on tinnitus are available based on the current literature.

Morphological Changes of the Suboccipital Musculature in Women with Myofascial Temporomandibular Pain: A Case-Control Study.

Temporomandibular disorder (TMD) is an umbrella term including pain problems involving the cranio-cervical region. It has been suggested that patients with TMD also exhibit cervical spine disturbances. Evidence suggests the presence of morphological changes in the deep cervical muscles in individuals with headaches. The objective of this study was to compare the morphology of the suboccipital muscles between women with TMD and healthy controls. An observational, cross-sectional case-control study was conducted. An ultrasound examination of the suboccipital musculature (rectus capitis posterior minor, rectus capitis posterior major, oblique capitis superior, oblique capitis inferior) was conducted in 20 women with myofascial TMD and 20 matched controls. The cross-sectional area (CSA), perimeter, depth, width, and length of each muscle were calculated by a blinded assessor. The results revealed that women with myofascial TMD pain exhibited bilaterally reduced thickness, CSA, and perimeter in all the suboccipital muscles when compared with healthy women. The width and depth of the suboccipital musculature were similar between women with myofascial TMD and pain-free controls. This study found morphological changes in the suboccipital muscles in women with myofascial TMD pain. These changes can be related to muscle atrophy and are similar to those previously found in women with headaches. Future studies are required to investigate the clinical relevance of these findings by determining if the specific treatment of these muscles could help clinically patients with myofascial TMD.

Cabozantinib sensitizes microsatellite stable colorectal cancer to immune checkpoint blockade by immune modulation in human immune system mouse models.

Immune checkpoint inhibitors have been found to be effective in metastatic MSI-high colorectal cancers (CRC), however, have no efficacy in microsatellite stable (MSS) cancers, which comprise the majority of mCRC cases. Cabozantinib is a small molecule multi-tyrosine kinase inhibitor that is FDA approved in advanced renal cell, medullary thyroid, and hepatocellular carcinoma. Using Human Immune System (HIS) mice, we tested the ability of cabozantinib to prime MSS-CRC tumors to enhance the potency of immune checkpoint inhibitor nivolumab. In four independent experiments, we implanted distinct MSS-CRC patient-derived xenografts (PDXs) into the flanks of humanized BALB/c-Rag2nullIl2rγnullSirpαNOD (BRGS) mice that had been engrafted with human hematopoietic stem cells at birth. For each PDX, HIS-mice cohorts were treated with vehicle, nivolumab, cabozantinib, or the combination. In three out of the four models, the combination had a lower tumor growth rate compared to vehicle or nivolumab-treated groups. Furthermore, interrogation of the HIS in immune organs and tumors by flow cytometry revealed increased Granzyme B+, TNFα+ and IFNγ+ CD4+ T cells among the human tumor infiltrating leukocytes (TIL) that correlated with reduced tumor growth in the combination-treated HIS-mice. Notably, slower growth correlated with increased expression of the CD4+ T cell ligand, HLA-DR, on the tumor cells themselves. Finally, the cabozantinib/nivolumab combination was tested in comparison to cobimetinib/atezolizumab. Although both combinations showed tumor growth inhibition, cabozantinib/nivolumab had enhanced cytotoxic IFNγ and TNFα+ T cells. This pre-clinical in vivo data warrants testing the combination in clinical trials for patients with MSS-CRC.

Paclitaxel Plus Cetuximab as Induction Chemotherapy for Patients With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma Unfit for Cisplatin-Based Chemotherapy.

Objectives: Induction chemotherapy (ICT) followed by definitive treatment is an accepted non-surgical approach for locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, ICT remains a challenge for cisplatin-unfit patients. We evaluated paclitaxel and cetuximab (P-C) as ICT in a cohort of LA-HNSCC patients unfit for cisplatin. Materials and Methods: This is a retrospective analysis of patients with newly diagnosed LA-HNSCC considered unfit for cisplatin-based chemotherapy (age >70 and/or ECOG≥2 and/or comorbidities) treated with weekly P-C followed by definitive radiotherapy and cetuximab (RT-C) between 2010 and 2017. Toxicity and objective response rate (ORR) to ICT and RT-C were collected. Median overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cox regression analysis was performed to determine baseline predictors of OS and PFS. Results: A total of 57 patients were included. Grade 3-4 toxicity rate to ICT was 54.4%, and there was a death deemed treatment-related (G5). P-C achieved an ORR of 66.7%, including 12.3% of complete responses (CR). After P-C, 45 patients (78.9%) continued with concomitant RT-C. Twenty-six patients (45.6%) achieved a CR after definitive treatment. With a median follow-up of 21.7 months (range 1.2-94.6), median OS and PFS were 22.9 months and 10.7 months, respectively. The estimated 2-year OS and PFS rates were 48.9% and 33.7%, respectively. Disease stage had a negative impact on OS (stage IVb vs. III-IVa: HR = 2.55 [1.08-6.04], p = 0.03), with a trend towards worse PFS (HR = 1.92 [0.91-4.05], p = 0.09). Primary tumor in the larynx was associated with improved PFS but not OS (HR = 0.45 [0.22-0.92], p = 0.03, and HR = 0.69 [0.32-1.54], p = 0.37, respectively). Conclusion: P-C was a well-tolerated and active ICT regimen in this cohort of LA-HNSCC patients unfit for cisplatin-based chemotherapy. P-C might represent a valid ICT option for unfit patients and may aid patient selection for definitive treatment.

