Predictive markers for clinical outcomes in a cohort of diabetic patients hospitalized for COVID-19.

INTRODUCTION: The role of glycemic control, both prior and during hospitalization, on mortality from COVID-19 in diabetic patients is debated. Furthermore, it is not clear whether hyperglycemia has a direct effect or requires inflammatory mechanisms. OBJECTIVE: To identify predictors of clinical outcomes (in-hospital mortality, length of hospitalization, respiratory failure, need for intensive care), considering hyperglycemia, inflammation markers and clinical history. METHODS: Retrospective observational study of 291 diabetic patients hospitalized with COVID-19 in the Spedali Civili di Brescia from February 1th 2020 to March 31th 2021, with also outpatient electronic records. Glucose, inflammatory parameters, creatinine were collected within 24 h after admission to the hospital. A causal mediation analysis allowed the estimation of the direct and indirect effects of hyperglycemia on mortality. RESULTS: Glucose at admission ≥ 165 mg/dL and reduced renal function were associated with an increased risk of in-hospital mortality and length of hospitalization (all p < 0.001), while an increase in inflammatory parameters was significantly associated with an increased risk of all outcomes. High basophil count was associated with reduced mortality (p < 0.001). Hyperglycemia had a direct effect on mortality (p < 0.001); the indirect, through inflammatory markers, was significant only for absolute neutrophil count, C-Reactive protein and procalcitonin (p = 0.007, p = 0.029, p = 0.042). Patients with microvascular complications and with chronic kidney disease showed higher mortality (p = 0.03, p = 0.01). CONCLUSIONS: Hyperglycemia at admission, renal function and inflammatory parameters were found to be predictors of in-hospital mortality, while an increased basophil count was protective. Hyperglycemia had a direct effect on mortality, the indirect effect was only through few markers and markedly lower than the direct one.

Predictors of bone responsiveness to growth hormone (GH) replacement in adult GH-deficient patients.

Growth hormone (GH) replacement in adulthood results in variable bone responses as a function of the gonadic hormonal milieu. We performed a retrospective analysis of a large cohort of adult males and females with confirmed GH deficiency (GHD) prior to treatment and during 3 years of replacement therapy. Potential confounders and effect modifiers were taken into account. Sixty-four adult patients with GHD (20 females and 44 males; mean age 34 years, range 18-64) were included in the analysis. GH replacement induced a different effect on bone in males compared to females. Bone mineral content increased in males and decreased in females at the lumbar spine, total femur, and femoral neck; bone mineral density showed a similar trend at the lumbar spine and femoral neck. There was no significant gender difference in bone area at any measured bone site. In both sexes we observed a similar trend for serum markers of bone remodeling. Sex predicted bone outcome on multivariate analysis, as did age, onset of GHD (childhood/adulthood), pretreatment bone mass, baseline body mass index (BMI), and BMI change during GH replacement. Serum IGF-I levels during treatment did not show any relationship with bone outcome at any measured site. This study confirms that bone responsiveness to GH replacement in adult GHD varies as a function of sex even after controlling for potential confounders and highlights the importance of other cofactors that may affect the interaction between GH replacement therapy and bone remodeling.

A Prospective Study for Introducing Insulin Pens and Safety Needles in a Hospital Setting. The SANITHY Study.

BACKGROUND: to assess costs and safety of insulin pen devices and safety needles as compared to vial/syringes in hospitalized patients requiring insulin therapy in a General Hospital in Northern Italy. MATERIALS AND METHODS: in a prospective 9-month study, consecutive patients admitted to three Hospital Units received insulin therapy through either a traditional disposable syringe method, or pen/safety needles with dual-ended protection, or disposable safety syringes. We compared the median direct (insulin and devices) and indirect (insulin supply at discharge, insulin wastage) costs of a 10-day in-hospital insulin treatment in the 3 study groups, additionally accounting for the costs related to the observed needlestick injury rate. Patients' safety during in-hospital stay (hypo- and hyperglycemia episodes) and satisfaction were also assessed. RESULTS: N=360 patients (55% men, mean age 75.6 years, 57% with DM since ≥10 years) were recruited in the study. Insulin pens had higher median direct cost than both traditional syringes (43 vs. 18 ε/patient, p<.0001) and safety syringes (21.5 ε/patient, p<.0001). However, when also indirect and injuries costs were taken into account, the estimated savings for using pens over traditional syringes were as high as 32 ε/patient (45.8 vs. 77.6 ε/patient, p-value <.0001). No differences in patients' safety were observed. 74% and 12% of patients using pens and syringes would like to continue the method at home, respectively (p<0.0001). DISCUSSION: A selective use of individual pre-filled pens/safety needles for patients who are likely to continue insulin therapy at home may strongly reduce hospital diabetes treatment related costs.

