Missing Care: the Initial Impact of the COVID-19 Pandemic on CKD Care Delivery

BackgroundChronic kidney disease (CKD) is a common condition with adverse health outcomes addressable by early disease management. The impact of the COVID-19 pandemic on care utilization for the CKD population is unknown.ObjectiveTo examine pandemic CKD care and identify factors associated with a high care deficit.DesignRetrospective observational studyParticipants248,898 insured individuals (95% Medicare Advantage, 5% commercial) with stage G3–G4 CKD in 2018Main MeasuresPredicted (based on the pre-pandemic period of January 1, 2019–February 28, 2020) to observed per-member monthly face-to-face and telehealth encounters, laboratory testing, and proportion of days covered (PDC) for medications, evaluated during the early (March 1, 2020–June 30, 2020), pre-vaccine (July 1, 2020–December 31, 2020), and late (January 2021–August 2021) periods and overall.Key ResultsIn-person encounters fell by 24.1% during the pandemic overall; this was mitigated by a 14.2% increase in telehealth encounters, resulting in a cumulative observed utilization deficit of 10% relative to predicted. These reductions were greatest in the early pandemic period, with a 19.8% cumulative deficit. PDC progressively decreased during the pandemic (range 9–20% overall reduction), with the greatest reductions in hypertension and diabetes medicines. CKD laboratory monitoring was also reduced (range 11.8–43.3%). Individuals of younger age (OR 1.63, 95% CI 1.16, 2.28), with commercial insurance (1.43, 95% CI 1.25, 1.63), residing in the Southern US (OR 1.17, 95% CI 1.14, 1.21), and with stage G4 CKD (OR 1.21, 95% CI 1.17, 1.26) had greater odds of a higher care deficit overall.ConclusionsThe early COVID-19 pandemic resulted in a marked decline of healthcare services for individuals with CKD, with an incomplete recovery during the later pandemic. Increased telehealth use partially compensated for this deficit. The downstream impact of CKD care reduction on health outcomes requires further study, as does evaluation of effective care delivery models for this population.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-022-07805-w.KEY WORDS: chronic kidney disease, COVID-19, epidemiology     

Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.     

Hedgehog signaling and laminin play unique and synergistic roles in muscle development

Hedgehog (Hh) signaling and laminin‐111, a basement membrane protein, are required for early muscle development. Hh signaling specifies different populations of muscle fibers and laminin‐111 is critical for early muscle morphogenesis. However, additional requirements for Hh signaling and laminin during later phases of muscle development are not known. Furthermore, interactions between Hh signaling and laminin in this context are unknown. We used laminin gamma1 mutant zebrafish and cyclopamine to block Hh signal transduction separately and in combination to investigate their functions and interactions. We found that both Hh signaling and laminin are required for normal myosin chain expression. In addition, Hh signaling and laminin act synergistically during fast‐twitch fiber elongation: fast muscle cells do not elongate in embryos deficient for both Hh signaling and laminin. Finally, we present evidence that suggests that Hh signaling is indirectly required via slow fiber specification for recovery of fast fiber elongation in laminin gamma1 mutant embryos. Developmental Dynamics 239:905–913, 2010. © 2010 Wiley‐Liss, Inc.     

Spastic Paraplegia, Optic Atrophy, and Neuropathy: New Observations, Locus Refinement, and Exclusion of Candidate Genes

SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with marker D11S1889). Three genes located in this newly defined critical region were sequenced, but no pathogenic mutation was detected. The gene responsible for SPOAN remains elusive.     

Type I interferons have opposing effects during the emergence and recovery phases of colitis

The contribution of the innate immune system to inflammatory bowel disease (IBD) is under intensive investigation. Research in animal models has demonstrated that type I interferons (IFN‐Is) protect from IBD. In contrast, studies of patients with IBD have produced conflicting results concerning the therapeutic potential of IFN‐Is. Here, we present data suggesting that IFN‐Is play dual roles as regulators of intestinal inflammation in dextran sodium sulfate (DSS)‐treated C57BL/6 mice. Though IFN‐Is reduced acute intestinal damage and the abundance of colitis‐associated intestinal bacteria caused by treatment with a high dose of DSS, they also inhibited the resolution of inflammation after DSS treatment. IFN‐Is played an anti‐inflammatory role by suppressing the release of IL‐1β from the colon MHC class II⁺ cells. Consistently, IL‐1 receptor blockade reduced the severity of inflammation in IFN‐I receptor‐deficient mice and myeloid cell‐restricted ablation of the IFN‐I receptor was detrimental. The proinflammatory role of IFN‐Is during recovery from DSS treatment was caused by IFN‐I‐dependent cell apoptosis as well as an increase in chemokine production and infiltrating inflammatory monocytes and neutrophils. Thus, IFN‐Is play opposing roles in specific phases of intestinal injury and inflammation, which may be important for guiding treatment strategies in patients.     

Infrared LED light therapy influences the expression of fibronectin and tenascin in skin wounds of malnourished rats—A preliminary study

The aim of this investigation was to evaluate the effect of infrared (λ 846 ± 20 nm) LED irradiation on the expression profile of the extracellular matrix protein components, tenascin and fibronectin on skin wounds induced in well nourished and malnourished rats. Eighteen albino rats (21 days old) were randomly divided into a well-nourished group (standard diet) and a malnourished group (regional basic diet). After receiving the diet for 70 days, skin wounds were created and the animals were subdivided into three groups: well-nourished control (n = 6), malnourished control (n = 6), and malnourished + LED irradiated (λ 846 ± 20 nm, 100 mW, 4 J/cm²) (n = 6). The animals were sacrificed 3 and 7 days after injury and histological sections were immunostained for both proteins. They were examined for the presence, intensity, distribution and pattern of immunolabeling. At 3 days, the distribution of tenascin was shown to be greater in the wound bed of malnourished animals compared to the well-nourished group. The intensity and distribution of tenascin was shown to be lower in the malnourished LED irradiated group compared to the malnourished control. There was a significant difference regarding the presence of fibronectin in the malnourished and well-nourished groups after 7 days (p = 0.03). The intensity of fibronectin was slight (100%) in the irradiated group and moderate to intense in the malnourished control group. The results of the present study indicate that infrared LED irradiation modulates positively the expression of tenascin and particularly fibronectin.     

Distinct Leishmania braziliensis isolates induce different paces of chemokine expression patterns

Inflammatory events during Leishmania braziliensis infection in mice were investigated. Large lesions were directly correlated with the inflammatory reaction but not with parasite burden. Different L. braziliensis strains induce different paces of chemokine expression patterns, leading to diverse cell recruitment and differential inflammatory responses.