Facts and Hopes in Immunotherapy of Endometrial Cancer.

Immunotherapy with checkpoint inhibitors has changed the paradigm of treatment for many tumors, and endometrial carcinoma is not an exception. Approved treatment options are pembrolizumab or dostarlimab for mismatch repair deficient tumors, pembrolizumab for tumors with high mutational load, and, more recently, pembrolizumab/lenvatinib for all patients with endometrial cancer. Endometrial cancer is a heterogeneous disease with distinct molecular subtypes and different prognoses. Differences between molecular subgroups regarding antigenicity and immunogenicity should be relevant to develop more tailored immunotherapeutic approaches. In this review, we aim to summarize and discuss the current evidence-Facts, and future opportunities-Hopes-of immunotherapy for endometrial cancer, focusing on relevant molecular and tumor microenvironment features of The Cancer Genome Atlas endometrial cancer subtypes.

Circumscription and Phylogenetic Position of Two Propagulose Species of Syntrichia (Pottiaceae, Bryophyta) Reveals Minor Realignments within the Tribe Syntricheae.

In the course of a worldwide revision of the genus Syntrichia, we identified problems in the circumscription of some species of the genus as well as among some allied genera grouped in the tribe Syntricheae. This is the case for the two propagulose Syntrichia amphidiacea and S. gemmascens, closely related to Streptopogon. We analyzed phylogenetic relationships between these species, based on nuclear (ITS) and two plastid (trnL-F and trnG) markers and morphological features. Species delimitation using molecular data was consistent with our preliminary morphological inference. Phylogenetic analyses were performed using maximum likelihood and Bayesian inference methods. Our results placed Syntrichia amphidiacea in the Streptopogon clade. Syntrichia gemmascens is also included in Streptopogon in spite of the discrepancy of the ITS and plastid relationships, which could be evidence of an exchange of genetic material between species in various lineages in the Pottioideae. Streptopogon is maintained as a separate genus on the basis of morphology characters, and we consider the differentiation of laminal papillae and the presence of a stem central strand as new characters in the genus. We accept Sagenotortula as distinct genus sister to Syntrichia. We consider the lack of costal dorsal epidermis and the differentiation of a crescent-shaped costal dorsal stereid band as distinctive generic characters in Syntrichia. Additionally, we include Syntrichia percarnosa as a new synonym for S. breviseta. Three names are lectotypified.

Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors.

Reversing the immunosuppressive nature of the tumor microenvironment is critical for the successful treatment of cancers with immunotherapy drugs. Murine cancer models are extremely limited in their diversity and suffer from poor translation to the clinic. To serve as a more physiological preclinical model for immunotherapy studies, this protocol has been developed to evaluate the treatment of human tumors in a mouse reconstituted with a human immune system. This unique protocol demonstrates the development of human immune system (HIS, "humanized") mice, followed by implantation of a human tumor, either a cell-line derived xenograft (CDX) or a patient derived xenograft (PDX). HIS mice are generated by injecting CD34+ human hematopoietic stem cells isolated from umbilical cord blood into neonatal BRGS (BALB/c Rag2-/- IL2RγC-/- NODSIRPα) highly immunodeficient mice that are also capable of accepting a xenogeneic tumor. The importance of the kinetics and characteristics of the human immune system development and tumor implantation is emphasized. Finally, an in-depth evaluation of the tumor microenvironment using flow cytometry is described. In numerous studies using this protocol, it was found that the tumor microenvironment of individual tumors is recapitulated in HIS-PDX mice; "hot" tumors exhibit large immune infiltration while "cold" tumors do not. This model serves as a testing ground for combination immunotherapies for a wide range of human tumors and represents an important tool in the quest for personalized medicine.