Time course of hypothalamic-pituitary deficiency in adults receiving cranial radiotherapy for primary extrasellar brain tumors.

BACKGROUND: No longitudinal data on hypothalamic-pituitary (HP) function are available in patients who had received cranial radiation therapy (CRT) for primary extrasellar brain tumors (PBT). PURPOSE: To investigate the effects of CRT on HP function in adults with PBT. PATIENTS AND METHODS: Twenty-six adults irradiated for PBT and six CRT naive controls were studied. CRT was delivered with 6 MV X-ray by a linear accelerator (2 Gy fraction schedule). Gross Tumor Volume (GTV) excluded the HP region that was contoured on the planning CT. Median dose to the HP region was 41.8 Gy (IQR: 30.7-49.8). RESULTS: All controls maintained normal HP function. Hypopituitarism developed in 38% of CRT patients (GH deficiency 29%, ACTH 22%, TSH 14%, gonadotropin 4%, no abnormal prolactin level or diabetes insipidus). All HP failures occurred within 32 months after CRT. CONCLUSIONS: Adults undergoing CRT for PBT are at increased risk for HP dysfunction within 3 years from CRT. Endocrine surveillance is recommended also in adults patients exposed to CRT for primary brain tumors distant from HP region.

Treatment of thyroid-associated orbitopathy with rituximab--a novel therapy for an old disease: case report and literature review.

OBJECTIVE: To report the use of rituximab to treat thyroid-associated orbitopathy (TAO) in a patient with a concomitant B-cell organ-specific autoimmune disorder-the stiff person syndrome (SPS). METHODS: We present a case report and a review of the related literature. RESULTS: A 62-year-old man with SPS, latent autoimmune diabetes of the adult, and Graves-Basedow disease was referred to our medical center because of bilateral TAO. An ophthalmologic examination documented asymmetric bilateral NOSPECS (N = no signs or symptoms; O = only signs, no symptoms; S = soft tissue involvement; P = proptosis; E = extraocular muscle involvement; C = corneal involvement; and S = sight loss) class IV TAO (left eye>right eye) with a clinical activity score of 5 on a scale of 7. Magnetic resonance imaging of the orbits documented bilateral exophthalmos (left eye>right eye) due to retrobulbar fibroadipose infiltration, bilateral increase of extrinsic ocular muscle thickness, and enhancement of the left inferior rectus muscle on T2-weighted sequences. Because of concomitant incapacitating SPS and diet-controlled latent autoimmune diabetes of the adult, we excluded long-term corticosteroid therapy as an option and considered the use of rituximab, a mouse-human chimeric monoclonal antibody targeting the CD20 protein on pre-B and mature B lymphocytes. Rituximab was administered in accordance with the protocol for rheumatoid arthritis. During the subsequent 4 months, clinical signs and symptoms of TAO dramatically resolved (clinical activity score = 0 of 7) with a sustained improvement of the spastic paraparesis. The glutamic acid decarboxylase antibody titer remained high, and glycemic control and first-phase insulin secretion did not change. CONCLUSION: Treatment of active TAO with rituximab should be considered when standard intravenous pulse glucocorticoid treatment is contraindicated or ineffective and when SPS or other organ-specific autoimmune disorders with involvement of humoral autoimmunity are present, inasmuch as more than 1 disease may benefit from the use of this chimeric monoclonal antibody.

Long-term effects of growth hormone replacement therapy on thyroid function in adults with growth hormone deficiency.

BACKGROUND: Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH). METHODS: The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 microg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels. RESULTS: During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (microg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years. CONCLUSION: We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.