Testing Cancer Immunotherapy in a Human Immune System Mouse Model: Correlating Treatment Responses to Human Chimerism, Therapeutic Variables and Immune Cell Phenotypes.

Over the past decade, immunotherapies have revolutionized the treatment of cancer. Although the success of immunotherapy is remarkable, it is still limited to a subset of patients. More than 1500 clinical trials are currently ongoing with a goal of improving the efficacy of immunotherapy through co-administration of other agents. Preclinical, small-animal models are strongly desired to increase the pace of scientific discovery, while reducing the cost of combination drug testing in humans. Human immune system (HIS) mice are highly immune-deficient mouse recipients rtpeconstituted with human hematopoietic stem cells. These HIS-mice are capable of growing human tumor cell lines and patient-derived tumor xenografts. This model allows rapid testing of multiple, immune-related therapeutics for tumors originating from unique clinical samples. Using a cord blood-derived HIS-BALB/c-Rag2nullIl2rγnullSIRPαNOD (BRGS) mouse model, we summarize our experiments testing immune checkpoint blockade combinations in these mice bearing a variety of human tumors, including breast, colorectal, pancreatic, lung, adrenocortical, melanoma and hematological malignancies. We present in-depth characterization of the kinetics and subsets of the HIS in lymph and non-lymph organs and relate these to protocol development and immune-related treatment responses. Furthermore, we compare the phenotype of the HIS in lymph tissues and tumors. We show that the immunotype and amount of tumor infiltrating leukocytes are widely-variable and that this phenotype is tumor-dependent in the HIS-BRGS model. We further present flow cytometric analyses of immune cell subsets, activation state, cytokine production and inhibitory receptor expression in peripheral lymph organs and tumors. We show that responding tumors bear human infiltrating T cells with a more inflammatory signature compared to non-responding tumors, similar to reports of "responding" patients in human immunotherapy clinical trials. Collectively these data support the use of HIS mice as a preclinical model to test combination immunotherapies for human cancers, if careful attention is taken to both protocol details and data analysis.

Cadaveric and in vivo validation of needle placement in the medial pterygoid muscle.

BACKGROUND: Evidence suggests that medial pterygoid muscle plays an important role in temporomandibular pain. Therapeutic approaches targeting this muscle are needed. OBJECTIVE: To determine if a solid needle accurately penetrates the medial pterygoid muscle during the application of dry needling. DESIGN: A cadaveric and human descriptive study. METHODS: Needling insertion of the medial pterygoid was conducted in 5 fresh cadaver and 5 subjects with temporomandibular pain. Needling insertion was performed using a 40 mm needle inserted at the inferior angle of the mandibular bone. The needle was advanced from an inferior to superior direction into the medial pterygoid to a maximum depth of 30 mm. In cadavers, medial pterygoid placement was assessed by observation after resecting the superficial overlying tissues. In patients, medial pterygoid placement was assessed by self-reported pain referral during insertion. RESULTS: Accurate needle penetration of the medial pterygoid was observed in all fresh cadavers and pain referral was reported by 4/5 patients during needling insertion. CONCLUSION: Results from both cadavers and patients support the assertion that needling of the medial pterygoid can be accurately conducted.

Determinants and Functions of CAFs Secretome During Cancer Progression and Therapy.

Multiple lines of evidence are indicating that cancer development and malignant progression are not exclusively epithelial cancer cell-autonomous processes but may also depend on crosstalk with the surrounding tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are abundantly represented in the TME and are continuously interacting with cancer cells. CAFs are regulating key mechanisms during progression to metastasis and response to treatment by enhancing cancer cells survival and aggressiveness. The latest advances in CAFs biology are pointing to CAFs-secreted factors as druggable targets and companion tools for cancer diagnosis and prognosis. Especially, extensive research conducted in the recent years has underscored the potential of several cytokines as actionable biomarkers that are currently evaluated in the clinical setting. In this review, we explore the current understanding of CAFs secretome determinants and functions to discuss their clinical implication in oncology.

Cadaveric and ultrasonographic validation of needling placement in the obliquus capitis inferior muscle.

BACKGROUND: Evidence suggests that suboccipital musculature plays an important role in headache. Proper therapeutic approaches targeting this muscle are needed. OBJECTIVE: Our aim was to determine with fresh cadavers and ultrasound imaging if a solid needle is able to properly penetrate the obliquus capitis inferior muscle during the application of dry needling. DESIGN: A cadaveric and human descriptive study. METHODS: Needling insertion and ultrasound imaging of the obliquus capitis inferior muscle was conducted on 10 pain-free healthy subjects and 5 fresh cadavers. Needling insertion was performed using a 40 mm needle inserted midway between the spinous process of C2 and transverse process of C1. The needle was advanced from a posterior to anterior direction into the obliquus capitis inferior muscle with an inferior-lateral angle to reach the lamina of C2. For the cadaveric study, the obliquus capitis inferior placement was verified by resecting the superficial upper trapezius, splenius capitis, and semispinalis capitis muscles. For ultrasographic study, a linear transducer was aligned with the long axis of the obliquus capitis inferior muscle after needle insertion. RESULTS: Both the cadaveric and ultrasonic studies showed that the needle penetrated the obliquus capitis inferior muscle during its insertion and that the tip of the needle rested against C2 laminae, thereby reaching the targeted muscle. CONCLUSION: This anatomical and ultrasound imaging study supports the assertion that needling insertion of the obliquus capitis inferior muscle can be properly conducted by an experienced clinician.

Dengue durante el embarazo, menor incidencia de trombocitopenia que en la población general / Dengue during pregnancy, less incidence of thrombocytopenia than in general population

RESUMEN Objetivo El dengue es una enfermedad viral generalmente autolimitada, que en México se considera un problema de salud pública. Puede acompañarse de alteraciones de laboratorio como neutropenia, linfopenia y trombocitopenia. El objetivo del estudio fue evaluar la incidencia de alteraciones hematológicas en pacientes con dengue. Métodos Se incluyeron retrospectivamente 64 pacientes, 14 embarazadas, con diagnóstico de dengue en los Hospitales Universitario de Monterrey y Civil Nuevo de Guadalajara, de enero de 2014 a diciembre de 2017. Resultados El dato clínico más común en el grupo general fue cefalea y dolor retroocular en 53 pacientes (83%), seguido de la fiebre, que se presentó en 12 pacientes embarazadas (86%). La mediana de cuenta plaquetaria en el grupo general fue de 51.4x103/pl, además, se encontró trombocitopenia en el 88% de los pacientes, mientras que en las pacientes embarazadas fue de 141.1 x103/pl, con trombocitopenia en 57% de ellas (p=0.002). La recuperación plaquetaria ocurrió en 7 días en el grupo general y 4.5 días en las pacientes embarazadas. Conclusiones Contrario a lo reportado en la literatura, las pacientes embarazadas presentaron una menor incidencia de trombocitopenia y una mayor cuenta plaquetaria, al momento del diagnóstico sin impacto en mortalidad materna ni en el curso del embarazo.(AU)

ABSTRACT Objective Dengue is a generally self-limited viral disease, considered a public health problem in Mexico. It can be accompanied by laboratory alterations such as neutropenia, lymphopenia and thrombocytopenia. The objective of the study was to evaluate the incidence of hematological alterations in patients with dengue. Methods We retrospectively included 64 patients, including 14 pregnant women, with a diagnosis of dengue at the Hospital Universitario de Monterrey and Civil Nuevo de Guadalajara from January 2014 to December 2017. Results The most common clinical symptom in the general group was headache and retro-ocular pain in 53 patients (83%), while in pregnant patients it was fever in 12 patients (86%). The median platelet count in the general group was 51.4x103/ μ!, with thrombocytopenia in 88% of patients, while in pregnant patients it was 141.1 x103/ with thrombocytopenia in 57% of patients (p=0.002). Platelet recovery was achieved in 7 days in the general group and 4.5 days in pregnant patients. Conclusions Contrary to that reported in the literature, pregnant patients had a lower incidence of thrombocytopenia and a higher platelet count at time of diagnosis without impact on maternal mortality or in the course of pregnancy.(AU)

[Dengue during pregnancy, less incidence of thrombocytopenia than in general population]. / Dengue durante el embarazo, menor incidencia de trombocitopenia que en la población general.

OBJECTIVE: Dengue is a generally self-limited viral disease, considered a public health problem in Mexico. It can be accompanied by laboratory alterations such as neutropenia, lymphopenia and thrombocytopenia. The objective of the study was to evaluate the incidence of hematological alterations in patients with dengue. METHODS: We retrospectively included 64 patients, including 14 pregnant women, with a diagnosis of dengue at the Hospital Universitario de Monterrey and Civil Nuevo de Guadalajara from January 2014 to December 2017. RESULTS: The most common clinical symptom in the general group was headache and retro-ocular pain in 53 patients (83%), while in pregnant patients it was fever in 12 patients (86%). The median platelet count in the general group was 51.4x103/ µ!, with thrombocytopenia in 88% of patients, while in pregnant patients it was 141.1 x103/ with thrombocytopenia in 57% of patients (p=0.002). Platelet recovery was achieved in 7 days in the general group and 4.5 days in pregnant patients. CONCLUSIONS: Contrary to that reported in the literature, pregnant patients had a lower incidence of thrombocytopenia and a higher platelet count at time of diagnosis without impact on maternal mortality or in the course of pregnancy.

OBJETIVO: El dengue es una enfermedad viral generalmente autolimitada, que en México se considera un problema de salud pública. Puede acompañarse de alteraciones de laboratorio como neutropenia, linfopenia y trombocitopenia. El objetivo del estudio fue evaluar la incidencia de alteraciones hematológicas en pacientes con dengue. MÉTODOS: Se incluyeron retrospectivamente 64 pacientes, 14 embarazadas, con diagnóstico de dengue en los Hospitales Universitario de Monterrey y Civil Nuevo de Guadalajara, de enero de 2014 a diciembre de 2017. RESULTADOS: El dato clínico más común en el grupo general fue cefalea y dolor retroocular en 53 pacientes (83%), seguido de la fiebre, que se presentó en 12 pacientes embarazadas (86%). La mediana de cuenta plaquetaria en el grupo general fue de 51.4x103/pl, además, se encontró trombocitopenia en el 88% de los pacientes, mientras que en las pacientes embarazadas fue de 141.1 x103/pl, con trombocitopenia en 57% de ellas (p=0.002). La recuperación plaquetaria ocurrió en 7 días en el grupo general y 4.5 días en las pacientes embarazadas. CONCLUSIONES: Contrario a lo reportado en la literatura, las pacientes embarazadas presentaron una menor incidencia de trombocitopenia y una mayor cuenta plaquetaria, al momento del diagnóstico sin impacto en mortalidad materna ni en el curso del embarazo.

Cytokines in cerebrospinal fluid of patients with schizophrenia spectrum disorders: New data and an updated meta-analysis.

Few studies have been conducted examining cytokines in cerebrospinal fluid of patients compared to healthy volunteers. The goals of this study were: 1) to report original data detailing cytokine levels in the cerebrospinal fluid (CSF) of 10 patients with a schizophrenia spectrum disorder (SSD) diagnosis and 10 healthy controls and 2) to conduct a meta-analysis of the available data on cytokine levels in the CSF of patients with SSD compared to healthy controls, including our new data. Cytokine concentrations were measured using the Q-plex Human Cytokine Screen array in CSF of 10 patients with SSD and 10 healthy volunteers. For the meta-analysis, an electronic PubMed and Google Scholar search without restrictions was conducted for articles that reported on cytokine levels in CSF in patients with an SSD compared to healthy controls. Our original data revealed statistically significant increases in levels of interleukin-8 (IL-8) and interleukin-1 beta (IL-1ß) in the CSF of patients with an SSD compared to healthy volunteers. Our meta-analysis showed statistically significant increases in interleukin-6 (IL-6) and IL-8 in patients compared to healthy volunteers. Effect sizes between treated and untreated patients for IL-6 were of similar magnitude. However, IL-6 levels were higher in early stage schizophrenia patients compared to chronic schizophrenia patients. Studies with larger sample sizes, comprehensive assessments and ideally in the context of a randomized controlled intervention to minimize the impact of confounding factors are needed to fully understand the role of cytokines and inflammatory markers in the pathophysiology and treatment of schizophrenia.

Cadaveric and Ultrasonographic Validation of Needling Placement in the Cervical Multifidus Muscle.

OBJECTIVE: The aim of this study was to determine if a needle is able to reach the cervical multifidus during the application of dry needling or acupuncture. METHODS: Dry needling and ultrasound imaging of cervical multifidi was conducted on 5 patients (age: 32 ± 5 years) with mechanical neck pain and on 2 fresh cadavers (age: 64 ± 1 years). Dry needling was done using a needle of 40 mm in length inserted perpendicular to the skin about 1 cm lateral to the spinous process at C3-C4. The needle was advanced from a posterior to anterior direction into the cervical multifidus with a slight inferior-medial angle (approximately 10°) to reach the vertebra lamina. For the cadaveric study, the multifidus was isolated by carefully resecting the superficial posterior cervical muscles: trapezius, splenius, and semispinalis. For the ultrasonographic study, a convex transducer was placed transversely over C3-C4 after the insertion of the needle into the muscle. RESULTS: The results of both the cadaveric and ultrasonic studies found that the needle does pierce the cervical multifidus muscle during insertion and that the tip of the needle rests properly against the vertebral laminae, thereby guarding the sensitive underlying spinal structures from damage. CONCLUSION: This anatomical and ultrasound imaging study supports that dry needling of the cervical multifidus could be conducted clinically.